Psychopharmacology With Children and Adolescents
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CHAPTERNINEMedicatingChildren.docxCHAPTER NINE Medicating Children
This chapter is divided into seven sections. Section One is an overview that discusses current trends in medicating children, problems the trends cause, and directions for the future. It also discusses developmental issues. Section Two focuses on stimulant medication and the diagnosis of attention deficit hyperactivity disorder (ADHD). Section Three focuses on research on combined interventions and particularly the Multimodal Treatment Study (MTA study) of Children with ADHD. Section Four focuses on children taking mood stabilizers. Section Five focuses on antipsychotics and children. Sections Six and Seven focus on anxiolytics and antidepressants in children, respectively.
SECTION ONE: PERSPECTIVES, DILEMMAS, AND FUTURE PARADIGMS
Learning Objectives
· • Understand the problematic increase in psychotropic medications for children despite a dearth of evidence of the effectiveness of these drugs.
· • Have a general understanding of the impact of the FDA Modernization Act and the Best Pharmaceuticals Act for Children.
· • Be able to state the “developmental unknowns” associated with giving kids psychotropic medications.
Thus far, we have explored the medical model and psychological, cultural, and social perspectives as they relate to psychopharmacology. In this chapter, we demonstrate that using psychotropic medications with children and adolescents raises particular problems and concerns from several perspectives. As discussed in Chapter Three , we frequently see explanations and justifications from the medical model perspective used to reduce childhood disorders to chemical and genetic problems, excluding crucial consideration of environmental traumas, developmental foreclosures, or life stressors.
We explore child and adolescent psychopharmacology primarily from the medical model perspective but complement this approach with information from the other perspectives (psychological, cultural, and social). We set the stage by exploring the current status of the treatment of children and adolescents with mental and emotional disorders. This chapter is structured differently from the others in this book. We begin by discussing the context from the social and cultural perspectives and the problems with prescribing psychotropic medications to children. Then we cover an introduction to stimulants used to treat symptoms of ADHD. Finally, we give the status of their current use since the last edition of the book if that is possible.
THE COMPLEX STATE OF THERAPY
Dr. Frank O'Dell, Professor Emeritus of Counseling in the College of Education and Human Services at Cleveland State University, has argued in all his lectures on counseling children and adolescents that the United States is an “anti-kid” society (Personal Communication, 2001). By that he means fewer
and fewer therapists and psychiatrists choose to treat or continue to work with children in counseling. To support his argument, O'Dell points out that resources for children, including the number of hospital beds in mental health wards for children, have been shrinking. He believes the rules of managed care companies, dwindling personnel resources, and increasing difficulty in working with parents or guardians and their struggling children all contribute to the current trend. This has been a problem for at least 45 years. The American Academy of Child & Adolescent Psychiatry (AACAP) (2001) summarized the following facts, which support O'Dell's assertion, indicating little has changed:
· • There is a dearth of child psychiatrists. Satcher (2001) stated further that many barriers remain that prevent children, teenagers, and their parents from seeking help from the small number of specially trained professionals who are available and that places a burden on pediatricians, family physicians, and other gatekeepers to identify children for referral and treatment decisions ( U.S. Department of Health and Human Services, 2001 ).
· • The AACAP's report projected that between 1995 and 2020, the need for child and adolescent psychiatrists will increase by 120%, whereas the need for general psychiatry is projected to increase at 22% for the adult population.
· • McCarty, Russo, and Rossman (2011) demonstrated that only 13% of youth with suicidal behaviors and ideation receive mental health services.
· • In November 2010, the Coalition for Juvenile Justice estimated that up to 75% of teenagers in the juvenile justice system nationwide have a diagnosable mental disorder, and these numbers continue.
· • One in 10 children suffers from mental illnesses severe enough to impair development. Fewer than 1 in 5 children get treatment for mental illness.
The U.S. Department of Health and Human Services (2001) concluded that burgeoning numbers of children are suffering needlessly because their emotional, behavioral, and developmental needs are not being met by the institutions and systems created to care for them. As the number of children and adolescents needing psychological treatment rises and the number of service providers falls, the primary treatment modality becomes psychotropic medications rather than therapy. Imagine if you were a parent of one of these children.
Debner (2001a) reported that in a one-year period, 350 children needing hospitalization were turned away from hospitals in the Boston area. This phenomenon is occurring in most major U.S. cities and is exacerbated by hospitals holding onto children who are ready to be discharged, because there is no suitable placement for them. In another article, Debner (2001b) noted that the chief pediatricians from the five major academic health centers in Massachusetts indicated there is a serious crisis in psychiatric services for youth in the state. The doctors said they and their staffs could not find appropriate therapy and other mental health services for mentally ill children. As a result, many such children deteriorate to the point of crisis. Thomas and Holzer (2006) reported that America suffers from a serious longterm shortage of child psychiatrists that is taking a toll on young people, their parents, and their doctors. It is further recognized that the demand for psychotropic drugs is intense in spite of dangerous side effects.
The Washington Post (2002) published an article about a woman who desperately needed a psychiatric evaluation for her teenage daughter and who left 36 phone messages for various psychiatrists. She received only four replies. All the replies were from practitioners who refused to take the case because they did not treat adolescents. The article further detailed how, more and more, in-network providers (clinicians) prefer not to take patients covered by managed care plans, because reimbursements are so low and restrictions so numerous. The article also highlighted the disparity and arguments between the treating professionals and spokespeople from managed care companies. It is more than fair to say that desperate parents and anguished children are caught in the political policy dilemma over the cost and reimbursement of mental health treatment for children and adolescents.
Since the first edition of this book, there has been a movement to train more primary care physicians in pediatric mental health services to try to address the shortage of pediatric mental health professionals. Aupont et al. (2013) describe a model called Targeted Child Psychiatric Services designed for primary care physicians as well as child psychiatrists. This was associated with improved access to the child psychiatric services that exist, helped identify optimal care settings for patients and helped pediatricians be more likely to accept a patient back after that patient had been under psychiatric care.
Another problematic topic is who dispenses medications in schools. Most states have a policy on this and many states have a Nurse Delegated Medication Administration program ( Ryan, Katsiyannis, Losinski, Reid, & Ellis, 2014 ). Most standardized curricula include trainings of approximately 30 hours with 8-hour updates every two years or so. These are by and large directed by professional nurses ( Spector & Doherty, 2007 ). Nationwide lists of states and their programs can be found at http://www.nasbe.org/healthy_schools/hs/bytopics.php?topicid=4110&catExpand=acdnbtm_catD and http://www.healthinschools.org/health-in-schools/health-services/schoolhealth-services/school-health-issues/medicationmanagement/state-policies-on-administration-of-medication-in-schools.aspx .
THE EXPLOSION OF PSYCHOTROPIC MEDICATION PRESCRIPTIONS FOR CHILDREN AND ADOLESCENTS
With diminishing psychological supports for children and adolescents, using psychotropic medications with them has become the treatment of choice, even though the majority of medications used with them lack FDA “on-label” approval for them ( Werry, 1999 ). Researchers currently estimate that between 7.5 and 14 million children in the United States experience significant mental health problems ( Riddle, Kastelic, & Frosch, 2001 ; Wozniak, Biederman, Spencer, & Wilens, 1997 ). These statistics vary a little from Satcher (2001) , cited earlier; clearly, millions of children in this country require mental health services. Children are increasingly prescribed psychotropic medications as part of their treatment; in many cases, the medications replace the therapy ( Jensen et al., 1999 ; Phelps, Brown, & Power, 2002 ). Given the explosion in the use of psychotropic medication with children, it is important also to note that this population has been excluded from clinical trials of these drugs. Hence, decisions about juvenile medication obviously rest more on extrapolation of adult data to children and adolescents than on direct research and evaluation of the safety and efficacy of psychotropic medication with children ( Riddle et al., 2001 ; Vitiello & Jensen, 1997 ).
Coyle (2000) indicated that 80% of all medications prescribed to children and adolescents in the United States have not been studied for the safety and benefit of these populations. As of 2011, The National Institutes of Health indicated that methylphenidate, lithium, all atypical antipsychotics, lorazepam, and amitriptyline were still on the highest priority list of needs in Pediatric Therapeutics of drugs to be studied in pediatric populations.
Even though there is a black box warning related to the risk of increased suicidality in children and adolescents prescribed SSRIs and SNRIs, the use of these psychotropic agents has increased with children and adolescents ( Markowitz & Cuellar, 2007 ). The trend in treating children and adolescents with off-label psychotropic medications, mostly in lieu of counseling and psychotherapy, has triggered concern both in the general public and the mental health community. Coyle (2000) , Furman (1993) , and Zito ( Zito et al., 2000 , 2003 ) argue that there is little or no evidence to support psychotropic drug use with very young children and conclude that such treatment could have harmful psychological, developmental, and physical effects. In a multinational study, American youths were three times more likely to be on an antidepressant medication than their peers in Denmark, Germany, and the Netherlands ( Zito et al., 2006 ). In 2010, the pharmaceutical companies research protocols were really challenged when uncovered pharmaceutical studies on many highly utilized
psychotropics were found to be no more efficacious than the placebo. In fact, the second author has personal communications with several psychiatrists in their fourth or fifth decade of practice who question the overall effectiveness of psychopharmacology with patients, especially children (Ramirez, Personal Communication, 2014).
In another multinational study, Zito et al. (2008) found that the annual prevalence of youth taking psychotropic medication was threefold greater in the United States than in the Netherlands and Germany. The atypical antipsychotics represented 5% of antipsychotic use in Germany but 66% in the United States. Interestingly, though, anxiolytics were twice as common in Dutch youth than as in U.S. or German youth.
With proper research, mental health professionals may be able to head off disasters such as aspirin precipitating Reye's syndrome or valproate leading to sudden death in infants ( Riddle et al., 2001 ). Given the lack of knowledge about the long-term and adverse effects of psychotropic medication on children, it is crucial that mental health clinicians be alert to the impact of these drugs on children and advocate for youth when the evidence that such drugs would be helpful is questionable ( Ingersoll, Bauer, & Burns, 2004 ). At this point, we would like to introduce a case that highlights many of the treatment and medication dilemmas children and adolescents encounter.
THE CASE OF PHILLIP
Phillip is a 7-year-old first-grader from a singleparent home. His mother is on public assistance, and he is the oldest of four boys. Although some of the details of his developmental history are sparse, Phillip began to exhibit impulse control problems at the age of 2 years and 4 months, shortly after his father moved out of the house. He was hypervigilant, easily distractible, aggressive with his younger sibling, and frequently irritable. Initially, his mother believed he was going through a stage of rebelliousness, but after several months she became concerned about his behavior and mentioned this to the pediatrician. After a brief examination, the pediatrician indicated that Phillip was likely suffering from ADHD and recommended against medication unless his behavior got too out of control at home. However, she felt he would need a course of methylphenidate/ Ritalin, a prescription stimulant, once he began preschool. Phillip's mother accepted this recommendation and planned to have him evaluated when he began preschool. Phillip's behavior improved slightly over the next several months, without therapy or psychotropic medication.
When he began preschool, it took only a few days before all his active symptoms returned. After observing him for several weeks, the teacher recommended to Phillip's mother that he see a physician to be assessed for a stimulant medication. After the evaluation, the physician prescribed 10 mg of methylphenidate/Ritalin daily for Phillip. Methylphenidate/Ritlain is one of the most common stimulants used for symptoms of ADHD in children. It is intended to reduce inattentiveness, distractibility, impulsivity, and motor hyperactivity, with a goal of improved academic productivity. Phillip's symptoms slightly improved over the next eight weeks, but his aggressive behavior toward other children increased. Phillip's mother noticed more unpredictable behavior at home, as well as sleeplessness and restlessness followed by long periods of lethargy. She took him back to his physician, who referred them to a psychiatrist. The psychiatrist, after a three-session assessment, diagnosed Bipolar I (BPI) Disorder, took him off the methylphenidate/Ritalin, and prescribed 50 mg of carbamazepine/Tegretol daily and 0.01 mg of clonazepam/ Klonopin. The carbamazepine/Tegretol was used to reduce his manic symptoms. This antiseizure medication has over time been found very effective with Bipolar Disorder ( Phelps et al., 2002 ).
The clonazepam/Klonopin was used to address Phillip's anxious and agitated symptoms. This antianxiety medication often relaxes children and reduces anxiety without inducing sleep.
Many of Phillip's symptoms diminished, but his mother noticed both a sluggishness and apathy in him that were new. Over the course of the next year, Phillip's teacher addressed several of his learning and cognitive processing problems. Up to this
point, the focus of Phillip's treatment had been psychopharmacologic. No psychosocial interventions were given to Phillip, as is often the case ( Phelps et al., 2002 ). No one seemed to have any awareness or discussion about the optimal level of medication for Phillip, and there was no referral for a psychosocial assessment. As his symptoms worsened, he was evaluated by a psychiatrist schooled in prescribing adult psychotropic medications off label to children. Finally, Phillip's mother took him to see a therapist, who focused on Phillip's attachment issues, his phobic anxiety triggered by sudden loss or the anticipation of sudden loss, and his physiologic symptoms, which the therapist considered powerful side effects of the pharmacologic therapy.
Analysis of Phillip's Case
Analyzing the case, Phillip was treated by pharmacology in the medical model method and rational thinking centered on pharmacology dominated the case. The combination of methylphenidate/Ritalin and carbamazepine/Tegretol on Phillip's system was supposed to reduce some of his externalizing symptoms in the constellation of ADHD or Bipolar I disorders, but the psychological aspects of his personality were ignored. Not until much later in the course of his illness did Phillip get some assistance in those domains. Culturally, Phillip's mother had little power in society and was torn between accepting the opinion of the medical experts, and watching the negative impact the medications were having on her son. As mental health professionals, we need to understand the medical psychiatry's rapid efforts to address most disorders of childhood and adolescents with psychotropic medication. Far too often, medicating professionals view talk therapy and other psychosocial interventions as ineffective and second rate. Because medical professionals hold more power in our society than mental health professionals, their medical opinions are frequently given more weight. Today, psychiatrists burdened by enormous caseloads are open to what is known as split-treatment, a joint effort by the mental health professional and psychiatrist to plan and integrate treatment and be vigilant for client manipulation. We must integrate care into a larger model of treatment that addresses each of the four perspectives equally and where mental health professionals' opinions on mental health treatment are given more weight. In addition, the power of pharmaceutical companies must be monitored. Bodenheimer (2000) has documented numerous cases where companies prevented important research findings from being published because they were not favorable regarding the compounds being tested. To what extent may such situations affect clients like Phillip? This will be discussed later in the chapter.
Remember, Phillip was in the 4 to 7 age range when he began treatment. Coyle (2000) comments that there is “no empirical evidence to support psychotropic drug treatment in very young children and that such treatment could have deleterious effects on the developing brain” (p. 1060). Furman (1993) posited that psychiatrists in the United States are recklessly “out of control” in prescribing methylphenidate/ Ritalin and other stimulants for children, in contrast to the extreme caution that physicians in almost all European countries use in recommending this treatment approach. With the increasing trend to medicate a younger and younger population ( Zito et al., 2000 ), mental health professionals not only need to understand the impact and therapeutic effectiveness of these medications, but also their limitations and potential for harming children.
THE MEDICATION OF CHILDREN AND THE FEDERAL LAWS
As we have noted in previous chapters, the laws of the land hold great influence over cultural and social paradigms. To a large extent, laws are the result of a dynamic interaction of forces that influence other areas such as socioeconomic status and the fiscal systems of a society. Socioeconomic status and fiscal systems shape laws in very powerful ways, and people with financial resources are able to buy influence with lawmakers. This is nothing new, but bears stating in this chapter. Although recent legislation has been introduced to address
the many problems of prescribing psychotropic medications for children, most such laws require only voluntary testing of psychotropic drugs, diminishing any real impact. In this section, we summarize recent laws and comment on them, beginning with a summary in Table 9.1 .
TABLE 9.1 Major Emphases of Recent Legislation on Pediatric Pharmacology
© Cengage Learning®
FDA Modernization Act
Buck (2000) traced the unfolding need for greater specific labeling of drugs used with patients less than 18 years of age. The burgeoning use of almost all drugs approved for children by the FDA compelled pediatric health care providers to use these drugs off label without a clear knowledge of dosing, administration, or adverse-effect information. In 1992, the FDA took steps to improve both pediatric labeling and research, which resulted in support for building a network of pharmacologic research by the National Institutes of Health (NIH). These efforts began to address the problem, and passage of the FDA Modernization Act (1997) for the first time set specific requirements to tighten regulations relating to pediatric pharmacology. This law encouraged pediatric labeling on drugs used widely with children and adolescents where the lack of labeling might lead to serious misuse. However, the FDA website (2013) warns that users of methylphenidate/ Ritalin may have an erection lasting many hours. This from an agency that still cannot conduct pediatric studies that evaluate the full impact of the drug on that population.
This law goes a long way toward recognizing the rights of children as patients, protecting their health, and assisting pediatric providers with essential information. Unfortunately, the law did not go far enough. Many practitioners and lawmakers felt the need for a comprehensive law to mandate pharmacologic research, monitor it, and further protect children.
The Best Pharmaceuticals for Children Act
On January 4, 2002, President George W. Bush signed Public Law Number 107-109, the Best Pharmaceuticals for Children Act ( Dodd, 2001 ), with the anticipation that it would address many of the dilemmas and controversies surrounding the eruption in use of pharmaceuticals for children. This law aims to initiate critical studies with pharmaceuticals already prescribed to a population for whom there exists little research, and it tightens the monitoring and development of new drugs released for children and adolescents. The law seeks to integrate viewpoints on medicating children with the medical, cultural, and social perspectives. Unfortunately, its most powerful provisions regarding the conduct of pharmaceutical companies are voluntary.
The Best Pharmaceuticals for Children Act (BPCA) has 19 sections that can be viewed at http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/ucm148011.htm ).
This law encourages voluntary pediatric studies of already marketed drugs, the so-called off-label psychotropic drugs in widespread use with children, and it creates a research fund for studying these drugs (see http://blogs.fda.gov/fdavoice/index.php/tag/best-pharmaceuticals-for-children-act-bpca/ ). Both efforts are critical to understanding the effectiveness and efficacy of psychotropic medications for children and adolescents. Further, the law establishes an ongoing program for the pediatric study of drugs, including a list of all drugs for which documentation is needed. This aspect of the law is monitored by the commissioner of the FDA and the director of the National Institutes of Health, who have the power to make written requests to pharmaceutical companies for pediatric studies. The law requires timely labeling changes for pediatric drugs under study.
As of this edition, the status of most pharmaceuticals for children and adolescents remains similar to what it was in 2006. There was the black-box effort with SSRIs and SNRIs, but they are prescribed at rates higher than in 2006 ( Cummings & Fristad, 2007 ) and most other psychotropics are used with children and adolescents to quiet anxiety, agitation, and rage.
However, the pharmaceutical companies continue to challenge the Pediatric Rule on all fronts and now it is 2014 and most important drugs for children have not been studied with a pediatric group. So goes the Pediatric Rule. On October 17, 2002, the U.S. District Court for the District of Columbia ruled that the FDA did not have the authority to issue the Pediatric Rule and has barred the FDA from enforcing it. The Pediatric Rule would have required timely pediatric studies and adequate labeling of all human drugs.
Child and Family Services Improvement Act
The Child and Family Services Improvement Act of 2011 (Public Law 112-34) includes new language that addresses the social-emotional and mental health of children who have been traumatized by maltreatment. State Child and Family Services Plans now have to include details about how emotional trauma associated with maltreatment and removal is addressed. They also have to describe how the use of psychotropic medications is monitored.
A WORD ON CROSS-CULTURAL PERSPECTIVES
Tseng (2003) proposed many variables and differences in prescribing psychotropic medications to children and adolescents from various cultures. He stressed that one must consider not only the physician's attitudes about treating people from different cultures, but also the patients' perspectives on how they feel about psychotropic medications. Thus, the giving and receiving of medications has many implications. This factor is greatly enhanced for children and adolescents, because the physician must not only communicate with the parents about the diagnosis and the psychotropic medications (neither of which may make sense in the parents' worldview) but must also weigh carefully the cultural issues that the family brings to treatment.
Tseng (2003) also addresses the enculturation issues of children. His research has described how not every culture emphasizes the fast-paced and often accelerated approach to growing up that characterizes the United States. Enculturation is defined as a process through which an individual, starting in early childhood, acquires a cultural system through the environment, particularly from parents, school, and so on. Some cultures, such as many Asian cultures, have a laid-back attitude toward babies and toddlers that is more indulgent. Yet later, they show a dramatic shift for these children, who, when they arrive at latency, the developmental period between the ages of 6 and 11 or 12, experience enormous pressure to be diligent and to achieve. Thus, as clinicians treat children and adolescents from all cultures, they need to reconsider cross-cultural adjustment and revise the psychosocial stages of Erikson (1968) , which depended on developmental understandings in a particular culture.
With the upsurge in the use of psychotropic medications, it is impossible to monitor the expected and unexpected adverse effects. Given the expanding knowledge of the varying developmental trajectories of children from other cultures, mental health practitioners and psychiatrists need to exercise further caution when prescribing psychotropic medications
for these children. Lin and Poland (1995) described in detail the remarkably large interindividual variability in drug responses and side effect profiles. This can be partially accounted for in differences of ethnicity and/or culture apart from physiological pace. Some cultures are very suspicious of medication and may delay the decision for more than a year.
Lin and Poland (1995) have made significant contributions to the understanding of cultural psychiatry and to the fact that genetic factors associated with individual and ethnic backgrounds contribute greatly to responses to medication in children, adolescents, and adults. Kirmayer and Ban (2013) note that cultural differences in self and personhood are equally important. All researchers we reviewed point to variations within the same ethnic group and variations among ethnic groups. This further complicates the integrative dilemma, which is how to view psychopharmacology and cases from the four perspectives outlined in Chapter One as well as consider important developmental lines and levels. Mental health professionals recognize that researchers have much to learn about psychopharmacology with children and adolescents, as shown by the research cited in this chapter. We need to integrate our growing understanding of cultural psychiatry with our limited understanding of how psychotropic medications work in children. The Best Pharmaceutical Act for Children (2002) provided for including in studies children from various racial and ethnic backgrounds. The law calls for studying the impact of medications on children of different cultures.
PSYCHOLOGICAL PERSPECTIVES OF CHILDREN AND ADOLESCENTS
Medicating children and adolescents for all types of psychological disorders is a solution that only reflects partial truth. The overt behaviors and symptom profile for which they receive medication may only mask the deeper psychological wounds of loss, trauma, abuse, sibling rivalry, neglect, sexual abuse, or gender conflict. Furman (2000) has indicated that if mental health professionals carefully examined the overuse of stimulants with children, they would discover a variety of conflicts and problems fueling the hyperactive behavior. These issues could include cruelty in the home, harsh toilet training, neglect, sexual abuse, delay in language development, and more.
Young children cannot address their inner conflicts without the help of a caring therapist and the modality of play therapy, yet far too often they are diagnosed with Bipolar I or ADHD and medicated in an attempt to quickly suppress their active symptoms. There should be far more effort to get the child to a therapist to uncover the underlying cause(s) of the child's anguish, but this requires resources that, at the time of this writing, lawmakers are not giving a high priority.
The American Academy of Pediatrics (2011) for ADHD makes clear that parent and teacher assessments at home and school, respectively, along with clinical review and examination by pediatrician or psychiatrist, often omit psychological assessment of the child by a mental health professional to rule out abuse, neglect, loss, sleeplessness, or other potential causes of hyperactivity or mania. In this protocol (the AAP guidance), the psychology and clinical history of the child are treated as unimportant. Many authors unfortunately support rapid assessment of ADHD children to speed up treatment with stimulant medication.
OPPOSITION TO THE CURRENT TREND OF MEDICATING
Opponents to exclusive medication treatment for ADHD, Bipolar I, and other conditions have pointed out significant regional variations in the amount of psychotropic medications prescribed to children and wide variations in regional diagnostic criteria for ADHD and other conditions ( Safer, Zito, & Fine, 1996 ; Wolraich, Hannah, Pinnock, Baumgaertel, & Brown, 1996 ). These variances have legislators and mental health advocates from various regions of the country clamoring for more judicious use of psychotropic medications with children, with more careful attention to the range of adverse effects from them, and a more formalized protocol for diagnosing ADHD, Bipolar I, and
other conditions. This protocol should go well beyond the traditional oral report from teacher to parent about a child's externalizing behavior. Opponents of psychotropic medication use in children call for a more specific and guided differential diagnosis of these disorders because the symptoms commonly overlap with Oppositional Defiant Disorder, Conduct Disorder, Major Depressive Disorder, various anxiety disorders, and many developmental disorders ( American Academy of Child and Adolescent Psychiatry, 2007 ; August, Realmuto, MacDonald, Nugent, & Crosby, 1996 ). Many researchers and practitioners still feel that ADHD in particular is a myth and that the explosion in use of the diagnosis renders differential diagnosis impotent ( Armstrong, 1997 ; Furman, 2000 ). Furman (2000) concluded,
· I have tried to trace the thinking that followed the discovery of the vastly different approaches in the United States and Europe to the management of the active or overactive child.… This thinking led to the conclusion that ADHD is not a specific disorder or pathological entity but rather a collection of symptoms that could be manifested by a child in distress, a child in conflict within himself and/or with his environment. It has no more specificity than that, and likewise methylphenidate has no specificity in producing its effects.… Suppressing these symptoms by “subduing” the child with medication hides from all the source of the child's troubles, precludes his being able to obtain mastery of his troubles through understanding, and subjects him to a false label of brain pathology. (p. 141)
Furman, now deceased, indicated that his conclusions were not new but simply ignored.
AN OVERVIEW OF PEDIATRIC AND ADOLESCENT PSYCHOPHARMACOLOGY
By the time this text has been published, only a handful of psychotropic medications will have been approved as on label for the preschool age group. Examples include methylphenidate/Ritalin, amphetamine/Adderall, haloperidol/Haldol, and chlorpromazine/Thorazine ( Zito et al., 2003 ). Methylphenidate/Ritalin is now under great scrutiny ( Zaicek, 2009 ). For preschool-age children, it is aggressive behavior that generally triggers a referral for treatment ( Bassarath, 2003 ). A few more psychotropic medications have been approved for use in older children and adolescents ( Kluger, 2003 ), but those (such as the antidepressant fluoxetine) are hotly debated because of suicidal risk. Table 9.2 lists as many medications as we were able to find with on-label approval for children.
We have mentioned the national dilemma that more children and adolescents demand psychological services each year, yet there are fewer service providers. Concurrent with this expanding problem is the dramatic increase in the use of psychotropic medications off label for a variety of mental and emotional conditions and disorders. Although this is problematic in and of itself, the focus on psychological and interpersonal factors in treating children and adolescents has dangerously diminished. Whereas it used to be common practice for child psychiatrists to choose in each case from among drug therapy—primary drug therapy and secondary counseling, or primary counseling and secondary drug therapy ( Kraft, 1968 )—today these choices are rarely discussed routinely.
Also note that DSM criteria are primarily normed on adults and are more difficult to apply with children. House (1999) has indicated that over half of the time, children who meet the criteria for one mental or emotional disorder meet criteria for other disorders as well. This multiple nature of children's problems frequently results in a polypharmacy approach and requires careful decisions by the physician and/or treating team ( Brown & Sammons, 2002 ). How carefully those decisions are made varies from setting to setting and clinician to clinician and are more random today (Leslie, 2011).
Researchers do know that the preschool years are one of the key developmental periods for maturation of the brain dopamine system, which is targeted by stimulants ( Coyle, 2000 ). The FDA-approved package insert on methylphenidate/Ritalin warns against its use with children under age 6. Given all the unknowns, many scholars and physicians are concerned about the quality and care and the current explosion of prescribing practices with preschoolers. Mental health professionals do not have enough clear evidence about how preschoolers respond to psychotropic medications, and researchers are very uncertain about the impact of such medications on the development of preschoolers. Let's examine some of the major developmental issues.
TABLE 9.2 Drugs with FDA On-Label Approved Uses in Children
Developmental Issues
For many of you, this section on human growth and development in children and adolescents is a review. Most texts on development emphasize cognitive, language, moral, and psychosocial developmental paths. We briefly consider these lines of development
and include others that are potentially affected by the ingestion of psychotropic medication. Understanding development is further complicated by the construct of developmental lines —the simultaneous occurrence of several aspects of human growth and development.
Developmental Lines
Although there are dozens of lines of human development, this multiplicity is still not a focus for mental health professionals outside of developmental studies. What should be common knowledge for mental health professionals is still peripheral to their training. For example, the Council for the Accreditation of Counseling and Related Educational Programs (CACREP) requires only one human development course for a master's degree in school or clinical mental health counseling. There may be dozens of lines of human development. These include physical development, cognitive development, emotional development, sexual development, moral development, spiritual development, kinesthetic development, socioemotional development, gender identity, and role-taking ability. These are just a few of the lines of development to which every person has access, and, for the most part, everyone proceeds through them unevenly.
The sheer number of developmental lines and the fact that most people proceed unevenly through them raise enormous, unaddressed issues for psychopharmacology. We noted earlier that scientists know very little about how brains develop and that many researchers are concerned that psychotropic medications could profoundly damage the brains of children and adolescents when taken long term. Glen Elliott, director of the Langley Porter Psychiatric Institute Children's Center of the University of California at San Francisco, noted that the current use of psychotropic medications on children “has outstripped our knowledge base . . . we are experimenting on these kids without tracking the results” ( Kluger, 2003 , p. 51). For example, even when an adolescent truly appears to suffer from Bipolar I Disorder, the sequelae of mood stabilizer side effects such as weight gain and perhaps hair loss are likely to be more devastating for a person of that age than for an adult—but there is no research on such psychological issues.
Perhaps the greatest problem of studying child and adolescent psychopharmacology from the four integrative perspectives is that whenever the issue of medicating children comes up, the only perspective represented is that of the medical model. A good example is a Time magazine cover story, by Kluger (2003) that basically explores only the medical model perspective, with only minor attention to psychological, cultural, and social issues. The same article presents a diagram showing what parts of the brain are believed to be correlated with different mental or emotional disorders. At no point in the article does the author state that these areas are hypothesized to be correlated with symptoms and there is no evidence that they cause symptoms. This remains true as of the second edition of this book.
As we have noted throughout the book, many symptoms that are psychogenic in origin register in the brain, but this does not mean the symptoms were caused by the brain. This bias toward the medical model perspective leads laypeople to assume that mental/emotional disorders, whether in children or adults, are strictly medical disorders. This assumption is not currently supported by the evidence we have been covering in this book. A full-scale multimodal approach to mental and emotional disorders in children and adolescents considers medication and possible brain pathology as only one part of the story in a very complex interaction of tentative causes and interventions.
Developmental Pharmacology
Developmental psychopharmacology is a newer area of research that studies brain development focused on brain plasticity (the brain's ability to shape itself to environmental or chemical input) and sensitive periods (during which experience can alter neural representation before hardwiring occurs) ( Carrey, Mendella, MacMaster, & Kutcher, 2002 ). Pediatric psychopharmacology is an equally young enterprise with the first published reports dated in 1937 but by the 1980s the United States
had become the world leader in medicating children ( Riddle, Walkup, & Vitiello, 2008 ).
Although these disciplines are examining development strictly from the medical model perspective, its overarching question is, “What happens in the complex process of neural development when an infusion of psychotropic medications is introduced to address particular environmental stressors during periods of accelerated brain development?” Compared to adults, children and adolescents respond to psychotropic medications in different and distinctive ways that have implications for efficacy and safety ( Vitiello & Jensen, 1995 ). The rate at which prescriptions of psychotropic medications have grown for children despite the dearth of research to support their efficacy raises the question “are we doing too much or too little?”
Epstein (2001) posited that active brain growth spurts occur stagewise in correlation with Piagetian types of development. Thus, a child who is making the transition from the sensory motor stage to Piaget's preoperational stage is in a very active brain growth stage (from age 2 to 4 years). Epstein cites Boothroyd (1997) , who noted that lexical knowledge and syntactic knowledge grow rapidly until age 4. At about 6 (from age 6 to 8), the next rapid brain growth period parallels Piaget's concrete reasoning stage, where a child begins to think logically about experienced inputs, the concrete operational stage. Epstein discussed the next brain growth period as slow (from age 12 to 14 years), a time of practicing and consolidating new networks in preparation for the next rapid brain growth stage (between ages 14 and 16 years). Psychotropics often are administered to preschoolers in the rapid growth period between ages 2 and 4 years, and to early-latency children between the ages of 6 and 8 years. Mental health professionals do not know enough about the impact of both on-label and off-label psychotropics in these rapid brain growth periods to be administering them to children and adolescents. Bramble (2003) concluded that given the changing nature of pediatric pharmacology and developmental pharmacology, this society needs a rapid expansion of pediatric research and academic inquiry into the impact of psychotropics on children's development. The second author in an extensive review of developmental pharmacology articles found only those supported fully by pharmaceutical companies or ones that cost between $29.50 and $40.00. Almost all recommended the use of a psychotropic as a first-line intervention. Interestingly, the pharmaceutical companies signed documents stating that they had no “conflict of interest.” In addition, the medications being used are only partially successful 40–50% of the time ( Rapoport, 2013 ).
Another problem with pediatric psychopharmacology is polypharmacy : the use of more than one psychotropic simultaneously, a usage that interacts with children's metabolism in a variety of unpredictable ways ( Brown & Sammons, 2002 ). Clinicians who observe children and adolescents under the influence of polypharmacy are often startled not only by the dramatic change in the clients' affective and behavioral state but also by the array of side effects they experience. Tonya, a very aggressive 12-year-old, was placed on olanzapine/Zyprexa (an atypical antipsychotic), sertraline/Zoloft (an SSRI antidepressant), lorazepam/Ativan (an anxiolytic), and valproate/Divalproex (a mood stabilizer). This combination of medications was ostensibly for what appeared to the attending psychiatrist as Bipolar I with severe agitation and aggression in the manic phase. Tonya's symptoms diminished, but her teacher noticed new ones: slurred speech, mild tics, and a constant staring off without responding when addressed. Now, rather than disrupting the class, she slept through it. Although from the perspective of the teacher and other students this was an improvement, was Tonya being helped, or was she merely medicated into submission when she might have been more fundamentally helped with assessment and therapy from a wider interpersonal perspective?
Other developmental considerations include adverse cardiovascular effects. We have many reports of sudden deaths of children and adolescents treated with psychotropic medications, including methylphenidate/Ritalin, TCAs, SSRIs, bupropion/ Wellbutrin, lithium, and most neuroleptic medications. Gutgesell et al. (1999) detailed the
cardiovascular and electrophysiologic effects of commonly used psychotropic medication, which can be deadly. Although the precise causes of the deaths have not been documented, severe heart spasms (cardiac arrhythmias) and delayed repolarization of the heart rhythm (delayed QTc interval) make the heart muscle vulnerable to possibly lethal changes (such as ventricular tachycardia). These tragedies call on mental health professionals to be vigilant and cautious when prescribing psychotropic medication. With many high-risk medications, cardiovascular monitoring is particularly important. In fact, Wagner and Fershtman (1993) recommended ECG monitoring at baseline and during drug therapy for children and adolescents who are on the medications associated with cardiovascular side effects. Brown and Sammons (2002) argued that the use of most psychotropic medication exceeds data available for efficacy, effectiveness, and safety.
Many concerns also remain related to the physiological impact on children who take psychotropic medication. One is the controversy about the impact of stimulant treatment on brain growth in children ( Bell, Alexander, Schwartzman, & Yu, 1982 ). Researchers have recently learned that methylphenidate and other stimulants decrease blood flow to selected parts of the brain, specifically the cortex area that controls conscious movement ( Zeiner, 1995 ). In a recent study ( Castellanos et al., 2002 ), the research team concluded that developmental trajectories for all brain structures, except caudal, remain parallel for children and adolescents in ADHD patients and controls. This suggested that genetic and early environmental influences on brain development in ADHD are fixed, nonprogressive, and unrelated to stimulant treatment.
However, initial brain scans of patients with ADHD showed significantly smaller brain volumes in all regions than what appeared in the brain scans of the controls. In general, because of brain plasticity (the brain's ability to shape itself), it is possible for children to be highly susceptible to a negative impact on their brain development during one period of development and less so in another period of development ( Carrey et al., 2002 ). Does treatment with psychotropic medications constitute a negative impact? These authors further concluded that researchers are only beginning to understand the long-term effect of psychotropic medication on neuron cell factors and their overall impact on brain development. All these developmental concerns or issues involve potential adverse effects for children and adolescents taking psychotropic medication.
At this point, we cover the different categories of medications used on children and adolescents. We begin the next section with a more thorough treatment of stimulant medications.
Review Questions
· • What are some of the main problems with the increase in psychotropic medication prescriptions for children?
· • What was the impact of the FDA Modernization Act and the Best Pharmaceuticals Act for Children? Name at least three changes these acts initiated.
· • What are the “developmental unknowns” that make prescribing psychotropic medications for children problematic?
SECTION TWO: STIMULANT MEDICATION
Learning Objectives
· • Understand the mechanism of action and side effects of stimulant medications.
· • Be able to discuss the type of symptoms stimulants seem most helpful for.
Even though stimulants are currently the beststudied psychotropic medication used on children, many issues regarding their use are still unresolved. Because stimulants are prescribed almost exclusively for children, we have included information on them in this chapter. Before discussing some of
the controversial issues, let's examine some background and general information on these widely prescribed medications.
Some History
The first known stimulant in the West was cocaine. It was isolated in 1859 by a German chemist named Albert Niemann and was given to Bavarian soldiers to decrease fatigue. In 1884 Karl Koller perfected its use as an analgesic during eye surgery. His assistant, a young neurologist named Sigmund Freud, was off visiting his fiancé at the time and so missed out on credit for that discovery. Freud had been personally experimenting with cocaine and wrote the paper “Uber Coca” (“On Cocaine”) prior to realizing its addictive qualities ( Freud & Carter, 2011 ). Many people in South American societies still regularly chew coca leaves with little ill effect, because unprocessed leaves are far less dependence inducing than is refined cocaine powder ( Siegel, 1989 ). Efforts to synthesize amphetamine began in 1887, when physicians believed it useful for treating asthma. This belief emerged from the use of an herbaceutical called ma huang in Chinese medicine. Ma huang is discussed more thoroughly in Chapter Ten on herbaceuticals, but for now understand that it is the ingredient ephedra that is central to the story of amphetamines. This ingredient produces the bronchial dilation that relieves the wheezing of asthma.
In the 1920s, a Chinese pharmacologist working for Eli Lilly (K. K. Chen) was working to isolate and synthesize ephedra from ma huang. He succeeded in synthesizing a compound so structurally similar to ephedra that it was named ephedrine. Although this could be taken orally, the goal for asthma treatment was a compound that could be inhaled. Gordon Alles succeeded in developing another variation of the molecule that could be delivered in an inhaler. Called Benzedrine, this variation was successful in treating asthma. Aside from treating asthma, it also seemed to induce euphoria. People soon realized they could open the inhaler and ingest the contents for what became known as “the amphetamine rush.” This also became a popular pastime on college campuses during exams. Amphetamines were experimented with to manage a number of disorders, and one of their early uses was treating children for what was described as “overactivity.”
Werry has asserted that research in psychopharmacology for children began with publication of Bradley's (1937) paper on how amphetamine seems to calm overactive children and help children with learning disabilities. The only other noteworthy investigations of the same period were studies on the effects of antihistamines on children ( Connors, 1972 ). These works are thought to be the only primary contributions to child psychopharmacology until very recently ( Werry, 1999 ).
Bradley's work reemerged in the 1960s after psychiatry began moving away from a psychodynamic model toward the biological model dominant today. Psychiatrists at that time were not well trained in the statistical methods that were becoming the norm in evaluating medications. They turned to psychologists for assistance. The psychologists emphasized the need to look at medication effects on learning and academic performance ( Werry, 1999 ). Such research has, until very recently, remained focused primarily on stimulant medication.
Research in pediatric psychopharmacology received an unintentional boost in the 1960s with the creation of a diagnosis called Minimal Brain Dysfunction (MBD). MBD was one of the several precursors to the current ADHD diagnosis. MBD was treated with stimulant medications such as methylphenidate. Although later discarded because it was too vague, the MBD diagnosis did much to lead to the development of a norm for a methodology with which to evaluate the effects of drugs, and particularly stimulants, on children.
In WorldWar II, German, British, American, and Japanese soldiers all used amphetamines, a practice still common in the U.S. Air Force to help pilots keep alert on bombing missions ( Knickerbocker, 2002 ). After World War II, the Japanese had such huge surpluses of amphetamines that they marketed them to civilians. These drugs were advertised for the elimination of drowsiness and repletion of spirit. Researchers estimate that by 1948, 5% of the Japanese population between the ages of 15 and 25 was dependent on amphetamines.
After World War II, it became evident that amphetamines have appetite suppressant qualities, and chemists tried to tease these out from the reinforcing properties that were connected to abuse. However, most of these initial efforts (such as methylphenidate/Ritalin) failed, and then the drugs were simply marketed as amphetamines.
The amphetamine molecule is a simple and highly malleable molecule that acts as the chemical template for over 50 pharmacologically active substances ( Grilly, 1994 ). Amphetamine is basically made of two compounds (isomers) labeled “L” and “D” amphetamine. D-Amphetamine is more potent and was marketed as Dexedrine. A minor modification in this molecule yields methamphetamine marketed as Methedrine. Other variations of the amphetamine molecule can produce MAO inhibitors. Modifying amphetamine to dimethoxy-methylamphetamine (DOM) produces a psychedelic compound similar to mescaline, and further modification produces the empathogen methylene-dioxymethamphetamine (MDMA, street name “ecstasy”). The latter was a promising psychotherapeutic compound until criminalized ( Eisner, 1994 ). The therapeutic effects revolved around chemically induced states of empathy, euphoria, and well-being that facilitated insights that were then to be integrated into clients' normal awareness ( Stevens, 2009 ).
Table 9.3 outlines stimulant medications used to treat ADHD in children.
TABLE 9.3 Stimulant Drugs Used to Treat ADHD in Children
© Cengage Learning®
Mechanisms of Action in Amphetamines
Amphetamines exert almost all their effects by causing the release of norepinephrine and dopamine from the synaptic vesicles into the synaptic cleft. There are different mechanisms for amphetamines to act as dopamine agonists and the number of mechanisms used depends on the type of amphetamine. There are two isomers of amphetamine, “L” and “D.” The “L” isomer amphetamine mechanisms of action include:
· • Pure reuptake inhibitor for DA
· • No presynaptic activity
· • Enhances NMDA receptor response
· • Weak block monoamineoxidase
· • 80% metabolized
· • The classic L-isomer amphetamine is methylphenidate/ Ritalin
The D-isomer amphetamine mechanisms of action are similar to those of cocaine and include:
· • Reuptake inhibition of DA (inhibit DAT)
· • Drug taken into terminal by DAT & depletes vesicles (causes DA transporter to act in reverse) thus releasing DA from the presynaptic neuron
· • Enhances NMDA receptor response
· • Weak block of monoamineoxidase (MAO)
· • Releasing NE from presynaptic neuron
Amphetamine/Dexedrine is the classic D-isomer amphetamine but is less prescribed than Adderall. Mixed amphetamine salts/Adderall includes D-amphetamine.
In a study comparing methylphenidate to cocaine, Volkow et al. (1995) noted that although the mechanisms of action and effects are similar, methylphenidate clears more slowly from the brain, which, they hypothesize, makes it less dependence inducing. Readers are encouraged to think critically about this result, because when a similar mechanism of slow clearance is invoked to defend cannabis (marijuana) as low in dependenceinducing qualities, it is often rejected ( De Fonseca, Carrera, Navarro, Koob, & Weiss, 1997 ). Either the mechanisms discussed decrease the probability of dependence or they do not. Pharmaceutical and political agendas should be separated from this debate so that people can objectively examine the issues. In previous chapters, we have listed the adverse effects of psychotropics being discussed. With ADHD, these effects are interwoven into the complex presentation of the stimulants. We ask you to consider why in the continent of Europe (an area of the world that has about the same population as the United States), stimulant medications are used with children for only about 5 to 8% of the treatment population so treated in the United States. Now let us examine the DSM-5.
ADHD Diagnosis and Assessment
According to the DSM-5, the diagnostic criteria for attention-deficit/hyperactivity disorder are
· A. Either (1) or (2):
· (1) six or more of the following symptoms of inattention have persisted for at least five months to a degree that is maladaptive and inconsistent with developmental level: Inattention
· (a) often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities
· (b) often has difficulty sustaining attention in tasks or play activities
· (c) often does not seem to listen when spoken to directly
· (d) often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions)
· (e) often has difficulty organizing tasks and activities
· (f) often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework)
· (g) often loses things necessary for tasks or activities (e.g., toys, school assignments, pencils, books, or tools)
· (h) is often easily distracted by extraneous stimuli
· (i) is often forgetful in daily activities
· (2) Hyperactivity: Six (or more) of the following symptoms of hyperactivity impulsivity persisted for at least six months to a degree that is maladaptive and inconsistent with developmental level: Hyperactivity
· (a) often fidgets with hands or feet or squirms in seat
· (b) often leaves seat in classroom or in other situations in which remaining seated is expected
· (c) often runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness)
· (d) often has difficulty playing or engaging in leisure activities quietly
· (e) is often “on the go” or often acts as if “driven by a motor”
· (f) often talks excessively
· Impulsivity
· (g) often blurts out answers before questions have been completed
· (h) often has difficulty awaiting turn
· (i) often interrupts or intrudes on others (e.g., butts into conversations or games)
· B. Several hyperactive-impulsive or inattentive symptoms that caused impairment are present before age 12 years.
· C. Several inattentive or hyperactive-impulsive symptoms are present in two or more settings.
· D. There must be clear evidence of clinically significant impairment in social, or occupational functioning.
· E. The symptoms do not occur exclusively during the course of a Pervasive Developmental Disorder, Schizophrenia, or other Psychotic Disorder and are not better accounted for by another mental disorder (e.g., Mood Disorder, Anxiety Disorder, Dissociative Disorder, or a Personality Disorder). ( APA, 2013 , pp. 59–60)
Source: Diagnostic and statistical manual of mental disorders, 5th ed., (Washington, DC: American Psychiatric Association, 2013 ).
Both the “Consensus Statement” of the National Institutes of Health (1998) and the “Clinical Practice Guidelines” of the American Academy of Pediatrics (AAP) (2011) recommend careful diagnosis of ADHD and then an appropriate and judicious use of stimulants in combination with other psychosocial treatments to address the symptoms. Epstein et al. (2010) also emphasize that children treated with stimulant medication show improvement in ratings by parents and teachers but not in their level of functioning as measured by grades. Thus they note that mental health services in addition to medication are important.
In terms of assessment most protocols recommend a neurologic exam, a consultation with a psychiatrist or psychologist who specializes in ADHD, behavioral observation reports from parents, grandparents, teachers, and other school personnel. Olfson, Gameroff, Marcus, and Jensen (2003) , analyzing national data, reported the increased rates of treatment from 0.9 per 100 children in 1987 to 3.4 per 100 children in 1997. They posited that this increase along with fewer treatments (counseling) per child was attributed to a broader awareness of the diagnosis by special educators, growth of managed behavioral health care, and increased public acceptance of psychotropic medications. But we ask, has the mushrooming of the ADHD diagnosis in children led to improved assessment and treatment?
The answer is mixed. Although some teachers, school administrators, and pediatricians rapidly diagnose ADHD in children, the NIH (1998) , the National Institute of Mental Health (NIMH) (1996 , 2000 ), and the AAP (2001) all have developed diagnostic guidelines for ADHD for years. More recently, The American Academy of Child & Adolescent Psychiatry (AACAP) (2007) released a practical, evidence-based practice parameter. In 2011 the same group released a practice guideline with expanded treatment of how to make the diagnosis and how to add psychosocial interventions to treatment ( AACAP, 2011 ). The initial guideline was again updated in 2012. In all cases, these expert societies recommend a careful evaluation by a trained psychiatrist or psychologist in conjunction with teachers, mental health professionals, and family members. They recommend an evaluation period that is not rushed, so the team can rule out other conditions that might be confused with ADHD, and which includes observation and rating scales.
In a 10-year review of rating scales assessing ADHD, Collett, Ohan, and Myers (2003) concluded that DSM IV-based rating scales can reliably, validly, and efficiently measure ADHD symptoms in youth. In this comprehensive review, the authors evaluated the validity and sensitivity of subscales on several rating scales to assess the symptoms of ADHD. The greater use of narrowband rating scales in the assessment of ADHD can supplement and complement clinical interviews and behavioral observations in the evaluation of ADHD in children and adolescents. It is now evident that reliable and valid ADHD rating scales can augment the accuracy and specificity of diagnosis.
In a comprehensive response to the Multimodal Treatment Study ( Owens et al., 2003 ), the authors sought to answer the layered question, “What do we treat in ADHD?” and “Who treats it?” based on the needs of the child and her or his circumstances ( Paul, 1967 , p. 111). Their findings were remarkable. The children least likely to respond well to a combined treatment of stimulants and milieu therapy were those with depressed parents or caregivers and severe ADHD. Owens et al. (2003) examined several outcome predictors, using nine baseline child and family characteristics. None were
predictive, but the two issues discussed earlier along with a lower IQ of the identified child correlated with an outcome less-than-favorable with the combined treatment.
ADHD Efficacy, Effectiveness, and Conundrum
ADHD has been classified as one of the externalization disorders, along with Conduct Disorder and Oppositional Defiant Disorder. As opposed to the other two, stimulant medication has been the treatment of choice for ADHD for about 25 years in the United States ( Phelps et al., 2002 ). In fact, stimulants for ADHD are the most widely researched and used medications in child psychiatry. Evidence indicates significant increase in the use of stimulants for both preschoolers and children despite the fact that the FDA approval is only for children ages 6 and older ( Brown & Sammons, 2002 ; Riddle et al., 2001 ; Zito et al., 2000 , 2003 ). The data include empirical evidence on safety, efficacy, and adverse effects.
Research demonstrates the beneficial effects of stimulants on symptoms linked with ADHD. These effects include diminished inattention, impulsivity, overactivity ( Bennett, Brown, Carver, & Anderson, 1999 ), improved classroom attention and academic efficiency ( DuPaul & Rappaport, 1993 ), and improved mother–child relationships ( Barkley, Karlsson, Strzelecki, & Murphy, 1984 ). However, with all the benefits cited for the use of stimulants with ADHD, available literature to date has not supported or demonstrated that stimulants enhance school achievement ( Phelps et al., 2002 ). Short-term efficacy studies supported the impact of stimulants on the target symptoms. From this literature, clinicians can conclude that using stimulants with children appropriately diagnosed with ADHD diminish the child's inattention, impulsivity, and hyperactivity, but do not necessarily improve his or her academic achievement. It is very possible that the child will adapt better to the demands of the classroom environment and become less externally driven. However, it would also be interesting to research whether or not stimulants improve performance in children who are not diagnosed with ADHD.
Proponents of stimulant treatment for ADHD are more convinced than ever that the disorder is passed on through heredity via the DRD4 receptor gene and that, as twin studies have suggested, up to 80% of the variance in the trait of hyperactivity/ impulsivity is now considered to be based on genetics ( Barkley, 1998 ). Peter Jaska (1998) , president of the Attention Deficit Disorder Association (ADDA), is a staunch advocate of stimulant treatment for ADHD and argues that “we cannot and will not turn back decades of scientific research on the biological basis of ADHD, medical research, educational progress, and federal disability legislation, because some people selling books claim that ADHD is a ‘myth' ” (p. 1). Both Jaska and Barkley are experts on the biological bases for ADHD derived from the medical model perspective and the resulting medication for treatment, but they seldom address intrapsychic, cultural, or social perspectives of ADHD.
Review Questions
· • What are the mechanisms of action and side effects of stimulant medications?
· • What types of symptoms are stimulants most useful for?
SECTION THREE: ADHD AND COMBINED INTERVENTIONS
Learning Objectives
· • Understand the differences between the initial, twoyear, and eight-year follow up of the MTA study group.
· • Be able to describe conditions that may be comorbid with ADHD and why this may also be a misdiagnosis.
Interventions with ADHD usually begin with assessing the child or adolescent for oral stimulant medication, because most studies have indicated short-term behavioral improvement related to the symptoms of
the disorder when stimulants are used ( American Academy of Pediatrics, 2001 ; Barkley, DuPaul, & Connor, 1999 ; Phelps et al., 2002 ). Methylphenidate/ Ritalin accounts for 90% of the prescriptions for ADHD ( Advokat, Comaty, & Julien, 2014 ). In the late 1990s studies demonstrated that Adderall (amphetamine/dextroamphetamine) is equally efficacious but methylphenidate/Ritalin is still the leader in medications used to treat ADHD.
As noted, most consensus statements on ADHD treatment recommend psychosocial interventions that assist the family as well as the person diagnosed with ADHD. These approaches include psychotherapy, cognitive-behavioral therapy, behavioral therapy, social skills training, impulse control therapy, parenting skills training, support groups, and family therapy. Each of these approaches alone or in conjunction with stimulant medication can help ameliorate some of the symptoms of ADHD and/or address some of the underlying factors affecting the person with the disorder. The American Academy of Pediatrics (2001) first treatment guideline specifically recommended behavioral therapy as the best adjunct intervention with stimulants to establish targeted outcomes and manage the child's behavior both in the classroom and at home. They also stated that if one stimulant does not work at the highest feasible dose, the physician should recommend another. Clinicians learning about pharmacology may find it helpful to remember that stimulants generally provide only relief of symptoms, thus requiring other treatment modalities and followup. In a follow-up to that Bader and Adesman (2010) recommended a list of complementary and alternative treatments for ADHD. Although the American Academy of Pediatrics did not recommend these specifically they did note that essential fatty acid supplementation is well tolerated and modestly effective.
Results of the Multimodal Treatment Study for Children with ADHD ( MTA Cooperative Group, 1999 ) demonstrated initially that stimulant treatment was slightly more effective than behavioral therapy alone, and equally effective to therapy and medication combined. It should be noted that parents preferred the behavioral therapy conditions to the stimulants-alone treatment. As with all treatment approaches for ADHD, the MTA study is not without its critics, who argue for a better match of patient with a treatment strategy tailored and selected for the individual's needs ( Green & Albon, 2001 ). When the selected management (interventions) for a child with ADHD has not met targeted outcomes, clinicians must evaluate the original diagnosis, adjust treatments and medications, and evaluate for coexisting conditions.
Another critic of the MTA study ( Leo, 2002 ) noted that the fanfare surrounding publication of the study “was nothing short of extraordinary” (p. 53). Leo pointed out that ABC News reported that results indicated drug therapy was much better than counseling for ADHD. Leo contends that the MTA study was heavily biased toward medication treatment. He claims the study's authors all had a history of strongly favoring medication, bringing their objectivity into question. He also points out that the MTA study had four groups: one received medication, one received behavior therapy, one received both, and a fourth group received no treatments from the MTA researchers but instead received standard treatment in the community. The most “robust” changes were reported in ratings by teachers and parents of children in the study. The problem with this, according to Leo, is that the investigators preselected a group of parents who believe it is acceptable to medicate children; in fact, in all cases the parents contacted the investigators to enroll children in the study. This fact, according to Leo, points to a bias in the sample.
Edwards (2002) addressed the important follow-up outcomes of studies and interventions in the wake of the report from the MTA Cooperative Group study (1999) . He recommended that a specific family-based intervention be used in a mental health setting in conjunction with pharmacologic treatment. He specifically cited Parent Management Training (PMT) as an approach that through cognitive-behavioral coaching helps parents manage their child's difficulties. Whatever the method, more physicians, researchers, and clinicians are recommending family interventions with children and adolescents diagnosed with
ADHD. The research in treatment outcomes of ADHD is complicated, and we encourage you to evaluate many strategies and interventions for your clinical work, especially those that include family/ parent strategies.
The MTA study was followed up at two years and at eight years. Here is a summary of the findings. At two years, cessation of drug treatment was correlated with significant clinical decline. Continued drug therapy was correlated with moderate decline and initiation of stimulant therapy for those in control group was correlated with significant improvement ( MTA Cooperative Group, 2004 ). So at this point again the cornerstone of treatment seemed to be with the medication. At the eight-year follow up, 33% of the subjects were still on medication (and 83% of them were on stimulants). Improvement was maintained but the group had not “normalized” meaning there were still significant achievement gaps between them and so-called “normal” controls. Thirty percent still met the DSM-IV criteria for ADHD (though one suspects more would meet criteria under DSM-5 because you only need five criteria met rather than six). Overall, medicated children did better in math and reading. There was still a significant test score gap between children in the study and the control group. Also, interestingly, approximately 30% showed signs of antisocial behavior and 25% showed signs of Oppositional Defiant Disorder ( Barnard-Brak & Brak, 2011 ; Sheffler et al., 2009). This is interesting because many specialists felt that the antisocial behavior often comorbid with ADHD was because the ADHD was untreated. It seems that there may be something else to the antisocial behavior because it seemed to persist in so many people despite their longterm treatment for ADHD.
We spoke with one interventionist who provides a learning/coaching service to children with ADHD ( Joyce Kubik, Personal Communication, April 2003 ). Kubik not only conducts specific skill-building training/coaching for ADHD children but also conducts support groups for parents. She also gives workshops for teacher in-service programs. Her overall message is that children with ADHD are capable of developing specific learning strategies that will lead to improved academic learning and success. She outlines these specific skills in her book S.C.O.P.E.: Student Centered Outcome Plan and Evaluation ( Kubik, 2002 ). The central theme of her work is to help parents and teachers find ways to help students with attention difficulties. The American Academy of Child & Adolescent Psychiatry (2001) stated,
· Research also should include the role of school and community-based professionals, as well as primary care clinicians, in delivering treatment services. Little is known about how short or long-term effectiveness varies as a function of the school and community-based professional involvement…. They should consider child and family outcomes and cost-effectiveness of care. Linking outcomes to service parameters is an important step in encouraging practice in system change. (p. 10)
In this summary statement, you can recognize aspects of the multimodal model that forms the basis of this book in analyzing and evaluating interventions with children and adolescents diagnosed with ADHD. It calls for more comprehensive research on the multiple factors that contribute to ADHD in children and adolescents and initiates the process to improve research on outcomes with this disorder.
ADHD and Comorbidity
The American Academy of Pediatrics (2001) also stressed that evaluation for ADHD should include an assessment for coexisting or comorbid conditions. The literature on ADHD identifies several psychological and developmental disorders that coexist in children with ADHD ( Biederman, Mick, Faraone, & Burback, 2001 ; Phelps et al., 2002 ; Spencer, Biederman, & Wilens, 2002 ). These disorders included conduct and oppositional defiant disorders, mood disorders, anxiety and depressive disorders, mental retardation, learning disabilities, tics, substance abuse, and medical conditions. Researchers have estimated that among children with ADHD, the prevalence rate of
Oppositional Defiant Disorder is up to 35%, Conduct Disorder up to 26%, anxiety disorders up to almost 26%, and depression up to 18% ( AAP, 2001 ). It is more difficult to estimate comorbidity rates of Bipolar Disorder, substance abuse, and tics. Most authors who discuss comorbidity and ADHD tend to discuss the issue from a pharmacologic perspective rather than a counseling perspective ( Levy & Hay, 2001 ; Solanto, Arnsten, & Castellanos, 2001 ). This is a burgeoning and complex conundrum in the treatment of ADHD. We encourage you to be alert to the great variability in children and adolescents diagnosed with ADHD and to assess for other conditions or factors.
Susan L. Andersen (2005) studied stimulants and the developing brain. She found that the effects of stimulant drugs during different stages have unique short-term, acute effects that also influence their long-term effects. Chronic, pre-pubertal exposure alters the expected developmental trajectory of brain structure and function and results in a different topography in adulthood. She also discovered that the timing of exposure (childhood vs. adolescence), the age of examination after drug exposure (immediately or delayed into adulthood), and sex influenced observable effects. Hopefully this can provide new treatment options for ADHD.
Mental health clinicians should be able to recognize the evidence recommending cautious use of stimulants with children and adolescents diagnosed with ADHD, and should remain alert to the potential for overdiagnosis or misdiagnosis of the disorder and the extensive range of comorbid/coexisting conditions. Phelps et al. (2002) summarized issues surrounding comorbidity of ADHD, ODD, and CD related to the evidence that when two or more of these disorders occur together, the prognosis is more guarded. They also addressed the hypothesis that ADHD occurs first in the child and the symptoms of impulsivity and inattention interact with the psychosocial issues of family turmoil, parental problems, and abuse factors to trigger ODD and/or CD. Clinicians need to be alert to the range of symptoms of several disorders when assessing and evaluating symptoms of impulsiveness and hyperactivity. These conditions could emanate from psychological family and environmental factors. Although the debate continues about the effectiveness of stimulant medication with ADHD, Greenhill (1998) and NIH (1998) concluded that stimulants used for ADHD children and adolescents
· 1. Producemoderate tomarked short-termimprovement in motor restlessness, on-task behavior, compliance, and academic performance.
· 2. In studies of six months or longer, children fail to maintain academic improvement or improve social problem-solving skills ( Greenhill, 1998 , p. 53).
Atomoxetine, a Nonstimulant
Recently, atomoxetine/Strattera, a nonstimulant and a selective norepinephrine reuptake inhibitor (SNRI) has demonstrated some promising results in reducing ADHD symptoms ( Brown University, 2002 ). It was approved for use in children ages 6 and older in 2003 and for maintenance treatment of ADHD in children and adolescents in 2008. Atomoxetine/Strattera is metabolized primarily through the CYP2D6 enzymatic pathways. It demonstrates an adverse event percentage of between 3.5 and 7% (poor metabolizers) in clinical trials. These adverse events include gastrointestinal problems, irritability, insomnia, aggression, and dizziness. As a nonpsychostimulant, atomoxetine/ Straterra has potential as an alternative to the stimulants now used with ADHD. As with any new medication, only time and continued research will tell if atomoxetine will improve on the side effect profile of stimulant medications.
In a very sad and disappointing statement, the status of the treatment of ADHD has not changed in seven years since the first edition of this text.
· • Children, adolescents, and adults are being diagnosed at accelerated rates.
· • The first and second course of treatment is pharmaceuticals.
· • Efforts by the FDA, legislation like the Best Pharmaceuticals for Children Act have been marginalized.
· • Limited assistance for the poor, Medicaid, wards of the county or state, orphans and other children,
· and adolescents with restricted access to quality medical care.
· • A belief still that life is better through pharma— just watch TV since the Health Care Act passed in 2009.
· • Society's intolerance for anxious, agitated, and aggressive children.
· • Large metropolitan school systems' inability to understand the impact of bullying on students with disabilities.
So with little progress, more children take the drugs and some experience improvement whereas many others graduate to more potent pharmaceuticals.
Review Questions
· • What were the differences between the initial findings of the MTA study and the two-year and eight-year follow up?
· • What does the eight-year follow-up tell us about antisocial behavior and ADHD treatment?
· • What conditions may be comorbid with ADHD and why may these be a case of misdiagnosis?
SECTION FOUR: MOOD STABILIZERS AND BIPOLAR I DISORDER IN CHILDREN
Learning Objectives
· • Be able to think critically about the problems of putting children and adolescents on medications tested on adults.
· • Be able to articulate alternatives to so-called mood stabilizing medications for children.
The DSM-5 ( American Psychiatric Association, 2013 ) provides the following diagnostic criteria for Bipolar Disorder, Single Manic Episode:
· A. Presence of only one Manic Episode and no past Major Depressive Episodes. Note: Recurrence is defined as either a change in polarity from depression or an interval of at least two months without manic symptoms.
· B. The Manic Episode is not better accounted for by Schizoaffective Disorder and is not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.
Criteria for Manic Episode
· A. A distinct period of abnormality and persistently elevated, expansive, or irritable mood, lasting at least one week (or any duration if hospitalization is necessary).
· B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
· (1) inflated self-esteem or grandiosity
· (2) decreased need for sleep (e.g., feels rested after only three hours of sleep)
· (3) more talkative than usual or pressure to keep talking
· (4) flight of ideas or subjective experience that thoughts are racing
· (5) distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)
· (6) increase in goal-directed activity (either socially, at work, or school, or sexually) or psychomotor agitation
· (7) excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).
· C. The symptoms do not meet criteria for a Mixed Episode.
· D. The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.
· E. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).
Source: Diagnostic and statistical manual of mental disorders (5th ed., Text Revision, pp. 123–125). Washington, DC: American Psychiatric Association, 2013.
We have seen in the past decade an increasing interest and shift in focus from Conduct Disorder (CD) and Oppositional Defiant Disorder (ODD) to Bipolar I Disorder in children and adolescents ( Kusumaker, Lazier, MacMaster, & Santor, 2002 ; Milkowitz et al., 2014 ). We illustrated this in the case of Phillip at the beginning of this chapter. Although in our Chapter Eight discussion of mood stabilizers we focused on Bipolar I Disorder, in this chapter we use the more general BPI, because that is the construct common to the literature on children and adolescents. Many diagnostic scholars tell us the prevalence of BPI is growing, especially in preadolescent children, with almost no gender differences ( Bland, 1997 ; Hirschfeld et al., 2003 ; Zarate & Tohen, 1996 ). The case for increased incidence is still undecided.
In the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM-5; American Psychiatric Association [APA], 2013 ), BPI is the basis of a new category, Bipolar and Related Disorders. BPI is the centerpiece of this section, which also includes Bipolar II Disorder, Cyclothymic Disorder, Bipolar Disorders related to substance use or medical conditions, and other specified and unspecified Bipolar and Related Disorders. In order to stem the tide of BPI misdiagnoses in children, Disruptive Mood Dysregulation Disorder was introduced to the DSM-5 section on Depressive Disorders. The jury is still out on whether this will reduce the false diagnosis of BPI in children ( Margulies, Weintraub, Basile, Grover, & Carlson, 2012 ) or, for that matter, how we should treat Disruptive Mood Dysregulation ( Jairam, Prabhuswamy, & Dullur, 2012 ).
There is considerable controversy regarding the appropriateness of a BPI diagnosis in children. Questions regarding the appropriateness of such a diagnosis are founded on the idea that criteria for BPI may overlap with criteria for developmental issues; other disorders usually diagnosed during infancy, childhood, or adolescence (e.g., what the DSM-5 calls Neurodevelopmental Disorders); and other problems known to affect people of all ages (e.g., depressive, anxiety, substance use, and impulse-control disorders) ( Chang, 2008 ). Further, there are currently no pediatric diagnostic guidelines for BPI in children, and it is inappropriate to use the DSM criteria for BPI because they were normed on adults ( Kowatch et al., 2005 ; Sahling, 2009 ).
One of the most problematic issues is assuming that any type of irritability or acting out is somehow related to the invalid notion of a “bipolar spectrum.” Differentiating between irritability (very common in children and adolescents) and symptoms of BPI is an ethical imperative for clinicians, particularly those working in foster care or with other children and adolescents who have no one to advocate for them ( Banaschewski, 2009 ; Sahling, 2009 ). Although published studies using functional brain-scanning technologies to investigate early-onset BPI are few, some show brain anomalies similar to those that correlate with adult BPI ( Frazier et al., 2005 ). Only longitudinal studies will answer the question regarding how predictive such anomalies are for the development of BPI because brain scans can only suggest endophenotypes that are related to vulnerability to a disorder ( Jackson, 2006 ).
The problems with the exponential increase in diagnosing pediatric bipolar disorder are many. In many children, rapid mood swings can be normal. The treatment guidelines ( Kowatch et al., 2005 ) admit that “no one can say for sure what these children will look like when they grow up” (p. 214). This is a disturbing statement because BPI, properly diagnosed, is thought to be a chronic disorder. The authors of the treatment guidelines admit that the DSM symptoms for adult mania are problematic when used for children, but then they recommend continuing to use them. Overall, the treatment guidelines fail to draw distinctions between normal children and those really afflicted with BPI ( Sahling, 2009 ).
Currently, the DSM-5 diagnostic criteria for Bipolar Disorder are used for children and adolescents without any major modifications and the features providing the best distinction between ODD,
CD, ADHD, and BPI are the presence of a flight of ideas, grandiosity, and the episodic nature of the grandiosity ( Carlson, 1996 ; Kusumaker et al., 2002 ). As we summarize the literature on BPI in children and adolescents, we learn that it is difficult to diagnose, more clinicians are recognizing its prevalence at an earlier age of onset, three tentative developmental theories are linked to it ( McMahon & DePaulo, 1996 ), and more clinicians are using antimanic medications to treat BPI in both children and adolescents.
Soutullo et al. (2005) concluded that there is an overdiagnosis of Bipolar Disorder in the United States when compared to several countries like Spain, Turkey, India, Brazil, Switzerland, Denmark, and Finland. This difference may be attributed to a relative lack of data, differences in diagnostic criteria, different levels of recognition of child and adolescent psychiatry as a true specialty in Europe, clinician bias against Bipolar Disorder, an overdiagnosis in the United States, and/or a true higher prevalence of BD in the United States. It sounds like the same case with ADHD.
Viesselman (1999) addressed the general symptoms of BPI as expansive mood, inflated selfesteem, decreased need to sleep, talkativeness, flight of ideas, distractibility, psychomotor agitation, and excessive involvement with pleasurable activities. Phelps et al. (2002) addressed the fact that BPI youth often are incorrectly diagnosed as having Schizophrenia; thus, BPIs are difficult to discern in children and adolescents because many present with an agitated depressed mood rather than mania ( Weller, Weller, & Fristad, 1995 ). Lewinsohn, Klein, and Seeley (1995) stated that pediatric clients with BPI present with more psychomotor agitation, elevated mood, increased verbalizations, inflated self-esteem, distractibility, and a decreased need for sleep. Duffy (2010) detailed with great specificity the potential genetic markers for children who might be vulnerable to inherit Bipolar I.
The treatment of choice for BPI in children and adolescents is the mood stabilizers covered in Chapter Eight . These drugs include lithium/Eskalith, Lithobid, valproate/Depakote/Depakene/Divalproex), carbamazepine/Tegretol, oxcarbazepine/Trileptal, and olanzapine/Zyprexa. Many scholars already cited in this chapter argue against indiscriminate use of these medications with pediatric populations without further study and argue for more complete awareness of the dynamics affecting the child.
Riddle et al. (2001) discussed the finding that the older antiepileptic drugs had been well researched as mood stabilizers in adults but not in pediatric populations. Campbell, Kafantaris, and Cueva (1995) have studied lithium/Eskalith, carbamazepine/ Tegretol, and valproate/Divalproex used for children with nonspecific aggression and found lithium/Eskalith was superior to placebo and to the other antiepileptic drugs in reducing aggression. One very important note: Eberle (1998) found that one type of adverse event of using valproate with girls is that of polycystic ovarian disease, which can have profound consequences for females.
In the early 21st century, children and teens are 40 times more likely to be diagnosed with Bipolar Disorder than they were in the late 20th century ( Miller & Barnett, 2008 ). As noted above there is evidence that this is due to diagnostic inflation and not an epidemic-level increase in the disorder. Geller et al. (2012) compared lithium/Eskalith, valproic acid/Divalproex, and risperidone/Risperdal in a trial called Treatment of Early Age Mania (TEAM). The response rate for risperidone/Risperdal was significantly higher (68%) than for lithium/ Eskalith (36%) or valproic acid/Divalproex (24%). Advokat et al. (2014) note that quetiapine/Seroquel and aripiprazole/Abilify are as effective as risperidone/ Risperdal. As noted in the chapter on antipsychotics though, these drugs come with severe side effects like weight gain and disruption of metabolic functions that can lead to type 2 diabetes.
In our clinical work of over 40 years, we have found that the comorbid substance use disorders were a major missing piece in several cases with children and adolescents. These clients were diagnosed with ODD, CD, or BPI and seemingly did not improve with psychotherapy or psychotropic interventions. The missing link and confounding variable was their hidden polysubstance abuse or
dependence, which exacerbated some symptoms and masked others. The links in the literature show how the onsets of BPD, ADHD, CD, or ODD become significant risk factors in diagnosing substance use disorders. It should be noted that any attempts to procure research papers on pediatric or child papers on the research topics of developmental pharmacology, ADHD, BP I, and pharmaceuticals related to these disorders published in 2013 or 2014 were sponsored by pharmaceutical companies and cost $39.00.
The following case may provide additional understanding of these complex variables.
THE CASE OF NICOLE
Nicole, a 14-year-old Caucasian girl currently living in a foster home, had just been referred to a Severe Emotional Disturbance (SED) unit in her school system. Nicole had a history of acting out, impulsivity, distractibility, conduct, and learning problems from a very early age. Initially, Nicole was referred to a specialist for her impulsivity and distractibility both at home and in preschool at the age of 4.
During the assessment, the clinician suspected a mood disorder but seemed to have more evidence for ADHD. He recommended a daily course of amphetamine salts/Adderall with behavior management therapy at home and school, focused on specific age-appropriate behaviors. At the time of the evaluation, he did not notice Nicole's intermittent scratching of her genital area. Over the next six months, Nicole showed little improvement in her symptoms and behaviors as a result of the amphetamine salts/Adderall and the milieu behavioral therapy. In fact, some of her behaviors worsened: she attacked other children, was cruel to animals, and was overtly curious about male and female genitals. After nine months, the psychologist consultant at the school recommended another neuropsychiatric evaluation and an outside therapist who would address some of Nicole's apparent psychological conflicts along with her behavior.
The second psychiatric evaluation yielded a change in diagnostic perspective. This time, the psychiatrist diagnosed BPI and prescribed valproic acid/Divalproex and a low dose of lorazepam/ Ativan, an anxiolytic. The new therapist, a female, stopped the behavior therapy and began to treat Nicole with a combination of play therapy and insight-oriented therapy. The play produced associations to remote possibilities of earlier sexual abuse and abandonment, and the insight therapy captured her already highly critical superego (obsessive thought patterns and preoccupation with sexual act) and her deep affection for the rituals of the Catholic Church. Nicole remained on this treatment regimen for about two-and-a-half years. During treatment, she never really settled down in class or at home, but her behavior and attention were slightly more manageable. (We have all had cases where there is just enough improvement from the medication to raise expectations even if the client seems not to be making progress in many important areas of her life.) Later, Nicole developed a passion for reading 7 to 10 books a week that she got from the local library. On her trips back and forth to the library, she befriended some older boys (ages 10 to 13) who offered her street stimulants at a very low cost. Nicole welcomed the friendship and experimented with the drugs (stimulants, soapers, cocaine), but was gangraped by the boys one Saturday afternoon. Overwhelmed by this horrific sexual trauma, Nicole did not speak of it to anyone. She also immediately stopped associating with the boys. Her response to this event was alternately to withdraw into a cocoonlike isolation and to become aggressive with people.
She verbally assaulted teachers and foster parents and attacked her friends and other students. She was unreachable and totally out of control. She stopped attending her therapy sessions with the counselor, but she continued to seek street drugs.
Puzzled and frustrated, the school crisis team recommended an additional psychiatric evaluation and assessment for Nicole and possible hospitalization. This triggered a series of episodes in which she ran away, had several foster and specialized school placements, a brief stay at a juvenile detention facility, one abortion, and two attempts at drug rehabilitation for her dependence on stimulants, cocaine,
and now alcohol. Somehow Nicole survived and is now in an SED classroom with a specialized social worker as an aide. She is on olanzapine/Zyprexa for psychotic mania, sertraline/Zoloft for depression and anxiety, low doses of valproic acid/Divalproex for violent and aggressive outbursts, and zolpidem/ Ambien as needed for sleep. In essence, at 14, Nicole was loaded with psychotropic medications (polypharmacy). She was referred to a new female therapist, with whom she rarely spoke; when she did, she mentioned missing her former, caring play therapist, one of the most stable objects (people) in her life. Although Nicole did attend her class regularly and her behavior was quite manageable, her teachers reported very little learning progress and a total inability to interact with her classmates. Her therapist echoed much of the same descriptions, but voiced marginal hope when she and Nicole engaged in drawing or other forms of play therapy or discussed issues related to an all-loving versus all-punishing God. The concluding remarks in her individual educational plan (IEP) at school read, “No change, few academic gains, impulsive/ aggressive behavior stabilized, little socialization, continues in counseling.”
Examining this case from our four perspectives yields some important insights and omissions. Nicole did receive a more extensive assessment early on and participated in behavioral therapy first, which is recommended by the literature ( AAP, 2001 ; Kusumaker et al., 2002 ; Phelps et al., 2002 ) followed by art therapy and insight therapy when the behavioral therapy failed. It is critical to note that the second therapist helped Nicole discuss psychological and cultural issues and learned about the pressure from her complicated feelings about her upbringing in the Catholic Church and her deep awareness of her selfcritical feelings and thoughts.
As is so often the situation with a foster child, other social and cultural pressures intervened, such as drug abuse, negative and exploitive peer relationships, and sexual trauma. It is not clear whether Nicole ever experienced sexual or physical abuse earlier in her life. The most recent team is faced with an early adolescent girl with a long history of psychotropic and psychotherapeutic treatments whose life is further complicated and traumatized by rape and drug dependence. Given the assumption that the significant others in her life—case managers, foster parents, teachers— feel she is out of control, the attending psychiatrist then addressed her range of symptoms and conflicts with a polypharmaceutical strategy. This approach numbs and tranquilizes Nicole so she is more appropriate in her various living environments but fails to address the boiling issues, anguish, and conflicts from the other aspects of her life. Treatment for Nicole should begin by recognizing the extreme complexity of her life space and developing a treatment plan and approach to gradually help her titrate off some of her medications while addressing in counseling the complex issues of abuse, drug dependence, abandonment, and loss of self that so plague her. She will need a very extended and interpersonal treatment approach if she is to recapture hope and resiliency in her life. We also would speculate about the accuracy of her diagnosis, because of the interplay of her conflicts and varying presenting problems and lack of empathy in her counseling.
Review Questions
· • What are some of the problems of putting children and adolescents on medications tested on adults?
· • What alternatives do we have to so-called mood stabilizing medications for children?
SECTION FIVE: CHILDREN AND ANTIPSYCHOTIC MEDICATION
Learning Objectives
· • Know the diagnoses for which typical and atypical antipsychotics are being used in children.
· • Be able to discuss the problems with this practice.
Schizophrenia with adolescent onset has been noted since the earliest descriptions of the disorder. Readers will recall Emil Kraepelin's initial diagnosis of a
patient as having “dementia praecox,” which means “youthful insanity.” As Russell (2001) notes, given that the disorder has been linked with adolescents through the evolution of its diagnostic forms, one might think there would be ample treatment literature regarding these populations, but there is not. Childhood-onset schizophrenia (prior to age 12) is even rarer than adolescent onset. It is estimated that maybe 1 child in 10,000 would suffer this before the age of 12 ( Remschmidt, 2002 ). The differential diagnosis must include substance-use disorders, depressive disorders with psychotic symptoms, and what DSM-5 calls other neurodevelopmental disorders like Autism Spectrum Disorder ( Androutsos, 2012 ). Even when criteria are met it is very difficult to diagnose schizophrenia in a child. The Child Psychiatry Branch at the National Institute of Mental Health (NIMH) conducted a longitudinal study of childhood onset schizophrenia. Outpatient screening accurately diagnosed 55% of the 121 cases. However, inpatient observation including medication-free observation ruled out 96 children with alternative diagnoses. Outpatient screening only accurately diagnosed 62% of this same group. The conclusion the researchers drew was that inpatient, unmedicated observation was the most accurate way to diagnose these children ( Gochman, Miller, & Rapoport, 2011 ).
In a review of controlled studies of antipsychotic agents to treat Schizophrenia, Campbell, Rapoport, and Simpson (1999) found only one controlled study of the use of these agents with adolescents and one report on their use with children younger than age 12. Therefore, Russell (2001) notes, until more research is conducted clinicians must extrapolate from adult studies to children and adolescents, which poses many risks. Although he comments this is not cause to adopt a nihilistic attitude, it does call for clinical skepticism. Russell maintains it may be true that people with early-onset Schizophrenia have more severe forms of the disorder, but this has yet to be determined conclusively and it does not mean pharmacologic treatment will not be effective. Further, early-onset Schizophrenia seems to have more severe negative symptoms, making the atypical antipsychotics a better choice if the children can tolerate the adverse drug effects ( Botteron & Geller, 1999 ).
Although few data are available regarding the use of antipsychotics with childhood psychoses, in the 20th century the neuroleptic haloperidol/ Haldol was used because it tended to be less sedating ( Andreasen, 2000 ). Because of the potential for Parkinsonian-like symptoms, this medication was often prescribed with an anti-Parkinsonian agent such as benztropine/Cogentin. Ernst et al. (1999) ; Phelps et al. (2002) ; and Riddle et al. (2001) also addressed the use of the “atypical” newer neuroleptics for children diagnosed with tics, behavioral problems in autism, psychotic illness, and nonspecific aggression. In 2004, Toren et al. ( Toren, Ratner, Laor, & Weizman, 2004 ) did a benefit-risk assessment of atypical antipsychotics in treating schizophrenia and comorbid disorders in children. They found the atypicals seemed to work better than neuroleptics and now it seems that neuroleptics like haloperidol/ Haldol are only used if the patient does not respond to an atypical. Of the atypical, risperidone/ Risperdal and olanzapine/Zyprexa seemed to improve cognitive functions and inhibit suicidal behavior. Madaan, Dvir, and Wilson (2008) noted that the FDA concluded there was enough support for using atypicals in children and approved two atypicals for childhood schizophrenia.
As we noted in Chapter Seven , evidence is mounting that atypical antipsychotics are also correlated with increased risk for diabetes and hyperglycemia and that this risk includes children and adolescents ( Koller, Cross, & Schneider, 2004 ). Research by Correll et al. (2009) confirmed these mounting suspicions. The study concluded that use of aripiprozole, olanzapine, quetiapine, and risperidone for 12 weeks all produced weight gain, and varied in lipid and metabolic parameters. The authors called for more careful monitoring of the child's health before using an atypical. Whatever medication a clinician chooses, Russell (2001) emphasizes the need for multimodal treatment that includes psychosocial interventions such as individual and family therapy, psychoeducational counseling, and social skills training.
A more common problem is raised by Pappadopulos et al. (2002) in a study that examines the range of off-label prescribing of atypical antipsychotics for aggression. These authors state that although in theory doctors seem to agree about optimal prescribing practices, in the “real world” there is wild disparity in the prescriptions written. Apparently, even the agreement between researchers and front-line doctors can be influenced by staff pressure, limited staff resources, managed care limits on inpatient stays, and the movement away from physical restraint.
Another problem that requires further debate and research concerns the notion that Schizophrenia is a wide spectrum of early-onset disorders manifesting in a variety of the disorder called “schizotaxia,” which refers to a genetic predisposition to Schizophrenia ( Meehl, 1962 ). Tsuang, Stone, and Faraone (2001) advocate treating Schizophrenia prophylactically. These authors maintain that the theoretically genetic predisposition toward Schizophrenia may be associated with reversible problems and may improve the child's quality of life. Despite this strong medical model perspective, they admit that psychosocial interventions may also work. They conducted a six-week trial of risperidone (prescribed at low levels) in six subjects identified as schizotaxic. They reported that five of the six reported increased cognitive abilities during the trial as well as greater enjoyment of social activities. Obviously, there is no way to determine the amount of placebo effect until a double-blind, placebo-controlled trial is done.
Great caution needs to be exercised here, as the implications are that asymptomatic children might be given antipsychotics in the hope that their diagnosis as schizotaxic is correct. The antipsychotic market currently amasses $5 billion a year, and many fear that the theory of schizotaxia is just another way of bending the parameters of diagnosis to help pharmaceutical companies profit from a new market. Currently, no diagnostic system in the world identifies adolescents in the phase before onset as ill, so this approach would have ramifications for the diagnosis. Ideally, the issues surrounding the politics of research and publishing described in Chapter Two , need to be more adequately addressed before any further medicating of asymptomatic populations. As Frances (2013) noted, preventive psychiatry could only work if we know the etiology of a disorder and have a safe and effective treatment for the disorder. We have neither where schizophrenia is concerned.
In Chapter Seven , we discussed neuroleptics and their affinities for different CNS receptors, their pharmacokinetics, and pharmacodynamics. Marriage (2002) spoke to our inability to predict the response of an individual patient (child or adolescent) to a typical or atypical neuroleptic. He addressed the enormous response variation, especially with adolescent males, Asians, Native Americans, and people suffering fromvarious forms of organicity. For children or adolescents exhibiting symptoms of psychosis, the longterm prognosis is poor ( Phelps et al., 2002 ), and we need to learn a great deal more about the adverse side effects of both the typical and atypical medications ( Riddle et al., 2001 ). Given the outcome of Olfson et al. (2006) National Trends Study, which indicated that children treated with second-generation medication (atypical antipsychotics) included descriptive behavior disorders (37.8%), mood disorders (31.8%), pervasive developmental disorders or mental retardation (17.3%), and psychotic disorders (14.2%), we are again reluctant to endorse atypicals as a treatment of choice for childhood psychosis.
Review Questions
· • What are some of the conditions for which children are being put on antipsychotic medications?
· • What are the main drawbacks to this practice?
SECTION SIX: ANTIANXIETY MEDICATIONS AND CHILDREN AND ADOLESCENTS
Learning Objective
· • Understand particularly how anxiolytic medications are used with children who have school anxiety.
Despite the high prevalence of anxiety disorders in children (10 to 20%), very few controlled medication trials have been conducted. In DSM-5, Obsessive-Compulsive Disorder (OCD) and Post Traumatic Stress Disorder (PTSD) have been given their own categories. Children's anxiety disorders, Separation Anxiety Disorder, Selective Mutism, Specific Phobia and Generalized Anxiety. In the late 20th century, Brown and Sawyer (1998) concluded that regarding anxiolytic medication with children, “few published empirical studies support their long term efficacy for children and adolescents” (p. 83). Bernstein and Shaw (1997) noted that psychotropic medications should not be the sole intervention but should be used as an adjunct to counseling. Interventions that facilitate active mastery are important, to prevent symptoms returning after discontinuation of medication. Little has changed and almost 20 years later anxiety disorders in children are first best treated with nonpharmacological therapies like behavior therapy, cognitive-behavior therapy, and internalizing prevention programs. House (1999) noted that children's disorders can be generally grouped as externalizing (like acting out against others) and internalizing. Internalizing often results in anxiety symptoms. Young children with anxiety disorders are more likely to be depressed and to exhibit temperamental inhibition and sleep problems ( Doughert et al., 2013 ).
The 2013 article of Rapp et al. will guide our complex study of anxiety disorders. The DSM-5 and earlier versions have really not assisted our journey to discover effective treatments for children and adolescents suffering from anxiety disorders (AD). It is the second author's opinion that there have been too many changes in the DSM related to AD since 1980. Our focus needs to shift to treatment with safe and effective outcomes. Bernstein, Borschardt, and Perwien (1996) viewed these changes as placing at risk a decade of research on childhood anxiety disorders, although Phelps et al. (2002) supported elimination of some categories of childhood anxiety disorders from DSM III-R as a research-based simplification of the categories. Although prevalence rates vary for current anxiety disorders with children and adolescents ( Botteron & Geller, 1999 ; Garland, 2002 ), incidences of Generalized Anxiety Disorders (GAD), and Separation Anxiety Disorder (SAD) are frequently thought to require both psychopharmacologic and psychotherapeutic interventions. Currently, although almost all the drugs are used off label, SSRIs such as paroxetine/ Paxil, fluvoxamine/Luvox, fluoxetine/Prozac, citalopram/ Celexa, and sertraline/Zoloft are prescribed for children and adolescents with anxiety disorders. Advokat et al. (2014) noted that fluoxetine/Prozac may be the best medication if medication is necessary. The current concern over safety of these medications for children and adolescents applies to their use in anxiety disorders as well as in depression. One of chronic side effect of SSRIs recognized in children is a behavioral activation ( Riddle et al., 1991 ), like an increased agitation different from a mania. As noted earlier the Food and Drug Administration (2003) issued a Public Health Advisory stating that use of SSRIs and similar types of antidepressants with depressed children and adolescents may be linked to increased suicide rates. How this will affect use of these antidepressants for anxiety disorders remains unclear. Rapp, Dodds, Walkup, and Rynn (2013) continued to use SSRIs in their combined treatment approaches with children diagnosed with GAD, SP, and SAD. Their study gave very high marks to Cognitive-Behavioral Therapy (CBT) in conjunction with a psychopharmacological approach.
In a review of the literature on anxiolytic medications used in pediatric populations, Livingston (1995) noted mixed results with benzodiazepines and said that in cases where studies show initial results, the results fail to be significant in replications of the studies. Livingston notes that if children are going to be placed on these medications, prescribers need to “start low and go slow” (p. 248). Recall from Chapter Six , benzodiazepines such as alprazolam/ Xanax and diazepam/Valium have an inhibitory impact on the CNS at the GABA receptor complex. As Advokat et al. (2014) note these drugs usually cause cognitive impairments and so are not recommended except in the case of shortterm medical procedures (e.g., dental procedures).
SCHOOL ISSUES, ANXIETY, AND CHILDREN
A relevant law when addressing anxiety in children is the Individuals with Disabilities Education Act (IDEA). Services to children are provided under a number of provisions in this act, and often many DSM anxiety disorders can be used to qualify a child for services. The diagnostic categories of DSM do not automatically correspond to the eligibility categories in IDEA. The interested reader can go to http://www.ed.gov/offices/OSERS/IDEA/the_law.html for a listing of the relevant diagnoses. IDEA services focus on disability conditions that interfere with a child achieving academically or vocationally.
Anxiety disorders have been used to qualify a child for special services. A key symptom is fears associated with personal or school problems that persist over a period of time and adversely affect educational performance. Anxiety disorders are one of the most common childhood disorders and may impair a child's life even if symptoms are below the threshold for a DSM diagnosis. For example, some studies show “subclinical” anxiety to be highly correlated with reading difficulty ( Bernstein & Shaw, 1997 ). Currently, studies are underway to measure the impact of bullying on anxiety ( Twemlow, Fonagy, Sacco, & Brethour, 2006 ).
Developmental differences exist in the presentation of the anxiety disorders. For example, younger children with Separation Anxiety Disorder have far more symptoms than older children. In adolescents, somatic complaints and school refusal are more common than in younger children. Conversely, older children with GAD show more symptoms than younger ones. This is probably caused by cognitive differences, because older children have more mental tools with which to craft their worries.
Interestingly, in several studies with benzodiazepines, the medicated groups did no better than placebo controls. Two studies did yield significant differences among school refusers and children with selective mutism and social phobia. In one study, the school refusers did better than controls when given Tofranil/imipramine, a tricyclic antidepressant. The other study, on selective mutism and social phobia, showed that the experimental subjects did better than controls when given Prozac.
A related childhood disorder is Separation Anxiety Disorder. Here, the anxiety is aroused by separation from familiar people (usually parents) or leaving home. The reaction is excessive and may include fears that something will happen to the parents or to prevent reunification. Somatic complaints are also common. The distinction must be made between developmentally normal separation anxiety and this disorder. If refusal to go to school is thought to be due to Separation Anxiety Disorder, the child will go if accompanied by the parent. Although benzodiazepines and antihistamines have been used to treat this ( Wozniak et al., 1997 ), exposure-based interventions and relaxation are likely to be more effective.
Another subthreshold condition is shyness. It is consistently correlated with adult and childhood anxiety disorders. Although common (90% of people report feeling it at some time in their lives), it can be debilitating as the person gets older. Shy men marry later and become parents later than their counterparts who are not shy. Although shy women marry and become parents at ages comparable to their counterparts who are not shy, they are less likely to attend college or work outside the home. Social phobia is a severe manifestation of shyness that afflicts about 5% of children. It delays social and emotional development. The overwhelming fear of doing or saying something embarrassing or humiliating keeps such people from eating, drinking, or writing in public or engaging in everyday conversations.
Although children generally outgrow shyness, they do not outgrow Social Phobia. Children with social phobias are usually depressed and lonely and almost always solitary. They may show extreme anxiety in situations where they feel they are being evaluated by others. The onset of Social Phobia is usually in adolescence and without treatment, the course is often chronic. There is high comorbidity with depression, other anxiety disorders, and substance abuse to self-medicate. As with other
childhood anxiety disorders, the recommended treatments include rehearsal, imagery, and drug treatment with antidepressant compounds. Behavior therapy has a 70% success rate for both children and adults, with systematic desensitization and exposure being the common treatments. Although more children and adolescents are being prescribed SSRIs and SNRIs for shyness and Social Phobia, there is literature supporting the practice. Rapp et al. (2013) continued to use SSRIs as the pharmacological treatment of choice in their protocols with some success and marginal adverse effects in the pediatric population. They reported on one study that used pregabalin (Lyrica) with promising results with a pediatric population. There are too many adverse effects to pregabalin.
Review Question
· • How could anxiolytics be helpful to children with school anxiety?
SECTION SEVEN: ANTIDEPRESSANTS AND CHILDREN AND ADOLESCENTS
Learning Objectives
· • Understand why the black-box warning on antidepressants for children is important.
· • Be able to suggest the type of monitoring necessary if a child is on an antidepressant.
· • Know the “placebo problem” especially in reference to children and antidepressants.
Many reports have appeared on an increased incidence of MDD in children and adolescents. Although more studies on this have begun, there is always error in the epidemiologic methods used to gather such data, so such reports are far from conclusive ( Ingersoll & Burns, 2001 ). As McClure, Kubiszyn, and Kaslow (2002b) noted, many approaches are used for diagnosing and treating mood disorders in children, only a few have any empirical support. It does seem that when identified, childhood or adolescent depression is characterized by high rates of comorbidity with conduct, anxiety and attention deficit disorders, impaired social and vocational functioning, increased rates of substance abuse, eating disorders, and higher risk for completed suicide ( West, 1997 ). Given that, it is important to consider all treatments that may be helpful when a child or adolescent does manifest symptoms of depression.
Depression (unipolar) can be very difficult to discover, discern, and diagnose in children and adolescents. In children, the symptoms manifest themselves as hyperactivity, impulsivity, and aggressiveness. Grief and loss may trigger enuresis, sleeplessness, nightmares, and extreme stubbornness, depending on the age of the child ( Brown & Sammons, 2002 ; Riddle et al., 2001 ; Ryan, 2002 ; Viesselman, 1999 ). In fact, Ryan (2002) noted that depressive illnesses in children and adolescents can be protracted, recurrent, and continue into adulthood.
Newer research into the complexities of antidepressant action can help neurologists and clinicians better understand developmentally important age differences in the nervous system. Researchers are beginning to see that developing animals differ from older ones in serotonin-mediated responses. Very-early-onset stress may compromise later adaptive capacity of some of these systems ( Goldman-Rakic & Brown, 1982 ). Juvenile depression may also differ substantially from adult depression regarding the role of noradrenergic mechanisms and thus in the responsiveness to compounds that target norepinephrine. Practitioners need to be alert to warnings such as those by Coyle (2000) , who noted there is “no empirical evidence to support psychotropic drug treatment in very young children and that such treatment could have deleterious effects on the developing brain” (p. 1060).
Tricyclic Antidepressants in Children
Overall, the results have not supported data found in adult studies regarding the efficacy of tricyclic antidepressants in treating juvenile depression
( Cohen, Gerardin, Mazet, Purper-Ouakil, & Flament, 2004 ; Rosenberg, Holttum, & Gershon, 1994 ). The weight of currently available evidence suggests that TCAs as a group are indistinguishable from placebo, except in side effects ( Kutcher et al., 1994 ; Puig-Antich et al., 1987 ). The highest response rate in a study is about 44%. In addition, a significant risk arises of serious cardiac problems in developing bodies. The same conclusions hold true for the TCA derivatives such as desipramine/Norpramin and nortriptyline/Trazodone. Both have been fairly well studied, and researchers have failed to show significant therapeutic differences from placebo but did show a high number of adverse side effects. In addition, both still carry the risk of cardiovascular complications.
Research has demonstrated that TCAs (and MAOIs) have not revealed greater efficacy than that for placebo, and their adverse side effect profile is extensive, including reports of sudden cardiac death ( Birmaher, 1998 ; Brown & Sammons, 2002 ; Kye et al., 1996 ; Riddle, Geller, & Ryan, 1993 ; Werry, 1999 ). There is little support if any for the routine use of TCAs as a first line of treatment in children and adolescents. Therefore, it is disturbing that millions of prescriptions for desipramine and related compounds have been written for young people under age 18 ( Goleman, 1993 ). Sommers-Flanagan and Sommers-Flanagan (1996) recommended that such prescriptions be reserved for special cases where other treatments have proven ineffective or intolerable and that a thorough physical (including cardiovascular exam) should be conducted before beginning the medication. TCAs should be used in children only under the following conditions:
· • Full informed consent of patient and parent
· • A history of lack of response to more appropriate treatments
· • Full disclosure of side effect profile
· • Disclosure of cardiotoxicity of these compounds
· • When trials of more effective, available pharmacotherapies (SSRIs) have failed
Also, TCAs should be used with extreme caution, because the noradrenergic system (on which TCAs operate) does not fully develop until early adulthood ( Goldman-Rakic & Brown, 1982 ). This evidence has not changed.
SSRIs in Children
As noted, the FDA (2003) has currently issued a Public Health Advisory cautioning about a possible link to the use of certain SSRI antidepressants in pediatric populations and increased suicide rates. The antidepressants in the advisory are listed in Table 9.4 .
As noted, the SSRIs currently are used with children and adolescents for anxiety and depression. Fluoxetine/Prozac has received FDA approval for use in pediatric populations, and fluvoxamine/ Luvox is approved for treating OCD in children ( Brown & Sammons, 2002 ). All other SSRIs are prescribed as off label to children with depression as of this writing. Children and adolescents encounter the same adverse effects as when the SSRIs are employed with anxiety disorders. These compounds are more effective in children but not as effective as in adult samples. Glaxo-SmithKline pled guilty to criminal charges for promoting paroxetine for use in the pediatric agerange for the treatment of depression ( Hensley, 2012 ).
TABLE 9.4 Antidepressants Listed in 2003 FDA Public Health Advisory
© Cengage Learning®
It is important to note that adolescent girls are particularly vulnerable to depression when entering puberty ( Phelps et al., 2002 ; Silberg et al., 1999 ). Clinicians should be sensitive to gender, family history of depression, impacting life events, loss, or death when assessing children for depression. Current trends and preliminary understandings of the research suggest that in addressing childhood depression, the clinician must consider both psychotherapy and medication ( Badal, 1988 , 2003 ). Ryan (2002) indicated that 30 to 40% of children do not have a sufficient response to the first SSRI treatment.
There is almost no literature on the effects of SSRIs on infants and preschoolers ( McClure, Kubiszyn, & Kaslow, 2002a ); however, evidence shows SSRI prescriptions are on the increase for this age group ( Zito et al., 2000 ). The majority of researchers looked at the effects of fluoxetine (Prozac) on older children and adolescents, which has shown mixed results ( Emslie et al., 1997 ). Some studies looking at the effects of paroxetine on children and adolescents are also promising ( Findling et al., 2000 ; Keller et al., 2001 ), but more doubleblind, placebo-controlled studies need to be done. Juveniles with a family history for manic or hypomanic symptoms are at higher risk for SSRIinduced manic or hypomanic episodes. If children or adolescents are treated with SSRI medications, treatment should be cautious and should observe the following conditions:
· • SSRIs are used in addition to supportive psychotherapy or counseling to deal with psychological issues.
· • SSRIs should be supported by education regarding the symptoms, the medication, and what relief the medication is to provide.
· • Effective treatment involves parents or caregivers as much as possible.
· • Effective treatment includes use of a depression scale (HAM-D or BDI-II) if the child is old enough to take one, to monitor symptoms.
· • The acute phase of treatment should take place over 8 to 12 weeks followed by maintenance of 4 to 6 months.
McClure et al. (2002a) conclude that when medication is warranted, the SSRIs are the medication of first choice. Jureidini et al. (2004) disagree, however. They recently reviewed and critiqued seven published randomized, controlled trials of newer antidepressants for depressed children. These researchers found that pharmaceutical companies paid for the trials, the benefits of the drugs were small, and the adverse effects were downplayed, and they concluded antidepressant drugs could not be confidently recommended as a firstline treatment option. This is only one metaanalysis, but it points to the need for validity in published data and full disclosure of biases resulting from funding sources or researchers. Karger (2013) concluded that SSRI and even SNRI treatments for pediatric populations were/are too risky and this is from an international perspective. He stated that the SSRIs were more effective with anxiety disorders. Studies have been more compromised in pediatric populations with depression. Also, Craighead, Miklowitz, and Craighead (2013) summarized the work of Dr. Du of Shanghai who indicated that his studies demonstrate that SSRIs are safer in adolescents than in children. Dr. Du encouraged universal efforts of prevention to address the 17–20% of children who are depressed in all of our cultures.
From an integrative perspective, it is important to review all literature as it comes in, as well as review the researchers and the funding sources to check for possible bias. At the time of this writing, a new government-funded study of SSRIs and children was completed but not officially released in a peer-reviewed journal. The study was the Treatment for Adolescent with Depression Study (TADS), sponsored by the National Institute of Mental Health (NIMH). When we called NIMH to get a copy of the study, we were told the study needed to be peer-reviewed and the results would not be released until that process was complete. Nevertheless, Time magazine ( Lemonick, 2004 ) and The New York Times ( Harris, 2004 ) reported
(without benefit of peer review) that the study supported the use of the medications with children. When we asked the NIMH representative how the popular press would have gotten the results to report before the peer review, she said she didn't know. Until a peer review of the study is concluded, the writers have no basis for these conclusions other than their own opinions of the study. Without including the results of peer review, readers are likely to come away with a “sound byte” interpretation of the results that may not be accurate. Readers can access the latest results of drug trials on the NIMH website http://www.nimh.nih.gov/studies/2mooddisordersdep.cfm . We did not try for the results in 2014.
THE PLACEBO PROBLEM
As we noted in Chapter Five , the placebo effects of compounds and the place and type of placebo in studies has yet to be explicated. According to Fisher and Fisher (1997) , “A probe of the available scientific reservoir of pertinent studies does not reveal any serious evidence that antidepressants do more for childhood depression than do placebos” (p. 308). An earlier overview of studies by Thurber, Ensign, Punnett, and Welter (1995) concluded that the more adequate the experimental methods in each study, the less likely to be found superior to placebo were the drugs tested. Although Fisher and Fisher (1997) noted that the evidence is still limited for the effectiveness of many counseling/psychotherapy approaches to depressed children and adolescents, this does not excuse the prescribing of compounds for which very little evidence of efficacy and effectiveness exists.
In concluding this section, we remind the reader that clinicians are using off-label psychotropic medication for several other disorders. In each case, the clinician must weigh the benefit versus the potential adverse effects of the drug on the child. We must also speak to the child about his or her reaction and feelings about the medication and request feedback from the parents or guardians about the child's progress or struggles with the psychotropic medications. We believe it is an enormous responsibility to counsel children and adolescents who are on psychotropic medication where little research has been conducted on the efficacy, effectiveness, and safety of the drugs.
In April 2003, the recommendations were published of the Research Forum approved by the American Academy of Child and Adolescent Psychiatry (AACAP) on strategies for psychopharmacological studies on preschool children ( Greenhill et al., 2003 ). The six workgroups of the Research Forum were (1) diagnosis/assessment, (2) research design, (3) ethics/institutional review board (IRB), (4) preschool protocol modifications, (5) FDA/regulatory industry, and (6) training/public issues. Finally, when our text was reviewed in 2005, most psychiatrists challenged us on our strident positions about pharmaceutical research, medicating children, split-treatment (working together—psychiatrist and mental health professional), and the general tone of our text. Now we wish to extend our empathy to all psychiatrists who work under tremendous pressure to cure the incurable and find the magic pill.
Review Questions
· • Why is the black-box warning on antidepressants for children important?
· • If a child is put on an antidepressant, what sort of monitoring is necessary for the child?
· • What is the placebo problem with regard to children and antidepressants?
CONCLUSION
We have sought to highlight the complexity, controversy, and conundrums of child and adolescent psychopharmacology. By now, you are alert to factors from all four perspectives that impinge on this issue, generate “word magic,” provide partial truths, or stimulate errors. In the colossal debate over ADHD, we discover not only errors but an inflexibility that may harm children rather than treat them. We recognize the power and influence of the pharmaceutical companies to market so many “off-label”
psychotropic medications to children and adolescents with such confidence or, more accurately, grandiosity. Central to this dilemma are the shortages of mental health professionals and psychiatrists who exclusively treat children and adolescents. This shortage, coupled with the growing confidence of the effectiveness of psychopharmacology with some diagnoses, permitted pharmaceutical companies to market “off-label” drugs for children and adolescents on a grand scale while clinicians observe the phenomenon, almost powerless. Even the passage of the Best Pharmaceuticals Act for Children 12 years ago is not enough to slow this trend.
SUMMARY
The use of psychotropic medications with children and adolescents is very complex. Clearly there is no simple answer to this dilemma. Because most of the medications are prescribed off label, it is important that mental health professionals learn all that they can in order to protect the health and well-being of their clients who are children and adolescents. The information provided here spans the four perspectives to challenge the reader to consider medical, psychological, cultural, and social paradigms. The discussion of stimulant medications serves as a template for practitioners as they consider psychotropic applications with other disorders. When children or adolescents are placed on a psychotropic, it is always recommended that they receive counseling or other supportive services. The federal government through recent legislation is emphasizing how important and critical this issue is. Finally, the question is asked, “Do we as a society use psychotropic medication as the ultimate modality of behavior and anger management?”
CHAPTER NINE Medicating Children
This chapter is divided into seven sections. Section One is an overview that discusses current trends in medicating children, problems the trends cause, and directions for the future. It also discusses developmental issues. Section Two focuses on stimulant medication and the diagnosis of attention deficit hyperactivity disorder (ADHD). Section Three focuses on research on combined interventions and particularly the Multimodal Treatment Study (MTA study) of Children with ADHD. Section Four focuses on children taking mood stabilizers. Section Five focuses on antipsychotics and children. Sections Six and Seven focus on anxiolytics and antidepressants in children, respectively.
SECTION ONE: PERSPECTIVES, DILEMMAS, AND FUTURE PARADIGMS
Learning Objectives
· • Understand the problematic increase in psychotropic medications for children despite a dearth of evidence of the effectiveness of these drugs.
· • Have a general understanding of the impact of the FDA Modernization Act and the Best Pharmaceuticals Act for Children.
· • Be able to state the “developmental unknowns” associated with giving kids psychotropic medications.
Thus far, we have explored the medical model and psychological, cultural, and social perspectives as they relate to psychopharmacology. In this chapter, we demonstrate that using psychotropic medications with children and adolescents raises particular problems and concerns from several perspectives. As discussed in Chapter Three , we frequently see explanations and justifications from the medical model perspective used to reduce childhood disorders to chemical and genetic problems, excluding crucial consideration of environmental traumas, developmental foreclosures, or life stressors.
We explore child and adolescent psychopharmacology primarily from the medical model perspective but complement this approach with information from the other perspectives (psychological, cultural, and social). We set the stage by exploring the current status of the treatment of children and adolescents with mental and emotional disorders. This chapter is structured differently from the others in this book. We begin by discussing the context from the social and cultural perspectives and the problems with prescribing psychotropic medications to children. Then we cover an introduction to stimulants used to treat symptoms of ADHD. Finally, we give the status of their current use since the last edition of the book if that is possible.
THE COMPLEX STATE OF THERAPY
Dr. Frank O'Dell, Professor Emeritus of Counseling in the College of Education and Human Services at Cleveland State University, has argued in all his lectures on counseling children and adolescents that the United States is an “anti-kid” society (Personal Communication, 2001). By that he means fewer
and fewer therapists and psychiatrists choose to treat or continue to work with children in counseling. To support his argument, O'Dell points out that resources for children, including the number of hospital beds in mental health wards for children, have been shrinking. He believes the rules of managed care companies, dwindling personnel resources, and increasing difficulty in working with parents or guardians and their struggling children all contribute to the current trend. This has been a problem for at least 45 years. The American Academy of Child & Adolescent Psychiatry (AACAP) (2001) summarized the following facts, which support O'Dell's assertion, indicating little has changed:
· • There is a dearth of child psychiatrists. Satcher (2001) stated further that many barriers remain that prevent children, teenagers, and their parents from seeking help from the small number of specially trained professionals who are available and that places a burden on pediatricians, family physicians, and other gatekeepers to identify children for referral and treatment decisions ( U.S. Department of Health and Human Services, 2001 ).
· • The AACAP's report projected that between 1995 and 2020, the need for child and adolescent psychiatrists will increase by 120%, whereas the need for general psychiatry is projected to increase at 22% for the adult population.
· • McCarty, Russo, and Rossman (2011) demonstrated that only 13% of youth with suicidal behaviors and ideation receive mental health services.
· • In November 2010, the Coalition for Juvenile Justice estimated that up to 75% of teenagers in the juvenile justice system nationwide have a diagnosable mental disorder, and these numbers continue.
· • One in 10 children suffers from mental illnesses severe enough to impair development. Fewer than 1 in 5 children get treatment for mental illness.
The U.S. Department of Health and Human Services (2001) concluded that burgeoning numbers of children are suffering needlessly because their emotional, behavioral, and developmental needs are not being met by the institutions and systems created to care for them. As the number of children and adolescents needing psychological treatment rises and the number of service providers falls, the primary treatment modality becomes psychotropic medications rather than therapy. Imagine if you were a parent of one of these children.
Debner (2001a) reported that in a one-year period, 350 children needing hospitalization were turned away from hospitals in the Boston area. This phenomenon is occurring in most major U.S. cities and is exacerbated by hospitals holding onto children who are ready to be discharged, because there is no suitable placement for them. In another article, Debner (2001b) noted that the chief pediatricians from the five major academic health centers in Massachusetts indicated there is a serious crisis in psychiatric services for youth in the state. The doctors said they and their staffs could not find appropriate therapy and other mental health services for mentally ill children. As a result, many such children deteriorate to the point of crisis. Thomas and Holzer (2006) reported that America suffers from a serious longterm shortage of child psychiatrists that is taking a toll on young people, their parents, and their doctors. It is further recognized that the demand for psychotropic drugs is intense in spite of dangerous side effects.
The Washington Post (2002) published an article about a woman who desperately needed a psychiatric evaluation for her teenage daughter and who left 36 phone messages for various psychiatrists. She received only four replies. All the replies were from practitioners who refused to take the case because they did not treat adolescents. The article further detailed how, more and more, in-network providers (clinicians) prefer not to take patients covered by managed care plans, because reimbursements are so low and restrictions so numerous. The article also highlighted the disparity and arguments between the treating professionals and spokespeople from managed care companies. It is more than fair to say that desperate parents and anguished children are caught in the political policy dilemma over the cost and reimbursement of mental health treatment for children and adolescents.
Since the first edition of this book, there has been a movement to train more primary care physicians in pediatric mental health services to try to address the shortage of pediatric mental health professionals. Aupont et al. (2013) describe a model called Targeted Child Psychiatric Services designed for primary care physicians as well as child psychiatrists. This was associated with improved access to the child psychiatric services that exist, helped identify optimal care settings for patients and helped pediatricians be more likely to accept a patient back after that patient had been under psychiatric care.
Another problematic topic is who dispenses medications in schools. Most states have a policy on this and many states have a Nurse Delegated Medication Administration program ( Ryan, Katsiyannis, Losinski, Reid, & Ellis, 2014 ). Most standardized curricula include trainings of approximately 30 hours with 8-hour updates every two years or so. These are by and large directed by professional nurses ( Spector & Doherty, 2007 ). Nationwide lists of states and their programs can be found at http://www.nasbe.org/healthy_schools/hs/bytopics.php?topicid=4110&catExpand=acdnbtm_catD and http://www.healthinschools.org/health-in-schools/health-services/schoolhealth-services/school-health-issues/medicationmanagement/state-policies-on-administration-of-medication-in-schools.aspx .
THE EXPLOSION OF PSYCHOTROPIC MEDICATION PRESCRIPTIONS FOR CHILDREN AND ADOLESCENTS
With diminishing psychological supports for children and adolescents, using psychotropic medications with them has become the treatment of choice, even though the majority of medications used with them lack FDA “on-label” approval for them ( Werry, 1999 ). Researchers currently estimate that between 7.5 and 14 million children in the United States experience significant mental health problems ( Riddle, Kastelic, & Frosch, 2001 ; Wozniak, Biederman, Spencer, & Wilens, 1997 ). These statistics vary a little from Satcher (2001) , cited earlier; clearly, millions of children in this country require mental health services. Children are increasingly prescribed psychotropic medications as part of their treatment; in many cases, the medications replace the therapy ( Jensen et al., 1999 ; Phelps, Brown, & Power, 2002 ). Given the explosion in the use of psychotropic medication with children, it is important also to note that this population has been excluded from clinical trials of these drugs. Hence, decisions about juvenile medication obviously rest more on extrapolation of adult data to children and adolescents than on direct research and evaluation of the safety and efficacy of psychotropic medication with children ( Riddle et al., 2001 ; Vitiello & Jensen, 1997 ).
Coyle (2000) indicated that 80% of all medications prescribed to children and adolescents in the United States have not been studied for the safety and benefit of these populations. As of 2011, The National Institutes of Health indicated that methylphenidate, lithium, all atypical antipsychotics, lorazepam, and amitriptyline were still on the highest priority list of needs in Pediatric Therapeutics of drugs to be studied in pediatric populations.
Even though there is a black box warning related to the risk of increased suicidality in children and adolescents prescribed SSRIs and SNRIs, the use of these psychotropic agents has increased with children and adolescents ( Markowitz & Cuellar, 2007 ). The trend in treating children and adolescents with off-label psychotropic medications, mostly in lieu of counseling and psychotherapy, has triggered concern both in the general public and the mental health community. Coyle (2000) , Furman (1993) , and Zito ( Zito et al., 2000 , 2003 ) argue that there is little or no evidence to support psychotropic drug use with very young children and conclude that such treatment could have harmful psychological, developmental, and physical effects. In a multinational study, American youths were three times more likely to be on an antidepressant medication than their peers in Denmark, Germany, and the Netherlands ( Zito et al., 2006 ). In 2010, the pharmaceutical companies research protocols were really challenged when uncovered pharmaceutical studies on many highly utilized
psychotropics were found to be no more efficacious than the placebo. In fact, the second author has personal communications with several psychiatrists in their fourth or fifth decade of practice who question the overall effectiveness of psychopharmacology with patients, especially children (Ramirez, Personal Communication, 2014).
In another multinational study, Zito et al. (2008) found that the annual prevalence of youth taking psychotropic medication was threefold greater in the United States than in the Netherlands and Germany. The atypical antipsychotics represented 5% of antipsychotic use in Germany but 66% in the United States. Interestingly, though, anxiolytics were twice as common in Dutch youth than as in U.S. or German youth.
With proper research, mental health professionals may be able to head off disasters such as aspirin precipitating Reye's syndrome or valproate leading to sudden death in infants ( Riddle et al., 2001 ). Given the lack of knowledge about the long-term and adverse effects of psychotropic medication on children, it is crucial that mental health clinicians be alert to the impact of these drugs on children and advocate for youth when the evidence that such drugs would be helpful is questionable ( Ingersoll, Bauer, & Burns, 2004 ). At this point, we would like to introduce a case that highlights many of the treatment and medication dilemmas children and adolescents encounter.
THE CASE OF PHILLIP
Phillip is a 7-year-old first-grader from a singleparent home. His mother is on public assistance, and he is the oldest of four boys. Although some of the details of his developmental history are sparse, Phillip began to exhibit impulse control problems at the age of 2 years and 4 months, shortly after his father moved out of the house. He was hypervigilant, easily distractible, aggressive with his younger sibling, and frequently irritable. Initially, his mother believed he was going through a stage of rebelliousness, but after several months she became concerned about his behavior and mentioned this to the pediatrician. After a brief examination, the pediatrician indicated that Phillip was likely suffering from ADHD and recommended against medication unless his behavior got too out of control at home. However, she felt he would need a course of methylphenidate/ Ritalin, a prescription stimulant, once he began preschool. Phillip's mother accepted this recommendation and planned to have him evaluated when he began preschool. Phillip's behavior improved slightly over the next several months, without therapy or psychotropic medication.
When he began preschool, it took only a few days before all his active symptoms returned. After observing him for several weeks, the teacher recommended to Phillip's mother that he see a physician to be assessed for a stimulant medication. After the evaluation, the physician prescribed 10 mg of methylphenidate/Ritalin daily for Phillip. Methylphenidate/Ritlain is one of the most common stimulants used for symptoms of ADHD in children. It is intended to reduce inattentiveness, distractibility, impulsivity, and motor hyperactivity, with a goal of improved academic productivity. Phillip's symptoms slightly improved over the next eight weeks, but his aggressive behavior toward other children increased. Phillip's mother noticed more unpredictable behavior at home, as well as sleeplessness and restlessness followed by long periods of lethargy. She took him back to his physician, who referred them to a psychiatrist. The psychiatrist, after a three-session assessment, diagnosed Bipolar I (BPI) Disorder, took him off the methylphenidate/Ritalin, and prescribed 50 mg of carbamazepine/Tegretol daily and 0.01 mg of clonazepam/ Klonopin. The carbamazepine/Tegretol was used to reduce his manic symptoms. This antiseizure medication has over time been found very effective with Bipolar Disorder ( Phelps et al., 2002 ).
The clonazepam/Klonopin was used to address Phillip's anxious and agitated symptoms. This antianxiety medication often relaxes children and reduces anxiety without inducing sleep.
Many of Phillip's symptoms diminished, but his mother noticed both a sluggishness and apathy in him that were new. Over the course of the next year, Phillip's teacher addressed several of his learning and cognitive processing problems. Up to this
point, the focus of Phillip's treatment had been psychopharmacologic. No psychosocial interventions were given to Phillip, as is often the case ( Phelps et al., 2002 ). No one seemed to have any awareness or discussion about the optimal level of medication for Phillip, and there was no referral for a psychosocial assessment. As his symptoms worsened, he was evaluated by a psychiatrist schooled in prescribing adult psychotropic medications off label to children. Finally, Phillip's mother took him to see a therapist, who focused on Phillip's attachment issues, his phobic anxiety triggered by sudden loss or the anticipation of sudden loss, and his physiologic symptoms, which the therapist considered powerful side effects of the pharmacologic therapy.
Analysis of Phillip's Case
Analyzing the case, Phillip was treated by pharmacology in the medical model method and rational thinking centered on pharmacology dominated the case. The combination of methylphenidate/Ritalin and carbamazepine/Tegretol on Phillip's system was supposed to reduce some of his externalizing symptoms in the constellation of ADHD or Bipolar I disorders, but the psychological aspects of his personality were ignored. Not until much later in the course of his illness did Phillip get some assistance in those domains. Culturally, Phillip's mother had little power in society and was torn between accepting the opinion of the medical experts, and watching the negative impact the medications were having on her son. As mental health professionals, we need to understand the medical psychiatry's rapid efforts to address most disorders of childhood and adolescents with psychotropic medication. Far too often, medicating professionals view talk therapy and other psychosocial interventions as ineffective and second rate. Because medical professionals hold more power in our society than mental health professionals, their medical opinions are frequently given more weight. Today, psychiatrists burdened by enormous caseloads are open to what is known as split-treatment, a joint effort by the mental health professional and psychiatrist to plan and integrate treatment and be vigilant for client manipulation. We must integrate care into a larger model of treatment that addresses each of the four perspectives equally and where mental health professionals' opinions on mental health treatment are given more weight. In addition, the power of pharmaceutical companies must be monitored. Bodenheimer (2000) has documented numerous cases where companies prevented important research findings from being published because they were not favorable regarding the compounds being tested. To what extent may such situations affect clients like Phillip? This will be discussed later in the chapter.
Remember, Phillip was in the 4 to 7 age range when he began treatment. Coyle (2000) comments that there is “no empirical evidence to support psychotropic drug treatment in very young children and that such treatment could have deleterious effects on the developing brain” (p. 1060). Furman (1993) posited that psychiatrists in the United States are recklessly “out of control” in prescribing methylphenidate/ Ritalin and other stimulants for children, in contrast to the extreme caution that physicians in almost all European countries use in recommending this treatment approach. With the increasing trend to medicate a younger and younger population ( Zito et al., 2000 ), mental health professionals not only need to understand the impact and therapeutic effectiveness of these medications, but also their limitations and potential for harming children.
THE MEDICATION OF CHILDREN AND THE FEDERAL LAWS
As we have noted in previous chapters, the laws of the land hold great influence over cultural and social paradigms. To a large extent, laws are the result of a dynamic interaction of forces that influence other areas such as socioeconomic status and the fiscal systems of a society. Socioeconomic status and fiscal systems shape laws in very powerful ways, and people with financial resources are able to buy influence with lawmakers. This is nothing new, but bears stating in this chapter. Although recent legislation has been introduced to address
the many problems of prescribing psychotropic medications for children, most such laws require only voluntary testing of psychotropic drugs, diminishing any real impact. In this section, we summarize recent laws and comment on them, beginning with a summary in Table 9.1 .
TABLE 9.1 Major Emphases of Recent Legislation on Pediatric Pharmacology
|
|
|
|
Law/Rule |
Summary |
|
|
|
|
FDA Modernization Act (Public Law Number 105-115, 1997) |
Recognizes rights of children as patients Sets specific standards for research of pediatric drugs Encourages pediatric labeling |
|
Best Pharmaceuticals for Children Act (Public Law Number 107-109, 2002) |
Voluntary pediatric studies of currently marketed drugs Created list of all pediatric drugs needing documentation Requires timely labeling of pediatric drugs Establishes a mandate to include children of all cultures in studies Voluntary studies of new drugs |
|
Pediatric Rule Bill of 2002 a |
Required timely pediatric studies and adequate labeling |
|
|
|
|
aChild & Family Services Improvement Act: Language on how the use of medications is to be monitored. |
© Cengage Learning®
FDA Modernization Act
Buck (2000) traced the unfolding need for greater specific labeling of drugs used with patients less than 18 years of age. The burgeoning use of almost all drugs approved for children by the FDA compelled pediatric health care providers to use these drugs off label without a clear knowledge of dosing, administration, or adverse-effect information. In 1992, the FDA took steps to improve both pediatric labeling and research, which resulted in support for building a network of pharmacologic research by the National Institutes of Health (NIH). These efforts began to address the problem, and passage of the FDA Modernization Act (1997) for the first time set specific requirements to tighten regulations relating to pediatric pharmacology. This law encouraged pediatric labeling on drugs used widely with children and adolescents where the lack of labeling might lead to serious misuse. However, the FDA website (2013) warns that users of methylphenidate/ Ritalin may have an erection lasting many hours. This from an agency that still cannot conduct pediatric studies that evaluate the full impact of the drug on that population.
This law goes a long way toward recognizing the rights of children as patients, protecting their health, and assisting pediatric providers with essential information. Unfortunately, the law did not go far enough. Many practitioners and lawmakers felt the need for a comprehensive law to mandate pharmacologic research, monitor it, and further protect children.
The Best Pharmaceuticals for Children Act
On January 4, 2002, President George W. Bush signed Public Law Number 107-109, the Best Pharmaceuticals for Children Act ( Dodd, 2001 ), with the anticipation that it would address many of the dilemmas and controversies surrounding the eruption in use of pharmaceuticals for children. This law aims to initiate critical studies with pharmaceuticals already prescribed to a population for whom there exists little research, and it tightens the monitoring and development of new drugs released for children and adolescents. The law seeks to integrate viewpoints on medicating children with the medical, cultural, and social perspectives. Unfortunately, its most powerful provisions regarding the conduct of pharmaceutical companies are voluntary.
The Best Pharmaceuticals for Children Act (BPCA) has 19 sections that can be viewed at http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/ucm148011.htm ).
This law encourages voluntary pediatric studies of already marketed drugs, the so-called off-label psychotropic drugs in widespread use with children, and it creates a research fund for studying these drugs (see http://blogs.fda.gov/fdavoice/index.php/tag/best-pharmaceuticals-for-children-act-bpca/ ). Both efforts are critical to understanding the effectiveness and efficacy of psychotropic medications for children and adolescents. Further, the law establishes an ongoing program for the pediatric study of drugs, including a list of all drugs for which documentation is needed. This aspect of the law is monitored by the commissioner of the FDA and the director of the National Institutes of Health, who have the power to make written requests to pharmaceutical companies for pediatric studies. The law requires timely labeling changes for pediatric drugs under study.
As of this edition, the status of most pharmaceuticals for children and adolescents remains similar to what it was in 2006. There was the black-box effort with SSRIs and SNRIs, but they are prescribed at rates higher than in 2006 ( Cummings & Fristad, 2007 ) and most other psychotropics are used with children and adolescents to quiet anxiety, agitation, and rage.
However, the pharmaceutical companies continue to challenge the Pediatric Rule on all fronts and now it is 2014 and most important drugs for children have not been studied with a pediatric group. So goes the Pediatric Rule. On October 17, 2002, the U.S. District Court for the District of Columbia ruled that the FDA did not have the authority to issue the Pediatric Rule and has barred the FDA from enforcing it. The Pediatric Rule would have required timely pediatric studies and adequate labeling of all human drugs.
Child and Family Services Improvement Act
The Child and Family Services Improvement Act of 2011 (Public Law 112-34) includes new language that addresses the social-emotional and mental health of children who have been traumatized by maltreatment. State Child and Family Services Plans now have to include details about how emotional trauma associated with maltreatment and removal is addressed. They also have to describe how the use of psychotropic medications is monitored.
A WORD ON CROSS-CULTURAL PERSPECTIVES
Tseng (2003) proposed many variables and differences in prescribing psychotropic medications to children and adolescents from various cultures. He stressed that one must consider not only the physician's attitudes about treating people from different cultures, but also the patients' perspectives on how they feel about psychotropic medications. Thus, the giving and receiving of medications has many implications. This factor is greatly enhanced for children and adolescents, because the physician must not only communicate with the parents about the diagnosis and the psychotropic medications (neither of which may make sense in the parents' worldview) but must also weigh carefully the cultural issues that the family brings to treatment.
Tseng (2003) also addresses the enculturation issues of children. His research has described how not every culture emphasizes the fast-paced and often accelerated approach to growing up that characterizes the United States. Enculturation is defined as a process through which an individual, starting in early childhood, acquires a cultural system through the environment, particularly from parents, school, and so on. Some cultures, such as many Asian cultures, have a laid-back attitude toward babies and toddlers that is more indulgent. Yet later, they show a dramatic shift for these children, who, when they arrive at latency, the developmental period between the ages of 6 and 11 or 12, experience enormous pressure to be diligent and to achieve. Thus, as clinicians treat children and adolescents from all cultures, they need to reconsider cross-cultural adjustment and revise the psychosocial stages of Erikson (1968) , which depended on developmental understandings in a particular culture.
With the upsurge in the use of psychotropic medications, it is impossible to monitor the expected and unexpected adverse effects. Given the expanding knowledge of the varying developmental trajectories of children from other cultures, mental health practitioners and psychiatrists need to exercise further caution when prescribing psychotropic medications
for these children. Lin and Poland (1995) described in detail the remarkably large interindividual variability in drug responses and side effect profiles. This can be partially accounted for in differences of ethnicity and/or culture apart from physiological pace. Some cultures are very suspicious of medication and may delay the decision for more than a year.
Lin and Poland (1995) have made significant contributions to the understanding of cultural psychiatry and to the fact that genetic factors associated with individual and ethnic backgrounds contribute greatly to responses to medication in children, adolescents, and adults. Kirmayer and Ban (2013) note that cultural differences in self and personhood are equally important. All researchers we reviewed point to variations within the same ethnic group and variations among ethnic groups. This further complicates the integrative dilemma, which is how to view psychopharmacology and cases from the four perspectives outlined in Chapter One as well as consider important developmental lines and levels. Mental health professionals recognize that researchers have much to learn about psychopharmacology with children and adolescents, as shown by the research cited in this chapter. We need to integrate our growing understanding of cultural psychiatry with our limited understanding of how psychotropic medications work in children. The Best Pharmaceutical Act for Children (2002) provided for including in studies children from various racial and ethnic backgrounds. The law calls for studying the impact of medications on children of different cultures.
PSYCHOLOGICAL PERSPECTIVES OF CHILDREN AND ADOLESCENTS
Medicating children and adolescents for all types of psychological disorders is a solution that only reflects partial truth. The overt behaviors and symptom profile for which they receive medication may only mask the deeper psychological wounds of loss, trauma, abuse, sibling rivalry, neglect, sexual abuse, or gender conflict. Furman (2000) has indicated that if mental health professionals carefully examined the overuse of stimulants with children, they would discover a variety of conflicts and problems fueling the hyperactive behavior. These issues could include cruelty in the home, harsh toilet training, neglect, sexual abuse, delay in language development, and more.
Young children cannot address their inner conflicts without the help of a caring therapist and the modality of play therapy, yet far too often they are diagnosed with Bipolar I or ADHD and medicated in an attempt to quickly suppress their active symptoms. There should be far more effort to get the child to a therapist to uncover the underlying cause(s) of the child's anguish, but this requires resources that, at the time of this writing, lawmakers are not giving a high priority.
The American Academy of Pediatrics (2011) for ADHD makes clear that parent and teacher assessments at home and school, respectively, along with clinical review and examination by pediatrician or psychiatrist, often omit psychological assessment of the child by a mental health professional to rule out abuse, neglect, loss, sleeplessness, or other potential causes of hyperactivity or mania. In this protocol (the AAP guidance), the psychology and clinical history of the child are treated as unimportant. Many authors unfortunately support rapid assessment of ADHD children to speed up treatment with stimulant medication.
OPPOSITION TO THE CURRENT TREND OF MEDICATING
Opponents to exclusive medication treatment for ADHD, Bipolar I, and other conditions have pointed out significant regional variations in the amount of psychotropic medications prescribed to children and wide variations in regional diagnostic criteria for ADHD and other conditions ( Safer, Zito, & Fine, 1996 ; Wolraich, Hannah, Pinnock, Baumgaertel, & Brown, 1996 ). These variances have legislators and mental health advocates from various regions of the country clamoring for more judicious use of psychotropic medications with children, with more careful attention to the range of adverse effects from them, and a more formalized protocol for diagnosing ADHD, Bipolar I, and
other conditions. This protocol should go well beyond the traditional oral report from teacher to parent about a child's externalizing behavior. Opponents of psychotropic medication use in children call for a more specific and guided differential diagnosis of these disorders because the symptoms commonly overlap with Oppositional Defiant Disorder, Conduct Disorder, Major Depressive Disorder, various anxiety disorders, and many developmental disorders ( American Academy of Child and Adolescent Psychiatry, 2007 ; August, Realmuto, MacDonald, Nugent, & Crosby, 1996 ). Many researchers and practitioners still feel that ADHD in particular is a myth and that the explosion in use of the diagnosis renders differential diagnosis impotent ( Armstrong, 1997 ; Furman, 2000 ). Furman (2000) concluded,
· I have tried to trace the thinking that followed the discovery of the vastly different approaches in the United States and Europe to the management of the active or overactive child.… This thinking led to the conclusion that ADHD is not a specific disorder or pathological entity but rather a collection of symptoms that could be manifested by a child in distress, a child in conflict within himself and/or with his environment. It has no more specificity than that, and likewise methylphenidate has no specificity in producing its effects.… Suppressing these symptoms by “subduing” the child with medication hides from all the source of the child's troubles, precludes his being able to obtain mastery of his troubles through understanding, and subjects him to a false label of brain pathology. (p. 141)
Furman, now deceased, indicated that his conclusions were not new but simply ignored.
AN OVERVIEW OF PEDIATRIC AND ADOLESCENT PSYCHOPHARMACOLOGY
By the time this text has been published, only a handful of psychotropic medications will have been approved as on label for the preschool age group. Examples include methylphenidate/Ritalin, amphetamine/Adderall, haloperidol/Haldol, and chlorpromazine/Thorazine ( Zito et al., 2003 ). Methylphenidate/Ritalin is now under great scrutiny ( Zaicek, 2009 ). For preschool-age children, it is aggressive behavior that generally triggers a referral for treatment ( Bassarath, 2003 ). A few more psychotropic medications have been approved for use in older children and adolescents ( Kluger, 2003 ), but those (such as the antidepressant fluoxetine) are hotly debated because of suicidal risk. Table 9.2 lists as many medications as we were able to find with on-label approval for children.
We have mentioned the national dilemma that more children and adolescents demand psychological services each year, yet there are fewer service providers. Concurrent with this expanding problem is the dramatic increase in the use of psychotropic medications off label for a variety of mental and emotional conditions and disorders. Although this is problematic in and of itself, the focus on psychological and interpersonal factors in treating children and adolescents has dangerously diminished. Whereas it used to be common practice for child psychiatrists to choose in each case from among drug therapy—primary drug therapy and secondary counseling, or primary counseling and secondary drug therapy ( Kraft, 1968 )—today these choices are rarely discussed routinely.
Also note that DSM criteria are primarily normed on adults and are more difficult to apply with children. House (1999) has indicated that over half of the time, children who meet the criteria for one mental or emotional disorder meet criteria for other disorders as well. This multiple nature of children's problems frequently results in a polypharmacy approach and requires careful decisions by the physician and/or treating team ( Brown & Sammons, 2002 ). How carefully those decisions are made varies from setting to setting and clinician to clinician and are more random today (Leslie, 2011).
Researchers do know that the preschool years are one of the key developmental periods for maturation of the brain dopamine system, which is targeted by stimulants ( Coyle, 2000 ). The FDA-approved package insert on methylphenidate/Ritalin warns against its use with children under age 6. Given all the unknowns, many scholars and physicians are concerned about the quality and care and the current explosion of prescribing practices with preschoolers. Mental health professionals do not have enough clear evidence about how preschoolers respond to psychotropic medications, and researchers are very uncertain about the impact of such medications on the development of preschoolers. Let's examine some of the major developmental issues.
TABLE 9.2 Drugs with FDA On-Label Approved Uses in Children
|
|
|||
|
Generic Name |
Brand Name |
Dosage |
Ages |
|
|
|||
|
ADHD Medications |
|
|
|
|
Methylphenidate |
Ritalin |
10–60 mg |
6 and older |
|
Immediate Release (IR) |
Methylin |
20–60 mg |
6 and older |
|
Methylphenidate |
Ritalin SR |
|
|
|
Sustained or Extended |
Metadate SR |
|
|
|
Release (SR/ER) |
Concerta |
|
|
|
Methylphenidate |
|
|
|
|
Transdermal |
Daytrana |
10 mg/9 hours |
6 and older |
|
Dextroamphetamine |
Focalin |
5–40 mg |
6 and older |
|
Dextroamphetamine |
|
|
|
|
Extended Release |
Focalin XR |
10–40 mg |
6 and older |
|
Lisdexamfetamine |
Vyvanse |
30–70 mg |
6 and older |
|
Amphetamine/Dextroamphetamine |
Adderall |
5–40 mg |
3 and older |
|
Atomoxetine |
Strattera |
.5 to 1.4 mg |
6 and older |
|
Guanfacine |
Intuniv |
1–4 mg |
6 and older |
|
Clonidine |
Kapvay |
.1 to .4 mg |
6 and older |
|
Antipsychotics/Mood Stabilizers |
|
|
|
|
Aripiprazole |
Abilify |
2–30 mg |
For BPI 10 and older |
|
|
|
2–15 mg |
Irritability/Autism 6 and older |
|
|
|
2–30 |
Schizophrenia 13 and older |
|
Risperidone |
Risperdal |
.25–3 mg |
Autism 5 and older |
|
|
|
.5–6 mg |
BP Mania 10–17 |
|
|
|
.5–6 mg |
Schizophrenia 13–17 |
|
Olanzapine |
Zyprexa |
2.5–20 mg |
BPI/Schizophrenia 13 and Older |
|
Paliperidone |
Invega |
2.5–20 mg |
BPI/Schizophrenia 12–17 |
|
Quetiapine |
Seroquel |
50–600 mg |
BPI 10 and older |
|
|
|
50–800 mg |
Schizophrenia 13 and older |
|
Lithium |
Eskalith |
900–2400 mg |
BPI 12 and older |
|
|
Lithobid |
900–1800 |
? |
|
Neuroleptics |
|
|
|
|
Chlorpromazine |
Thorazine |
.5–200 mg Psychosis |
6 and older |
|
Haliperodol |
Haldol |
.5 to .15 mg |
Tourette's 3–12 |
|
Pimozide |
Orap |
.05–2 mg |
Tourette 12 and older |
|
Antidepressants |
|
|
|
|
Escitalopram |
Lexepro |
10–20 |
12 and older |
|
Fluoxetine |
Prozac |
10–20 |
for depression 8–18 |
|
|
|
10–60 |
for OCD 7–17 |
|
Fluvoxamine |
Luvox |
25–200 mg |
for OCD 8–17 |
|
Sertraline |
Zoloft |
25–200 |
for OCD 6–17 |
|
Amitripyline |
Elavil |
25–100 |
for depression 12 and older |
|
Clomipramine |
Anafranil |
25–100 |
for OCD 10 and older |
|
Imipramine |
Tofranil |
30–100 mg |
depression 12 and older |
|
|
|
25–75 mg |
eneuresis 6 and older |
|
Protriptyline |
Vivactil |
15–20 mg |
depression 12 and older |
|
|
Developmental Issues
For many of you, this section on human growth and development in children and adolescents is a review. Most texts on development emphasize cognitive, language, moral, and psychosocial developmental paths. We briefly consider these lines of development
and include others that are potentially affected by the ingestion of psychotropic medication. Understanding development is further complicated by the construct of developmental lines —the simultaneous occurrence of several aspects of human growth and development.
Developmental Lines
Although there are dozens of lines of human development, this multiplicity is still not a focus for mental health professionals outside of developmental studies. What should be common knowledge for mental health professionals is still peripheral to their training. For example, the Council for the Accreditation of Counseling and Related Educational Programs (CACREP) requires only one human development course for a master's degree in school or clinical mental health counseling. There may be dozens of lines of human development. These include physical development, cognitive development, emotional development, sexual development, moral development, spiritual development, kinesthetic development, socioemotional development, gender identity, and role-taking ability. These are just a few of the lines of development to which every person has access, and, for the most part, everyone proceeds through them unevenly.
The sheer number of developmental lines and the fact that most people proceed unevenly through them raise enormous, unaddressed issues for psychopharmacology. We noted earlier that scientists know very little about how brains develop and that many researchers are concerned that psychotropic medications could profoundly damage the brains of children and adolescents when taken long term. Glen Elliott, director of the Langley Porter Psychiatric Institute Children's Center of the University of California at San Francisco, noted that the current use of psychotropic medications on children “has outstripped our knowledge base . . . we are experimenting on these kids without tracking the results” ( Kluger, 2003 , p. 51). For example, even when an adolescent truly appears to suffer from Bipolar I Disorder, the sequelae of mood stabilizer side effects such as weight gain and perhaps hair loss are likely to be more devastating for a person of that age than for an adult—but there is no research on such psychological issues.
Perhaps the greatest problem of studying child and adolescent psychopharmacology from the four integrative perspectives is that whenever the issue of medicating children comes up, the only perspective represented is that of the medical model. A good example is a Time magazine cover story, by Kluger (2003) that basically explores only the medical model perspective, with only minor attention to psychological, cultural, and social issues. The same article presents a diagram showing what parts of the brain are believed to be correlated with different mental or emotional disorders. At no point in the article does the author state that these areas are hypothesized to be correlated with symptoms and there is no evidence that they cause symptoms. This remains true as of the second edition of this book.
As we have noted throughout the book, many symptoms that are psychogenic in origin register in the brain, but this does not mean the symptoms were caused by the brain. This bias toward the medical model perspective leads laypeople to assume that mental/emotional disorders, whether in children or adults, are strictly medical disorders. This assumption is not currently supported by the evidence we have been covering in this book. A full-scale multimodal approach to mental and emotional disorders in children and adolescents considers medication and possible brain pathology as only one part of the story in a very complex interaction of tentative causes and interventions.
Developmental Pharmacology
Developmental psychopharmacology is a newer area of research that studies brain development focused on brain plasticity (the brain's ability to shape itself to environmental or chemical input) and sensitive periods (during which experience can alter neural representation before hardwiring occurs) ( Carrey, Mendella, MacMaster, & Kutcher, 2002 ). Pediatric psychopharmacology is an equally young enterprise with the first published reports dated in 1937 but by the 1980s the United States
had become the world leader in medicating children ( Riddle, Walkup, & Vitiello, 2008 ).
Although these disciplines are examining development strictly from the medical model perspective, its overarching question is, “What happens in the complex process of neural development when an infusion of psychotropic medications is introduced to address particular environmental stressors during periods of accelerated brain development?” Compared to adults, children and adolescents respond to psychotropic medications in different and distinctive ways that have implications for efficacy and safety ( Vitiello & Jensen, 1995 ). The rate at which prescriptions of psychotropic medications have grown for children despite the dearth of research to support their efficacy raises the question “are we doing too much or too little?”
Epstein (2001) posited that active brain growth spurts occur stagewise in correlation with Piagetian types of development. Thus, a child who is making the transition from the sensory motor stage to Piaget's preoperational stage is in a very active brain growth stage (from age 2 to 4 years). Epstein cites Boothroyd (1997) , who noted that lexical knowledge and syntactic knowledge grow rapidly until age 4. At about 6 (from age 6 to 8), the next rapid brain growth period parallels Piaget's concrete reasoning stage, where a child begins to think logically about experienced inputs, the concrete operational stage. Epstein discussed the next brain growth period as slow (from age 12 to 14 years), a time of practicing and consolidating new networks in preparation for the next rapid brain growth stage (between ages 14 and 16 years). Psychotropics often are administered to preschoolers in the rapid growth period between ages 2 and 4 years, and to early-latency children between the ages of 6 and 8 years. Mental health professionals do not know enough about the impact of both on-label and off-label psychotropics in these rapid brain growth periods to be administering them to children and adolescents. Bramble (2003) concluded that given the changing nature of pediatric pharmacology and developmental pharmacology, this society needs a rapid expansion of pediatric research and academic inquiry into the impact of psychotropics on children's development. The second author in an extensive review of developmental pharmacology articles found only those supported fully by pharmaceutical companies or ones that cost between $29.50 and $40.00. Almost all recommended the use of a psychotropic as a first-line intervention. Interestingly, the pharmaceutical companies signed documents stating that they had no “conflict of interest.” In addition, the medications being used are only partially successful 40–50% of the time ( Rapoport, 2013 ).
Another problem with pediatric psychopharmacology is polypharmacy : the use of more than one psychotropic simultaneously, a usage that interacts with children's metabolism in a variety of unpredictable ways ( Brown & Sammons, 2002 ). Clinicians who observe children and adolescents under the influence of polypharmacy are often startled not only by the dramatic change in the clients' affective and behavioral state but also by the array of side effects they experience. Tonya, a very aggressive 12-year-old, was placed on olanzapine/Zyprexa (an atypical antipsychotic), sertraline/Zoloft (an SSRI antidepressant), lorazepam/Ativan (an anxiolytic), and valproate/Divalproex (a mood stabilizer). This combination of medications was ostensibly for what appeared to the attending psychiatrist as Bipolar I with severe agitation and aggression in the manic phase. Tonya's symptoms diminished, but her teacher noticed new ones: slurred speech, mild tics, and a constant staring off without responding when addressed. Now, rather than disrupting the class, she slept through it. Although from the perspective of the teacher and other students this was an improvement, was Tonya being helped, or was she merely medicated into submission when she might have been more fundamentally helped with assessment and therapy from a wider interpersonal perspective?
Other developmental considerations include adverse cardiovascular effects. We have many reports of sudden deaths of children and adolescents treated with psychotropic medications, including methylphenidate/Ritalin, TCAs, SSRIs, bupropion/ Wellbutrin, lithium, and most neuroleptic medications. Gutgesell et al. (1999) detailed the
cardiovascular and electrophysiologic effects of commonly used psychotropic medication, which can be deadly. Although the precise causes of the deaths have not been documented, severe heart spasms (cardiac arrhythmias) and delayed repolarization of the heart rhythm (delayed QTc interval) make the heart muscle vulnerable to possibly lethal changes (such as ventricular tachycardia). These tragedies call on mental health professionals to be vigilant and cautious when prescribing psychotropic medication. With many high-risk medications, cardiovascular monitoring is particularly important. In fact, Wagner and Fershtman (1993) recommended ECG monitoring at baseline and during drug therapy for children and adolescents who are on the medications associated with cardiovascular side effects. Brown and Sammons (2002) argued that the use of most psychotropic medication exceeds data available for efficacy, effectiveness, and safety.
Many concerns also remain related to the physiological impact on children who take psychotropic medication. One is the controversy about the impact of stimulant treatment on brain growth in children ( Bell, Alexander, Schwartzman, & Yu, 1982 ). Researchers have recently learned that methylphenidate and other stimulants decrease blood flow to selected parts of the brain, specifically the cortex area that controls conscious movement ( Zeiner, 1995 ). In a recent study ( Castellanos et al., 2002 ), the research team concluded that developmental trajectories for all brain structures, except caudal, remain parallel for children and adolescents in ADHD patients and controls. This suggested that genetic and early environmental influences on brain development in ADHD are fixed, nonprogressive, and unrelated to stimulant treatment.
However, initial brain scans of patients with ADHD showed significantly smaller brain volumes in all regions than what appeared in the brain scans of the controls. In general, because of brain plasticity (the brain's ability to shape itself), it is possible for children to be highly susceptible to a negative impact on their brain development during one period of development and less so in another period of development ( Carrey et al., 2002 ). Does treatment with psychotropic medications constitute a negative impact? These authors further concluded that researchers are only beginning to understand the long-term effect of psychotropic medication on neuron cell factors and their overall impact on brain development. All these developmental concerns or issues involve potential adverse effects for children and adolescents taking psychotropic medication.
At this point, we cover the different categories of medications used on children and adolescents. We begin the next section with a more thorough treatment of stimulant medications.
Review Questions
· • What are some of the main problems with the increase in psychotropic medication prescriptions for children?
· • What was the impact of the FDA Modernization Act and the Best Pharmaceuticals Act for Children? Name at least three changes these acts initiated.
· • What are the “developmental unknowns” that make prescribing psychotropic medications for children problematic?
SECTION TWO: STIMULANT MEDICATION
Learning Objectives
· • Understand the mechanism of action and side effects of stimulant medications.
· • Be able to discuss the type of symptoms stimulants seem most helpful for.
Even though stimulants are currently the beststudied psychotropic medication used on children, many issues regarding their use are still unresolved. Because stimulants are prescribed almost exclusively for children, we have included information on them in this chapter. Before discussing some of
the controversial issues, let's examine some background and general information on these widely prescribed medications.
Some History
The first known stimulant in the West was cocaine. It was isolated in 1859 by a German chemist named Albert Niemann and was given to Bavarian soldiers to decrease fatigue. In 1884 Karl Koller perfected its use as an analgesic during eye surgery. His assistant, a young neurologist named Sigmund Freud, was off visiting his fiancé at the time and so missed out on credit for that discovery. Freud had been personally experimenting with cocaine and wrote the paper “Uber Coca” (“On Cocaine”) prior to realizing its addictive qualities ( Freud & Carter, 2011 ). Many people in South American societies still regularly chew coca leaves with little ill effect, because unprocessed leaves are far less dependence inducing than is refined cocaine powder ( Siegel, 1989 ). Efforts to synthesize amphetamine began in 1887, when physicians believed it useful for treating asthma. This belief emerged from the use of an herbaceutical called ma huang in Chinese medicine. Ma huang is discussed more thoroughly in Chapter Ten on herbaceuticals, but for now understand that it is the ingredient ephedra that is central to the story of amphetamines. This ingredient produces the bronchial dilation that relieves the wheezing of asthma.
In the 1920s, a Chinese pharmacologist working for Eli Lilly (K. K. Chen) was working to isolate and synthesize ephedra from ma huang. He succeeded in synthesizing a compound so structurally similar to ephedra that it was named ephedrine. Although this could be taken orally, the goal for asthma treatment was a compound that could be inhaled. Gordon Alles succeeded in developing another variation of the molecule that could be delivered in an inhaler. Called Benzedrine, this variation was successful in treating asthma. Aside from treating asthma, it also seemed to induce euphoria. People soon realized they could open the inhaler and ingest the contents for what became known as “the amphetamine rush.” This also became a popular pastime on college campuses during exams. Amphetamines were experimented with to manage a number of disorders, and one of their early uses was treating children for what was described as “overactivity.”
Werry has asserted that research in psychopharmacology for children began with publication of Bradley's (1937) paper on how amphetamine seems to calm overactive children and help children with learning disabilities. The only other noteworthy investigations of the same period were studies on the effects of antihistamines on children ( Connors, 1972 ). These works are thought to be the only primary contributions to child psychopharmacology until very recently ( Werry, 1999 ).
Bradley's work reemerged in the 1960s after psychiatry began moving away from a psychodynamic model toward the biological model dominant today. Psychiatrists at that time were not well trained in the statistical methods that were becoming the norm in evaluating medications. They turned to psychologists for assistance. The psychologists emphasized the need to look at medication effects on learning and academic performance ( Werry, 1999 ). Such research has, until very recently, remained focused primarily on stimulant medication.
Research in pediatric psychopharmacology received an unintentional boost in the 1960s with the creation of a diagnosis called Minimal Brain Dysfunction (MBD). MBD was one of the several precursors to the current ADHD diagnosis. MBD was treated with stimulant medications such as methylphenidate. Although later discarded because it was too vague, the MBD diagnosis did much to lead to the development of a norm for a methodology with which to evaluate the effects of drugs, and particularly stimulants, on children.
In WorldWar II, German, British, American, and Japanese soldiers all used amphetamines, a practice still common in the U.S. Air Force to help pilots keep alert on bombing missions ( Knickerbocker, 2002 ). After World War II, the Japanese had such huge surpluses of amphetamines that they marketed them to civilians. These drugs were advertised for the elimination of drowsiness and repletion of spirit. Researchers estimate that by 1948, 5% of the Japanese population between the ages of 15 and 25 was dependent on amphetamines.
After World War II, it became evident that amphetamines have appetite suppressant qualities, and chemists tried to tease these out from the reinforcing properties that were connected to abuse. However, most of these initial efforts (such as methylphenidate/Ritalin) failed, and then the drugs were simply marketed as amphetamines.
The amphetamine molecule is a simple and highly malleable molecule that acts as the chemical template for over 50 pharmacologically active substances ( Grilly, 1994 ). Amphetamine is basically made of two compounds (isomers) labeled “L” and “D” amphetamine. D-Amphetamine is more potent and was marketed as Dexedrine. A minor modification in this molecule yields methamphetamine marketed as Methedrine. Other variations of the amphetamine molecule can produce MAO inhibitors. Modifying amphetamine to dimethoxy-methylamphetamine (DOM) produces a psychedelic compound similar to mescaline, and further modification produces the empathogen methylene-dioxymethamphetamine (MDMA, street name “ecstasy”). The latter was a promising psychotherapeutic compound until criminalized ( Eisner, 1994 ). The therapeutic effects revolved around chemically induced states of empathy, euphoria, and well-being that facilitated insights that were then to be integrated into clients' normal awareness ( Stevens, 2009 ).
Table 9.3 outlines stimulant medications used to treat ADHD in children.
TABLE 9.3 Stimulant Drugs Used to Treat ADHD in Children
|
|
|||
|
Generic Name |
Brand Name |
Type of Drug |
Daily Dose |
|
|
|||
|
Amphetamine and D-amphetamine compound |
Adderall |
Stimulant |
5–40 mg |
|
D-Amphetamine |
Focalin |
Stimulant |
5–40 mg |
|
Methylphenidate |
Ritalin |
Stimulant |
5–60 mg |
|
Lisdexamfetamine |
Vyvanse |
Stimulant |
30–70 |
|
Atomoxetinea Stratter a |
NE reuptake inhibitor |
0.5–1.2 mg |
0.5–1.2 mg |
|
|
|||
|
aAtomoxetine is not a stimulant but an SNRI (see Chapter Five ). |
© Cengage Learning®
Mechanisms of Action in Amphetamines
Amphetamines exert almost all their effects by causing the release of norepinephrine and dopamine from the synaptic vesicles into the synaptic cleft. There are different mechanisms for amphetamines to act as dopamine agonists and the number of mechanisms used depends on the type of amphetamine. There are two isomers of amphetamine, “L” and “D.” The “L” isomer amphetamine mechanisms of action include:
· • Pure reuptake inhibitor for DA
· • No presynaptic activity
· • Enhances NMDA receptor response
· • Weak block monoamineoxidase
· • 80% metabolized
· • The classic L-isomer amphetamine is methylphenidate/ Ritalin
The D-isomer amphetamine mechanisms of action are similar to those of cocaine and include:
· • Reuptake inhibition of DA (inhibit DAT)
· • Drug taken into terminal by DAT & depletes vesicles (causes DA transporter to act in reverse) thus releasing DA from the presynaptic neuron
· • Enhances NMDA receptor response
· • Weak block of monoamineoxidase (MAO)
· • Releasing NE from presynaptic neuron
Amphetamine/Dexedrine is the classic D-isomer amphetamine but is less prescribed than Adderall. Mixed amphetamine salts/Adderall includes D-amphetamine.
In a study comparing methylphenidate to cocaine, Volkow et al. (1995) noted that although the mechanisms of action and effects are similar, methylphenidate clears more slowly from the brain, which, they hypothesize, makes it less dependence inducing. Readers are encouraged to think critically about this result, because when a similar mechanism of slow clearance is invoked to defend cannabis (marijuana) as low in dependenceinducing qualities, it is often rejected ( De Fonseca, Carrera, Navarro, Koob, & Weiss, 1997 ). Either the mechanisms discussed decrease the probability of dependence or they do not. Pharmaceutical and political agendas should be separated from this debate so that people can objectively examine the issues. In previous chapters, we have listed the adverse effects of psychotropics being discussed. With ADHD, these effects are interwoven into the complex presentation of the stimulants. We ask you to consider why in the continent of Europe (an area of the world that has about the same population as the United States), stimulant medications are used with children for only about 5 to 8% of the treatment population so treated in the United States. Now let us examine the DSM-5.
ADHD Diagnosis and Assessment
According to the DSM-5, the diagnostic criteria for attention-deficit/hyperactivity disorder are
· A. Either (1) or (2):
· (1) six or more of the following symptoms of inattention have persisted for at least five months to a degree that is maladaptive and inconsistent with developmental level: Inattention
· (a) often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities
· (b) often has difficulty sustaining attention in tasks or play activities
· (c) often does not seem to listen when spoken to directly
· (d) often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions)
· (e) often has difficulty organizing tasks and activities
· (f) often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework)
· (g) often loses things necessary for tasks or activities (e.g., toys, school assignments, pencils, books, or tools)
· (h) is often easily distracted by extraneous stimuli
· (i) is often forgetful in daily activities
· (2) Hyperactivity: Six (or more) of the following symptoms of hyperactivity impulsivity persisted for at least six months to a degree that is maladaptive and inconsistent with developmental level: Hyperactivity
· (a) often fidgets with hands or feet or squirms in seat
· (b) often leaves seat in classroom or in other situations in which remaining seated is expected
· (c) often runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness)
· (d) often has difficulty playing or engaging in leisure activities quietly
· (e) is often “on the go” or often acts as if “driven by a motor”
· (f) often talks excessively
· Impulsivity
· (g) often blurts out answers before questions have been completed
· (h) often has difficulty awaiting turn
· (i) often interrupts or intrudes on others (e.g., butts into conversations or games)
· B. Several hyperactive-impulsive or inattentive symptoms that caused impairment are present before age 12 years.
· C. Several inattentive or hyperactive-impulsive symptoms are present in two or more settings.
· D. There must be clear evidence of clinically significant impairment in social, or occupational functioning.
· E. The symptoms do not occur exclusively during the course of a Pervasive Developmental Disorder, Schizophrenia, or other Psychotic Disorder and are not better accounted for by another mental disorder (e.g., Mood Disorder, Anxiety Disorder, Dissociative Disorder, or a Personality Disorder). ( APA, 2013 , pp. 59–60)
Source: Diagnostic and statistical manual of mental disorders, 5th ed., (Washington, DC: American Psychiatric Association, 2013 ).
Both the “Consensus Statement” of the National Institutes of Health (1998) and the “Clinical Practice Guidelines” of the American Academy of Pediatrics (AAP) (2011) recommend careful diagnosis of ADHD and then an appropriate and judicious use of stimulants in combination with other psychosocial treatments to address the symptoms. Epstein et al. (2010) also emphasize that children treated with stimulant medication show improvement in ratings by parents and teachers but not in their level of functioning as measured by grades. Thus they note that mental health services in addition to medication are important.
In terms of assessment most protocols recommend a neurologic exam, a consultation with a psychiatrist or psychologist who specializes in ADHD, behavioral observation reports from parents, grandparents, teachers, and other school personnel. Olfson, Gameroff, Marcus, and Jensen (2003) , analyzing national data, reported the increased rates of treatment from 0.9 per 100 children in 1987 to 3.4 per 100 children in 1997. They posited that this increase along with fewer treatments (counseling) per child was attributed to a broader awareness of the diagnosis by special educators, growth of managed behavioral health care, and increased public acceptance of psychotropic medications. But we ask, has the mushrooming of the ADHD diagnosis in children led to improved assessment and treatment?
The answer is mixed. Although some teachers, school administrators, and pediatricians rapidly diagnose ADHD in children, the NIH (1998) , the National Institute of Mental Health (NIMH) (1996 , 2000 ), and the AAP (2001) all have developed diagnostic guidelines for ADHD for years. More recently, The American Academy of Child & Adolescent Psychiatry (AACAP) (2007) released a practical, evidence-based practice parameter. In 2011 the same group released a practice guideline with expanded treatment of how to make the diagnosis and how to add psychosocial interventions to treatment ( AACAP, 2011 ). The initial guideline was again updated in 2012. In all cases, these expert societies recommend a careful evaluation by a trained psychiatrist or psychologist in conjunction with teachers, mental health professionals, and family members. They recommend an evaluation period that is not rushed, so the team can rule out other conditions that might be confused with ADHD, and which includes observation and rating scales.
In a 10-year review of rating scales assessing ADHD, Collett, Ohan, and Myers (2003) concluded that DSM IV-based rating scales can reliably, validly, and efficiently measure ADHD symptoms in youth. In this comprehensive review, the authors evaluated the validity and sensitivity of subscales on several rating scales to assess the symptoms of ADHD. The greater use of narrowband rating scales in the assessment of ADHD can supplement and complement clinical interviews and behavioral observations in the evaluation of ADHD in children and adolescents. It is now evident that reliable and valid ADHD rating scales can augment the accuracy and specificity of diagnosis.
In a comprehensive response to the Multimodal Treatment Study ( Owens et al., 2003 ), the authors sought to answer the layered question, “What do we treat in ADHD?” and “Who treats it?” based on the needs of the child and her or his circumstances ( Paul, 1967 , p. 111). Their findings were remarkable. The children least likely to respond well to a combined treatment of stimulants and milieu therapy were those with depressed parents or caregivers and severe ADHD. Owens et al. (2003) examined several outcome predictors, using nine baseline child and family characteristics. None were
predictive, but the two issues discussed earlier along with a lower IQ of the identified child correlated with an outcome less-than-favorable with the combined treatment.
ADHD Efficacy, Effectiveness, and Conundrum
ADHD has been classified as one of the externalization disorders, along with Conduct Disorder and Oppositional Defiant Disorder. As opposed to the other two, stimulant medication has been the treatment of choice for ADHD for about 25 years in the United States ( Phelps et al., 2002 ). In fact, stimulants for ADHD are the most widely researched and used medications in child psychiatry. Evidence indicates significant increase in the use of stimulants for both preschoolers and children despite the fact that the FDA approval is only for children ages 6 and older ( Brown & Sammons, 2002 ; Riddle et al., 2001 ; Zito et al., 2000 , 2003 ). The data include empirical evidence on safety, efficacy, and adverse effects.
Research demonstrates the beneficial effects of stimulants on symptoms linked with ADHD. These effects include diminished inattention, impulsivity, overactivity ( Bennett, Brown, Carver, & Anderson, 1999 ), improved classroom attention and academic efficiency ( DuPaul & Rappaport, 1993 ), and improved mother–child relationships ( Barkley, Karlsson, Strzelecki, & Murphy, 1984 ). However, with all the benefits cited for the use of stimulants with ADHD, available literature to date has not supported or demonstrated that stimulants enhance school achievement ( Phelps et al., 2002 ). Short-term efficacy studies supported the impact of stimulants on the target symptoms. From this literature, clinicians can conclude that using stimulants with children appropriately diagnosed with ADHD diminish the child's inattention, impulsivity, and hyperactivity, but do not necessarily improve his or her academic achievement. It is very possible that the child will adapt better to the demands of the classroom environment and become less externally driven. However, it would also be interesting to research whether or not stimulants improve performance in children who are not diagnosed with ADHD.
Proponents of stimulant treatment for ADHD are more convinced than ever that the disorder is passed on through heredity via the DRD4 receptor gene and that, as twin studies have suggested, up to 80% of the variance in the trait of hyperactivity/ impulsivity is now considered to be based on genetics ( Barkley, 1998 ). Peter Jaska (1998) , president of the Attention Deficit Disorder Association (ADDA), is a staunch advocate of stimulant treatment for ADHD and argues that “we cannot and will not turn back decades of scientific research on the biological basis of ADHD, medical research, educational progress, and federal disability legislation, because some people selling books claim that ADHD is a ‘myth' ” (p. 1). Both Jaska and Barkley are experts on the biological bases for ADHD derived from the medical model perspective and the resulting medication for treatment, but they seldom address intrapsychic, cultural, or social perspectives of ADHD.
Review Questions
· • What are the mechanisms of action and side effects of stimulant medications?
· • What types of symptoms are stimulants most useful for?
SECTION THREE: ADHD AND COMBINED INTERVENTIONS
Learning Objectives
· • Understand the differences between the initial, twoyear, and eight-year follow up of the MTA study group.
· • Be able to describe conditions that may be comorbid with ADHD and why this may also be a misdiagnosis.
Interventions with ADHD usually begin with assessing the child or adolescent for oral stimulant medication, because most studies have indicated short-term behavioral improvement related to the symptoms of
the disorder when stimulants are used ( American Academy of Pediatrics, 2001 ; Barkley, DuPaul, & Connor, 1999 ; Phelps et al., 2002 ). Methylphenidate/ Ritalin accounts for 90% of the prescriptions for ADHD ( Advokat, Comaty, & Julien, 2014 ). In the late 1990s studies demonstrated that Adderall (amphetamine/dextroamphetamine) is equally efficacious but methylphenidate/Ritalin is still the leader in medications used to treat ADHD.
As noted, most consensus statements on ADHD treatment recommend psychosocial interventions that assist the family as well as the person diagnosed with ADHD. These approaches include psychotherapy, cognitive-behavioral therapy, behavioral therapy, social skills training, impulse control therapy, parenting skills training, support groups, and family therapy. Each of these approaches alone or in conjunction with stimulant medication can help ameliorate some of the symptoms of ADHD and/or address some of the underlying factors affecting the person with the disorder. The American Academy of Pediatrics (2001) first treatment guideline specifically recommended behavioral therapy as the best adjunct intervention with stimulants to establish targeted outcomes and manage the child's behavior both in the classroom and at home. They also stated that if one stimulant does not work at the highest feasible dose, the physician should recommend another. Clinicians learning about pharmacology may find it helpful to remember that stimulants generally provide only relief of symptoms, thus requiring other treatment modalities and followup. In a follow-up to that Bader and Adesman (2010) recommended a list of complementary and alternative treatments for ADHD. Although the American Academy of Pediatrics did not recommend these specifically they did note that essential fatty acid supplementation is well tolerated and modestly effective.
Results of the Multimodal Treatment Study for Children with ADHD ( MTA Cooperative Group, 1999 ) demonstrated initially that stimulant treatment was slightly more effective than behavioral therapy alone, and equally effective to therapy and medication combined. It should be noted that parents preferred the behavioral therapy conditions to the stimulants-alone treatment. As with all treatment approaches for ADHD, the MTA study is not without its critics, who argue for a better match of patient with a treatment strategy tailored and selected for the individual's needs ( Green & Albon, 2001 ). When the selected management (interventions) for a child with ADHD has not met targeted outcomes, clinicians must evaluate the original diagnosis, adjust treatments and medications, and evaluate for coexisting conditions.
Another critic of the MTA study ( Leo, 2002 ) noted that the fanfare surrounding publication of the study “was nothing short of extraordinary” (p. 53). Leo pointed out that ABC News reported that results indicated drug therapy was much better than counseling for ADHD. Leo contends that the MTA study was heavily biased toward medication treatment. He claims the study's authors all had a history of strongly favoring medication, bringing their objectivity into question. He also points out that the MTA study had four groups: one received medication, one received behavior therapy, one received both, and a fourth group received no treatments from the MTA researchers but instead received standard treatment in the community. The most “robust” changes were reported in ratings by teachers and parents of children in the study. The problem with this, according to Leo, is that the investigators preselected a group of parents who believe it is acceptable to medicate children; in fact, in all cases the parents contacted the investigators to enroll children in the study. This fact, according to Leo, points to a bias in the sample.
Edwards (2002) addressed the important follow-up outcomes of studies and interventions in the wake of the report from the MTA Cooperative Group study (1999) . He recommended that a specific family-based intervention be used in a mental health setting in conjunction with pharmacologic treatment. He specifically cited Parent Management Training (PMT) as an approach that through cognitive-behavioral coaching helps parents manage their child's difficulties. Whatever the method, more physicians, researchers, and clinicians are recommending family interventions with children and adolescents diagnosed with
ADHD. The research in treatment outcomes of ADHD is complicated, and we encourage you to evaluate many strategies and interventions for your clinical work, especially those that include family/ parent strategies.
The MTA study was followed up at two years and at eight years. Here is a summary of the findings. At two years, cessation of drug treatment was correlated with significant clinical decline. Continued drug therapy was correlated with moderate decline and initiation of stimulant therapy for those in control group was correlated with significant improvement ( MTA Cooperative Group, 2004 ). So at this point again the cornerstone of treatment seemed to be with the medication. At the eight-year follow up, 33% of the subjects were still on medication (and 83% of them were on stimulants). Improvement was maintained but the group had not “normalized” meaning there were still significant achievement gaps between them and so-called “normal” controls. Thirty percent still met the DSM-IV criteria for ADHD (though one suspects more would meet criteria under DSM-5 because you only need five criteria met rather than six). Overall, medicated children did better in math and reading. There was still a significant test score gap between children in the study and the control group. Also, interestingly, approximately 30% showed signs of antisocial behavior and 25% showed signs of Oppositional Defiant Disorder ( Barnard-Brak & Brak, 2011 ; Sheffler et al., 2009). This is interesting because many specialists felt that the antisocial behavior often comorbid with ADHD was because the ADHD was untreated. It seems that there may be something else to the antisocial behavior because it seemed to persist in so many people despite their longterm treatment for ADHD.
We spoke with one interventionist who provides a learning/coaching service to children with ADHD ( Joyce Kubik, Personal Communication, April 2003 ). Kubik not only conducts specific skill-building training/coaching for ADHD children but also conducts support groups for parents. She also gives workshops for teacher in-service programs. Her overall message is that children with ADHD are capable of developing specific learning strategies that will lead to improved academic learning and success. She outlines these specific skills in her book S.C.O.P.E.: Student Centered Outcome Plan and Evaluation ( Kubik, 2002 ). The central theme of her work is to help parents and teachers find ways to help students with attention difficulties. The American Academy of Child & Adolescent Psychiatry (2001) stated,
· Research also should include the role of school and community-based professionals, as well as primary care clinicians, in delivering treatment services. Little is known about how short or long-term effectiveness varies as a function of the school and community-based professional involvement…. They should consider child and family outcomes and cost-effectiveness of care. Linking outcomes to service parameters is an important step in encouraging practice in system change. (p. 10)
In this summary statement, you can recognize aspects of the multimodal model that forms the basis of this book in analyzing and evaluating interventions with children and adolescents diagnosed with ADHD. It calls for more comprehensive research on the multiple factors that contribute to ADHD in children and adolescents and initiates the process to improve research on outcomes with this disorder.
ADHD and Comorbidity
The American Academy of Pediatrics (2001) also stressed that evaluation for ADHD should include an assessment for coexisting or comorbid conditions. The literature on ADHD identifies several psychological and developmental disorders that coexist in children with ADHD ( Biederman, Mick, Faraone, & Burback, 2001 ; Phelps et al., 2002 ; Spencer, Biederman, & Wilens, 2002 ). These disorders included conduct and oppositional defiant disorders, mood disorders, anxiety and depressive disorders, mental retardation, learning disabilities, tics, substance abuse, and medical conditions. Researchers have estimated that among children with ADHD, the prevalence rate of
Oppositional Defiant Disorder is up to 35%, Conduct Disorder up to 26%, anxiety disorders up to almost 26%, and depression up to 18% ( AAP, 2001 ). It is more difficult to estimate comorbidity rates of Bipolar Disorder, substance abuse, and tics. Most authors who discuss comorbidity and ADHD tend to discuss the issue from a pharmacologic perspective rather than a counseling perspective ( Levy & Hay, 2001 ; Solanto, Arnsten, & Castellanos, 2001 ). This is a burgeoning and complex conundrum in the treatment of ADHD. We encourage you to be alert to the great variability in children and adolescents diagnosed with ADHD and to assess for other conditions or factors.
Susan L. Andersen (2005) studied stimulants and the developing brain. She found that the effects of stimulant drugs during different stages have unique short-term, acute effects that also influence their long-term effects. Chronic, pre-pubertal exposure alters the expected developmental trajectory of brain structure and function and results in a different topography in adulthood. She also discovered that the timing of exposure (childhood vs. adolescence), the age of examination after drug exposure (immediately or delayed into adulthood), and sex influenced observable effects. Hopefully this can provide new treatment options for ADHD.
Mental health clinicians should be able to recognize the evidence recommending cautious use of stimulants with children and adolescents diagnosed with ADHD, and should remain alert to the potential for overdiagnosis or misdiagnosis of the disorder and the extensive range of comorbid/coexisting conditions. Phelps et al. (2002) summarized issues surrounding comorbidity of ADHD, ODD, and CD related to the evidence that when two or more of these disorders occur together, the prognosis is more guarded. They also addressed the hypothesis that ADHD occurs first in the child and the symptoms of impulsivity and inattention interact with the psychosocial issues of family turmoil, parental problems, and abuse factors to trigger ODD and/or CD. Clinicians need to be alert to the range of symptoms of several disorders when assessing and evaluating symptoms of impulsiveness and hyperactivity. These conditions could emanate from psychological family and environmental factors. Although the debate continues about the effectiveness of stimulant medication with ADHD, Greenhill (1998) and NIH (1998) concluded that stimulants used for ADHD children and adolescents
· 1. Producemoderate tomarked short-termimprovement in motor restlessness, on-task behavior, compliance, and academic performance.
· 2. In studies of six months or longer, children fail to maintain academic improvement or improve social problem-solving skills ( Greenhill, 1998 , p. 53).
Atomoxetine, a Nonstimulant
Recently, atomoxetine/Strattera, a nonstimulant and a selective norepinephrine reuptake inhibitor (SNRI) has demonstrated some promising results in reducing ADHD symptoms ( Brown University, 2002 ). It was approved for use in children ages 6 and older in 2003 and for maintenance treatment of ADHD in children and adolescents in 2008. Atomoxetine/Strattera is metabolized primarily through the CYP2D6 enzymatic pathways. It demonstrates an adverse event percentage of between 3.5 and 7% (poor metabolizers) in clinical trials. These adverse events include gastrointestinal problems, irritability, insomnia, aggression, and dizziness. As a nonpsychostimulant, atomoxetine/ Straterra has potential as an alternative to the stimulants now used with ADHD. As with any new medication, only time and continued research will tell if atomoxetine will improve on the side effect profile of stimulant medications.
In a very sad and disappointing statement, the status of the treatment of ADHD has not changed in seven years since the first edition of this text.
· • Children, adolescents, and adults are being diagnosed at accelerated rates.
· • The first and second course of treatment is pharmaceuticals.
· • Efforts by the FDA, legislation like the Best Pharmaceuticals for Children Act have been marginalized.
· • Limited assistance for the poor, Medicaid, wards of the county or state, orphans and other children,
· and adolescents with restricted access to quality medical care.
· • A belief still that life is better through pharma— just watch TV since the Health Care Act passed in 2009.
· • Society's intolerance for anxious, agitated, and aggressive children.
· • Large metropolitan school systems' inability to understand the impact of bullying on students with disabilities.
So with little progress, more children take the drugs and some experience improvement whereas many others graduate to more potent pharmaceuticals.
Review Questions
· • What were the differences between the initial findings of the MTA study and the two-year and eight-year follow up?
· • What does the eight-year follow-up tell us about antisocial behavior and ADHD treatment?
· • What conditions may be comorbid with ADHD and why may these be a case of misdiagnosis?
SECTION FOUR: MOOD STABILIZERS AND BIPOLAR I DISORDER IN CHILDREN
Learning Objectives
· • Be able to think critically about the problems of putting children and adolescents on medications tested on adults.
· • Be able to articulate alternatives to so-called mood stabilizing medications for children.
The DSM-5 ( American Psychiatric Association, 2013 ) provides the following diagnostic criteria for Bipolar Disorder, Single Manic Episode:
· A. Presence of only one Manic Episode and no past Major Depressive Episodes. Note: Recurrence is defined as either a change in polarity from depression or an interval of at least two months without manic symptoms.
· B. The Manic Episode is not better accounted for by Schizoaffective Disorder and is not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.
Criteria for Manic Episode
· A. A distinct period of abnormality and persistently elevated, expansive, or irritable mood, lasting at least one week (or any duration if hospitalization is necessary).
· B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
· (1) inflated self-esteem or grandiosity
· (2) decreased need for sleep (e.g., feels rested after only three hours of sleep)
· (3) more talkative than usual or pressure to keep talking
· (4) flight of ideas or subjective experience that thoughts are racing
· (5) distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)
· (6) increase in goal-directed activity (either socially, at work, or school, or sexually) or psychomotor agitation
· (7) excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).
· C. The symptoms do not meet criteria for a Mixed Episode.
· D. The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.
· E. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).
Source: Diagnostic and statistical manual of mental disorders (5th ed., Text Revision, pp. 123–125). Washington, DC: American Psychiatric Association, 2013.
We have seen in the past decade an increasing interest and shift in focus from Conduct Disorder (CD) and Oppositional Defiant Disorder (ODD) to Bipolar I Disorder in children and adolescents ( Kusumaker, Lazier, MacMaster, & Santor, 2002 ; Milkowitz et al., 2014 ). We illustrated this in the case of Phillip at the beginning of this chapter. Although in our Chapter Eight discussion of mood stabilizers we focused on Bipolar I Disorder, in this chapter we use the more general BPI, because that is the construct common to the literature on children and adolescents. Many diagnostic scholars tell us the prevalence of BPI is growing, especially in preadolescent children, with almost no gender differences ( Bland, 1997 ; Hirschfeld et al., 2003 ; Zarate & Tohen, 1996 ). The case for increased incidence is still undecided.
In the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM-5; American Psychiatric Association [APA], 2013 ), BPI is the basis of a new category, Bipolar and Related Disorders. BPI is the centerpiece of this section, which also includes Bipolar II Disorder, Cyclothymic Disorder, Bipolar Disorders related to substance use or medical conditions, and other specified and unspecified Bipolar and Related Disorders. In order to stem the tide of BPI misdiagnoses in children, Disruptive Mood Dysregulation Disorder was introduced to the DSM-5 section on Depressive Disorders. The jury is still out on whether this will reduce the false diagnosis of BPI in children ( Margulies, Weintraub, Basile, Grover, & Carlson, 2012 ) or, for that matter, how we should treat Disruptive Mood Dysregulation ( Jairam, Prabhuswamy, & Dullur, 2012 ).
There is considerable controversy regarding the appropriateness of a BPI diagnosis in children. Questions regarding the appropriateness of such a diagnosis are founded on the idea that criteria for BPI may overlap with criteria for developmental issues; other disorders usually diagnosed during infancy, childhood, or adolescence (e.g., what the DSM-5 calls Neurodevelopmental Disorders); and other problems known to affect people of all ages (e.g., depressive, anxiety, substance use, and impulse-control disorders) ( Chang, 2008 ). Further, there are currently no pediatric diagnostic guidelines for BPI in children, and it is inappropriate to use the DSM criteria for BPI because they were normed on adults ( Kowatch et al., 2005 ; Sahling, 2009 ).
One of the most problematic issues is assuming that any type of irritability or acting out is somehow related to the invalid notion of a “bipolar spectrum.” Differentiating between irritability (very common in children and adolescents) and symptoms of BPI is an ethical imperative for clinicians, particularly those working in foster care or with other children and adolescents who have no one to advocate for them ( Banaschewski, 2009 ; Sahling, 2009 ). Although published studies using functional brain-scanning technologies to investigate early-onset BPI are few, some show brain anomalies similar to those that correlate with adult BPI ( Frazier et al., 2005 ). Only longitudinal studies will answer the question regarding how predictive such anomalies are for the development of BPI because brain scans can only suggest endophenotypes that are related to vulnerability to a disorder ( Jackson, 2006 ).
The problems with the exponential increase in diagnosing pediatric bipolar disorder are many. In many children, rapid mood swings can be normal. The treatment guidelines ( Kowatch et al., 2005 ) admit that “no one can say for sure what these children will look like when they grow up” (p. 214). This is a disturbing statement because BPI, properly diagnosed, is thought to be a chronic disorder. The authors of the treatment guidelines admit that the DSM symptoms for adult mania are problematic when used for children, but then they recommend continuing to use them. Overall, the treatment guidelines fail to draw distinctions between normal children and those really afflicted with BPI ( Sahling, 2009 ).
Currently, the DSM-5 diagnostic criteria for Bipolar Disorder are used for children and adolescents without any major modifications and the features providing the best distinction between ODD,
CD, ADHD, and BPI are the presence of a flight of ideas, grandiosity, and the episodic nature of the grandiosity ( Carlson, 1996 ; Kusumaker et al., 2002 ). As we summarize the literature on BPI in children and adolescents, we learn that it is difficult to diagnose, more clinicians are recognizing its prevalence at an earlier age of onset, three tentative developmental theories are linked to it ( McMahon & DePaulo, 1996 ), and more clinicians are using antimanic medications to treat BPI in both children and adolescents.
Soutullo et al. (2005) concluded that there is an overdiagnosis of Bipolar Disorder in the United States when compared to several countries like Spain, Turkey, India, Brazil, Switzerland, Denmark, and Finland. This difference may be attributed to a relative lack of data, differences in diagnostic criteria, different levels of recognition of child and adolescent psychiatry as a true specialty in Europe, clinician bias against Bipolar Disorder, an overdiagnosis in the United States, and/or a true higher prevalence of BD in the United States. It sounds like the same case with ADHD.
Viesselman (1999) addressed the general symptoms of BPI as expansive mood, inflated selfesteem, decreased need to sleep, talkativeness, flight of ideas, distractibility, psychomotor agitation, and excessive involvement with pleasurable activities. Phelps et al. (2002) addressed the fact that BPI youth often are incorrectly diagnosed as having Schizophrenia; thus, BPIs are difficult to discern in children and adolescents because many present with an agitated depressed mood rather than mania ( Weller, Weller, & Fristad, 1995 ). Lewinsohn, Klein, and Seeley (1995) stated that pediatric clients with BPI present with more psychomotor agitation, elevated mood, increased verbalizations, inflated self-esteem, distractibility, and a decreased need for sleep. Duffy (2010) detailed with great specificity the potential genetic markers for children who might be vulnerable to inherit Bipolar I.
The treatment of choice for BPI in children and adolescents is the mood stabilizers covered in Chapter Eight . These drugs include lithium/Eskalith, Lithobid, valproate/Depakote/Depakene/Divalproex), carbamazepine/Tegretol, oxcarbazepine/Trileptal, and olanzapine/Zyprexa. Many scholars already cited in this chapter argue against indiscriminate use of these medications with pediatric populations without further study and argue for more complete awareness of the dynamics affecting the child.
Riddle et al. (2001) discussed the finding that the older antiepileptic drugs had been well researched as mood stabilizers in adults but not in pediatric populations. Campbell, Kafantaris, and Cueva (1995) have studied lithium/Eskalith, carbamazepine/ Tegretol, and valproate/Divalproex used for children with nonspecific aggression and found lithium/Eskalith was superior to placebo and to the other antiepileptic drugs in reducing aggression. One very important note: Eberle (1998) found that one type of adverse event of using valproate with girls is that of polycystic ovarian disease, which can have profound consequences for females.
In the early 21st century, children and teens are 40 times more likely to be diagnosed with Bipolar Disorder than they were in the late 20th century ( Miller & Barnett, 2008 ). As noted above there is evidence that this is due to diagnostic inflation and not an epidemic-level increase in the disorder. Geller et al. (2012) compared lithium/Eskalith, valproic acid/Divalproex, and risperidone/Risperdal in a trial called Treatment of Early Age Mania (TEAM). The response rate for risperidone/Risperdal was significantly higher (68%) than for lithium/ Eskalith (36%) or valproic acid/Divalproex (24%). Advokat et al. (2014) note that quetiapine/Seroquel and aripiprazole/Abilify are as effective as risperidone/ Risperdal. As noted in the chapter on antipsychotics though, these drugs come with severe side effects like weight gain and disruption of metabolic functions that can lead to type 2 diabetes.
In our clinical work of over 40 years, we have found that the comorbid substance use disorders were a major missing piece in several cases with children and adolescents. These clients were diagnosed with ODD, CD, or BPI and seemingly did not improve with psychotherapy or psychotropic interventions. The missing link and confounding variable was their hidden polysubstance abuse or
dependence, which exacerbated some symptoms and masked others. The links in the literature show how the onsets of BPD, ADHD, CD, or ODD become significant risk factors in diagnosing substance use disorders. It should be noted that any attempts to procure research papers on pediatric or child papers on the research topics of developmental pharmacology, ADHD, BP I, and pharmaceuticals related to these disorders published in 2013 or 2014 were sponsored by pharmaceutical companies and cost $39.00.
The following case may provide additional understanding of these complex variables.
THE CASE OF NICOLE
Nicole, a 14-year-old Caucasian girl currently living in a foster home, had just been referred to a Severe Emotional Disturbance (SED) unit in her school system. Nicole had a history of acting out, impulsivity, distractibility, conduct, and learning problems from a very early age. Initially, Nicole was referred to a specialist for her impulsivity and distractibility both at home and in preschool at the age of 4.
During the assessment, the clinician suspected a mood disorder but seemed to have more evidence for ADHD. He recommended a daily course of amphetamine salts/Adderall with behavior management therapy at home and school, focused on specific age-appropriate behaviors. At the time of the evaluation, he did not notice Nicole's intermittent scratching of her genital area. Over the next six months, Nicole showed little improvement in her symptoms and behaviors as a result of the amphetamine salts/Adderall and the milieu behavioral therapy. In fact, some of her behaviors worsened: she attacked other children, was cruel to animals, and was overtly curious about male and female genitals. After nine months, the psychologist consultant at the school recommended another neuropsychiatric evaluation and an outside therapist who would address some of Nicole's apparent psychological conflicts along with her behavior.
The second psychiatric evaluation yielded a change in diagnostic perspective. This time, the psychiatrist diagnosed BPI and prescribed valproic acid/Divalproex and a low dose of lorazepam/ Ativan, an anxiolytic. The new therapist, a female, stopped the behavior therapy and began to treat Nicole with a combination of play therapy and insight-oriented therapy. The play produced associations to remote possibilities of earlier sexual abuse and abandonment, and the insight therapy captured her already highly critical superego (obsessive thought patterns and preoccupation with sexual act) and her deep affection for the rituals of the Catholic Church. Nicole remained on this treatment regimen for about two-and-a-half years. During treatment, she never really settled down in class or at home, but her behavior and attention were slightly more manageable. (We have all had cases where there is just enough improvement from the medication to raise expectations even if the client seems not to be making progress in many important areas of her life.) Later, Nicole developed a passion for reading 7 to 10 books a week that she got from the local library. On her trips back and forth to the library, she befriended some older boys (ages 10 to 13) who offered her street stimulants at a very low cost. Nicole welcomed the friendship and experimented with the drugs (stimulants, soapers, cocaine), but was gangraped by the boys one Saturday afternoon. Overwhelmed by this horrific sexual trauma, Nicole did not speak of it to anyone. She also immediately stopped associating with the boys. Her response to this event was alternately to withdraw into a cocoonlike isolation and to become aggressive with people.
She verbally assaulted teachers and foster parents and attacked her friends and other students. She was unreachable and totally out of control. She stopped attending her therapy sessions with the counselor, but she continued to seek street drugs.
Puzzled and frustrated, the school crisis team recommended an additional psychiatric evaluation and assessment for Nicole and possible hospitalization. This triggered a series of episodes in which she ran away, had several foster and specialized school placements, a brief stay at a juvenile detention facility, one abortion, and two attempts at drug rehabilitation for her dependence on stimulants, cocaine,
and now alcohol. Somehow Nicole survived and is now in an SED classroom with a specialized social worker as an aide. She is on olanzapine/Zyprexa for psychotic mania, sertraline/Zoloft for depression and anxiety, low doses of valproic acid/Divalproex for violent and aggressive outbursts, and zolpidem/ Ambien as needed for sleep. In essence, at 14, Nicole was loaded with psychotropic medications (polypharmacy). She was referred to a new female therapist, with whom she rarely spoke; when she did, she mentioned missing her former, caring play therapist, one of the most stable objects (people) in her life. Although Nicole did attend her class regularly and her behavior was quite manageable, her teachers reported very little learning progress and a total inability to interact with her classmates. Her therapist echoed much of the same descriptions, but voiced marginal hope when she and Nicole engaged in drawing or other forms of play therapy or discussed issues related to an all-loving versus all-punishing God. The concluding remarks in her individual educational plan (IEP) at school read, “No change, few academic gains, impulsive/ aggressive behavior stabilized, little socialization, continues in counseling.”
Examining this case from our four perspectives yields some important insights and omissions. Nicole did receive a more extensive assessment early on and participated in behavioral therapy first, which is recommended by the literature ( AAP, 2001 ; Kusumaker et al., 2002 ; Phelps et al., 2002 ) followed by art therapy and insight therapy when the behavioral therapy failed. It is critical to note that the second therapist helped Nicole discuss psychological and cultural issues and learned about the pressure from her complicated feelings about her upbringing in the Catholic Church and her deep awareness of her selfcritical feelings and thoughts.
As is so often the situation with a foster child, other social and cultural pressures intervened, such as drug abuse, negative and exploitive peer relationships, and sexual trauma. It is not clear whether Nicole ever experienced sexual or physical abuse earlier in her life. The most recent team is faced with an early adolescent girl with a long history of psychotropic and psychotherapeutic treatments whose life is further complicated and traumatized by rape and drug dependence. Given the assumption that the significant others in her life—case managers, foster parents, teachers— feel she is out of control, the attending psychiatrist then addressed her range of symptoms and conflicts with a polypharmaceutical strategy. This approach numbs and tranquilizes Nicole so she is more appropriate in her various living environments but fails to address the boiling issues, anguish, and conflicts from the other aspects of her life. Treatment for Nicole should begin by recognizing the extreme complexity of her life space and developing a treatment plan and approach to gradually help her titrate off some of her medications while addressing in counseling the complex issues of abuse, drug dependence, abandonment, and loss of self that so plague her. She will need a very extended and interpersonal treatment approach if she is to recapture hope and resiliency in her life. We also would speculate about the accuracy of her diagnosis, because of the interplay of her conflicts and varying presenting problems and lack of empathy in her counseling.
Review Questions
· • What are some of the problems of putting children and adolescents on medications tested on adults?
· • What alternatives do we have to so-called mood stabilizing medications for children?
SECTION FIVE: CHILDREN AND ANTIPSYCHOTIC MEDICATION
Learning Objectives
· • Know the diagnoses for which typical and atypical antipsychotics are being used in children.
· • Be able to discuss the problems with this practice.
Schizophrenia with adolescent onset has been noted since the earliest descriptions of the disorder. Readers will recall Emil Kraepelin's initial diagnosis of a
patient as having “dementia praecox,” which means “youthful insanity.” As Russell (2001) notes, given that the disorder has been linked with adolescents through the evolution of its diagnostic forms, one might think there would be ample treatment literature regarding these populations, but there is not. Childhood-onset schizophrenia (prior to age 12) is even rarer than adolescent onset. It is estimated that maybe 1 child in 10,000 would suffer this before the age of 12 ( Remschmidt, 2002 ). The differential diagnosis must include substance-use disorders, depressive disorders with psychotic symptoms, and what DSM-5 calls other neurodevelopmental disorders like Autism Spectrum Disorder ( Androutsos, 2012 ). Even when criteria are met it is very difficult to diagnose schizophrenia in a child. The Child Psychiatry Branch at the National Institute of Mental Health (NIMH) conducted a longitudinal study of childhood onset schizophrenia. Outpatient screening accurately diagnosed 55% of the 121 cases. However, inpatient observation including medication-free observation ruled out 96 children with alternative diagnoses. Outpatient screening only accurately diagnosed 62% of this same group. The conclusion the researchers drew was that inpatient, unmedicated observation was the most accurate way to diagnose these children ( Gochman, Miller, & Rapoport, 2011 ).
In a review of controlled studies of antipsychotic agents to treat Schizophrenia, Campbell, Rapoport, and Simpson (1999) found only one controlled study of the use of these agents with adolescents and one report on their use with children younger than age 12. Therefore, Russell (2001) notes, until more research is conducted clinicians must extrapolate from adult studies to children and adolescents, which poses many risks. Although he comments this is not cause to adopt a nihilistic attitude, it does call for clinical skepticism. Russell maintains it may be true that people with early-onset Schizophrenia have more severe forms of the disorder, but this has yet to be determined conclusively and it does not mean pharmacologic treatment will not be effective. Further, early-onset Schizophrenia seems to have more severe negative symptoms, making the atypical antipsychotics a better choice if the children can tolerate the adverse drug effects ( Botteron & Geller, 1999 ).
Although few data are available regarding the use of antipsychotics with childhood psychoses, in the 20th century the neuroleptic haloperidol/ Haldol was used because it tended to be less sedating ( Andreasen, 2000 ). Because of the potential for Parkinsonian-like symptoms, this medication was often prescribed with an anti-Parkinsonian agent such as benztropine/Cogentin. Ernst et al. (1999) ; Phelps et al. (2002) ; and Riddle et al. (2001) also addressed the use of the “atypical” newer neuroleptics for children diagnosed with tics, behavioral problems in autism, psychotic illness, and nonspecific aggression. In 2004, Toren et al. ( Toren, Ratner, Laor, & Weizman, 2004 ) did a benefit-risk assessment of atypical antipsychotics in treating schizophrenia and comorbid disorders in children. They found the atypicals seemed to work better than neuroleptics and now it seems that neuroleptics like haloperidol/ Haldol are only used if the patient does not respond to an atypical. Of the atypical, risperidone/ Risperdal and olanzapine/Zyprexa seemed to improve cognitive functions and inhibit suicidal behavior. Madaan, Dvir, and Wilson (2008) noted that the FDA concluded there was enough support for using atypicals in children and approved two atypicals for childhood schizophrenia.
As we noted in Chapter Seven , evidence is mounting that atypical antipsychotics are also correlated with increased risk for diabetes and hyperglycemia and that this risk includes children and adolescents ( Koller, Cross, & Schneider, 2004 ). Research by Correll et al. (2009) confirmed these mounting suspicions. The study concluded that use of aripiprozole, olanzapine, quetiapine, and risperidone for 12 weeks all produced weight gain, and varied in lipid and metabolic parameters. The authors called for more careful monitoring of the child's health before using an atypical. Whatever medication a clinician chooses, Russell (2001) emphasizes the need for multimodal treatment that includes psychosocial interventions such as individual and family therapy, psychoeducational counseling, and social skills training.
A more common problem is raised by Pappadopulos et al. (2002) in a study that examines the range of off-label prescribing of atypical antipsychotics for aggression. These authors state that although in theory doctors seem to agree about optimal prescribing practices, in the “real world” there is wild disparity in the prescriptions written. Apparently, even the agreement between researchers and front-line doctors can be influenced by staff pressure, limited staff resources, managed care limits on inpatient stays, and the movement away from physical restraint.
Another problem that requires further debate and research concerns the notion that Schizophrenia is a wide spectrum of early-onset disorders manifesting in a variety of the disorder called “schizotaxia,” which refers to a genetic predisposition to Schizophrenia ( Meehl, 1962 ). Tsuang, Stone, and Faraone (2001) advocate treating Schizophrenia prophylactically. These authors maintain that the theoretically genetic predisposition toward Schizophrenia may be associated with reversible problems and may improve the child's quality of life. Despite this strong medical model perspective, they admit that psychosocial interventions may also work. They conducted a six-week trial of risperidone (prescribed at low levels) in six subjects identified as schizotaxic. They reported that five of the six reported increased cognitive abilities during the trial as well as greater enjoyment of social activities. Obviously, there is no way to determine the amount of placebo effect until a double-blind, placebo-controlled trial is done.
Great caution needs to be exercised here, as the implications are that asymptomatic children might be given antipsychotics in the hope that their diagnosis as schizotaxic is correct. The antipsychotic market currently amasses $5 billion a year, and many fear that the theory of schizotaxia is just another way of bending the parameters of diagnosis to help pharmaceutical companies profit from a new market. Currently, no diagnostic system in the world identifies adolescents in the phase before onset as ill, so this approach would have ramifications for the diagnosis. Ideally, the issues surrounding the politics of research and publishing described in Chapter Two , need to be more adequately addressed before any further medicating of asymptomatic populations. As Frances (2013) noted, preventive psychiatry could only work if we know the etiology of a disorder and have a safe and effective treatment for the disorder. We have neither where schizophrenia is concerned.
In Chapter Seven , we discussed neuroleptics and their affinities for different CNS receptors, their pharmacokinetics, and pharmacodynamics. Marriage (2002) spoke to our inability to predict the response of an individual patient (child or adolescent) to a typical or atypical neuroleptic. He addressed the enormous response variation, especially with adolescent males, Asians, Native Americans, and people suffering fromvarious forms of organicity. For children or adolescents exhibiting symptoms of psychosis, the longterm prognosis is poor ( Phelps et al., 2002 ), and we need to learn a great deal more about the adverse side effects of both the typical and atypical medications ( Riddle et al., 2001 ). Given the outcome of Olfson et al. (2006) National Trends Study, which indicated that children treated with second-generation medication (atypical antipsychotics) included descriptive behavior disorders (37.8%), mood disorders (31.8%), pervasive developmental disorders or mental retardation (17.3%), and psychotic disorders (14.2%), we are again reluctant to endorse atypicals as a treatment of choice for childhood psychosis.
Review Questions
· • What are some of the conditions for which children are being put on antipsychotic medications?
· • What are the main drawbacks to this practice?
SECTION SIX: ANTIANXIETY MEDICATIONS AND CHILDREN AND ADOLESCENTS
Learning Objective
· • Understand particularly how anxiolytic medications are used with children who have school anxiety.
Despite the high prevalence of anxiety disorders in children (10 to 20%), very few controlled medication trials have been conducted. In DSM-5, Obsessive-Compulsive Disorder (OCD) and Post Traumatic Stress Disorder (PTSD) have been given their own categories. Children's anxiety disorders, Separation Anxiety Disorder, Selective Mutism, Specific Phobia and Generalized Anxiety. In the late 20th century, Brown and Sawyer (1998) concluded that regarding anxiolytic medication with children, “few published empirical studies support their long term efficacy for children and adolescents” (p. 83). Bernstein and Shaw (1997) noted that psychotropic medications should not be the sole intervention but should be used as an adjunct to counseling. Interventions that facilitate active mastery are important, to prevent symptoms returning after discontinuation of medication. Little has changed and almost 20 years later anxiety disorders in children are first best treated with nonpharmacological therapies like behavior therapy, cognitive-behavior therapy, and internalizing prevention programs. House (1999) noted that children's disorders can be generally grouped as externalizing (like acting out against others) and internalizing. Internalizing often results in anxiety symptoms. Young children with anxiety disorders are more likely to be depressed and to exhibit temperamental inhibition and sleep problems ( Doughert et al., 2013 ).
The 2013 article of Rapp et al. will guide our complex study of anxiety disorders. The DSM-5 and earlier versions have really not assisted our journey to discover effective treatments for children and adolescents suffering from anxiety disorders (AD). It is the second author's opinion that there have been too many changes in the DSM related to AD since 1980. Our focus needs to shift to treatment with safe and effective outcomes. Bernstein, Borschardt, and Perwien (1996) viewed these changes as placing at risk a decade of research on childhood anxiety disorders, although Phelps et al. (2002) supported elimination of some categories of childhood anxiety disorders from DSM III-R as a research-based simplification of the categories. Although prevalence rates vary for current anxiety disorders with children and adolescents ( Botteron & Geller, 1999 ; Garland, 2002 ), incidences of Generalized Anxiety Disorders (GAD), and Separation Anxiety Disorder (SAD) are frequently thought to require both psychopharmacologic and psychotherapeutic interventions. Currently, although almost all the drugs are used off label, SSRIs such as paroxetine/ Paxil, fluvoxamine/Luvox, fluoxetine/Prozac, citalopram/ Celexa, and sertraline/Zoloft are prescribed for children and adolescents with anxiety disorders. Advokat et al. (2014) noted that fluoxetine/Prozac may be the best medication if medication is necessary. The current concern over safety of these medications for children and adolescents applies to their use in anxiety disorders as well as in depression. One of chronic side effect of SSRIs recognized in children is a behavioral activation ( Riddle et al., 1991 ), like an increased agitation different from a mania. As noted earlier the Food and Drug Administration (2003) issued a Public Health Advisory stating that use of SSRIs and similar types of antidepressants with depressed children and adolescents may be linked to increased suicide rates. How this will affect use of these antidepressants for anxiety disorders remains unclear. Rapp, Dodds, Walkup, and Rynn (2013) continued to use SSRIs in their combined treatment approaches with children diagnosed with GAD, SP, and SAD. Their study gave very high marks to Cognitive-Behavioral Therapy (CBT) in conjunction with a psychopharmacological approach.
In a review of the literature on anxiolytic medications used in pediatric populations, Livingston (1995) noted mixed results with benzodiazepines and said that in cases where studies show initial results, the results fail to be significant in replications of the studies. Livingston notes that if children are going to be placed on these medications, prescribers need to “start low and go slow” (p. 248). Recall from Chapter Six , benzodiazepines such as alprazolam/ Xanax and diazepam/Valium have an inhibitory impact on the CNS at the GABA receptor complex. As Advokat et al. (2014) note these drugs usually cause cognitive impairments and so are not recommended except in the case of shortterm medical procedures (e.g., dental procedures).
SCHOOL ISSUES, ANXIETY, AND CHILDREN
A relevant law when addressing anxiety in children is the Individuals with Disabilities Education Act (IDEA). Services to children are provided under a number of provisions in this act, and often many DSM anxiety disorders can be used to qualify a child for services. The diagnostic categories of DSM do not automatically correspond to the eligibility categories in IDEA. The interested reader can go to http://www.ed.gov/offices/OSERS/IDEA/the_law.html for a listing of the relevant diagnoses. IDEA services focus on disability conditions that interfere with a child achieving academically or vocationally.
Anxiety disorders have been used to qualify a child for special services. A key symptom is fears associated with personal or school problems that persist over a period of time and adversely affect educational performance. Anxiety disorders are one of the most common childhood disorders and may impair a child's life even if symptoms are below the threshold for a DSM diagnosis. For example, some studies show “subclinical” anxiety to be highly correlated with reading difficulty ( Bernstein & Shaw, 1997 ). Currently, studies are underway to measure the impact of bullying on anxiety ( Twemlow, Fonagy, Sacco, & Brethour, 2006 ).
Developmental differences exist in the presentation of the anxiety disorders. For example, younger children with Separation Anxiety Disorder have far more symptoms than older children. In adolescents, somatic complaints and school refusal are more common than in younger children. Conversely, older children with GAD show more symptoms than younger ones. This is probably caused by cognitive differences, because older children have more mental tools with which to craft their worries.
Interestingly, in several studies with benzodiazepines, the medicated groups did no better than placebo controls. Two studies did yield significant differences among school refusers and children with selective mutism and social phobia. In one study, the school refusers did better than controls when given Tofranil/imipramine, a tricyclic antidepressant. The other study, on selective mutism and social phobia, showed that the experimental subjects did better than controls when given Prozac.
A related childhood disorder is Separation Anxiety Disorder. Here, the anxiety is aroused by separation from familiar people (usually parents) or leaving home. The reaction is excessive and may include fears that something will happen to the parents or to prevent reunification. Somatic complaints are also common. The distinction must be made between developmentally normal separation anxiety and this disorder. If refusal to go to school is thought to be due to Separation Anxiety Disorder, the child will go if accompanied by the parent. Although benzodiazepines and antihistamines have been used to treat this ( Wozniak et al., 1997 ), exposure-based interventions and relaxation are likely to be more effective.
Another subthreshold condition is shyness. It is consistently correlated with adult and childhood anxiety disorders. Although common (90% of people report feeling it at some time in their lives), it can be debilitating as the person gets older. Shy men marry later and become parents later than their counterparts who are not shy. Although shy women marry and become parents at ages comparable to their counterparts who are not shy, they are less likely to attend college or work outside the home. Social phobia is a severe manifestation of shyness that afflicts about 5% of children. It delays social and emotional development. The overwhelming fear of doing or saying something embarrassing or humiliating keeps such people from eating, drinking, or writing in public or engaging in everyday conversations.
Although children generally outgrow shyness, they do not outgrow Social Phobia. Children with social phobias are usually depressed and lonely and almost always solitary. They may show extreme anxiety in situations where they feel they are being evaluated by others. The onset of Social Phobia is usually in adolescence and without treatment, the course is often chronic. There is high comorbidity with depression, other anxiety disorders, and substance abuse to self-medicate. As with other
childhood anxiety disorders, the recommended treatments include rehearsal, imagery, and drug treatment with antidepressant compounds. Behavior therapy has a 70% success rate for both children and adults, with systematic desensitization and exposure being the common treatments. Although more children and adolescents are being prescribed SSRIs and SNRIs for shyness and Social Phobia, there is literature supporting the practice. Rapp et al. (2013) continued to use SSRIs as the pharmacological treatment of choice in their protocols with some success and marginal adverse effects in the pediatric population. They reported on one study that used pregabalin (Lyrica) with promising results with a pediatric population. There are too many adverse effects to pregabalin.
Review Question
· • How could anxiolytics be helpful to children with school anxiety?
SECTION SEVEN: ANTIDEPRESSANTS AND CHILDREN AND ADOLESCENTS
Learning Objectives
· • Understand why the black-box warning on antidepressants for children is important.
· • Be able to suggest the type of monitoring necessary if a child is on an antidepressant.
· • Know the “placebo problem” especially in reference to children and antidepressants.
Many reports have appeared on an increased incidence of MDD in children and adolescents. Although more studies on this have begun, there is always error in the epidemiologic methods used to gather such data, so such reports are far from conclusive ( Ingersoll & Burns, 2001 ). As McClure, Kubiszyn, and Kaslow (2002b) noted, many approaches are used for diagnosing and treating mood disorders in children, only a few have any empirical support. It does seem that when identified, childhood or adolescent depression is characterized by high rates of comorbidity with conduct, anxiety and attention deficit disorders, impaired social and vocational functioning, increased rates of substance abuse, eating disorders, and higher risk for completed suicide ( West, 1997 ). Given that, it is important to consider all treatments that may be helpful when a child or adolescent does manifest symptoms of depression.
Depression (unipolar) can be very difficult to discover, discern, and diagnose in children and adolescents. In children, the symptoms manifest themselves as hyperactivity, impulsivity, and aggressiveness. Grief and loss may trigger enuresis, sleeplessness, nightmares, and extreme stubbornness, depending on the age of the child ( Brown & Sammons, 2002 ; Riddle et al., 2001 ; Ryan, 2002 ; Viesselman, 1999 ). In fact, Ryan (2002) noted that depressive illnesses in children and adolescents can be protracted, recurrent, and continue into adulthood.
Newer research into the complexities of antidepressant action can help neurologists and clinicians better understand developmentally important age differences in the nervous system. Researchers are beginning to see that developing animals differ from older ones in serotonin-mediated responses. Very-early-onset stress may compromise later adaptive capacity of some of these systems ( Goldman-Rakic & Brown, 1982 ). Juvenile depression may also differ substantially from adult depression regarding the role of noradrenergic mechanisms and thus in the responsiveness to compounds that target norepinephrine. Practitioners need to be alert to warnings such as those by Coyle (2000) , who noted there is “no empirical evidence to support psychotropic drug treatment in very young children and that such treatment could have deleterious effects on the developing brain” (p. 1060).
Tricyclic Antidepressants in Children
Overall, the results have not supported data found in adult studies regarding the efficacy of tricyclic antidepressants in treating juvenile depression
( Cohen, Gerardin, Mazet, Purper-Ouakil, & Flament, 2004 ; Rosenberg, Holttum, & Gershon, 1994 ). The weight of currently available evidence suggests that TCAs as a group are indistinguishable from placebo, except in side effects ( Kutcher et al., 1994 ; Puig-Antich et al., 1987 ). The highest response rate in a study is about 44%. In addition, a significant risk arises of serious cardiac problems in developing bodies. The same conclusions hold true for the TCA derivatives such as desipramine/Norpramin and nortriptyline/Trazodone. Both have been fairly well studied, and researchers have failed to show significant therapeutic differences from placebo but did show a high number of adverse side effects. In addition, both still carry the risk of cardiovascular complications.
Research has demonstrated that TCAs (and MAOIs) have not revealed greater efficacy than that for placebo, and their adverse side effect profile is extensive, including reports of sudden cardiac death ( Birmaher, 1998 ; Brown & Sammons, 2002 ; Kye et al., 1996 ; Riddle, Geller, & Ryan, 1993 ; Werry, 1999 ). There is little support if any for the routine use of TCAs as a first line of treatment in children and adolescents. Therefore, it is disturbing that millions of prescriptions for desipramine and related compounds have been written for young people under age 18 ( Goleman, 1993 ). Sommers-Flanagan and Sommers-Flanagan (1996) recommended that such prescriptions be reserved for special cases where other treatments have proven ineffective or intolerable and that a thorough physical (including cardiovascular exam) should be conducted before beginning the medication. TCAs should be used in children only under the following conditions:
· • Full informed consent of patient and parent
· • A history of lack of response to more appropriate treatments
· • Full disclosure of side effect profile
· • Disclosure of cardiotoxicity of these compounds
· • When trials of more effective, available pharmacotherapies (SSRIs) have failed
Also, TCAs should be used with extreme caution, because the noradrenergic system (on which TCAs operate) does not fully develop until early adulthood ( Goldman-Rakic & Brown, 1982 ). This evidence has not changed.
SSRIs in Children
As noted, the FDA (2003) has currently issued a Public Health Advisory cautioning about a possible link to the use of certain SSRI antidepressants in pediatric populations and increased suicide rates. The antidepressants in the advisory are listed in Table 9.4 .
As noted, the SSRIs currently are used with children and adolescents for anxiety and depression. Fluoxetine/Prozac has received FDA approval for use in pediatric populations, and fluvoxamine/ Luvox is approved for treating OCD in children ( Brown & Sammons, 2002 ). All other SSRIs are prescribed as off label to children with depression as of this writing. Children and adolescents encounter the same adverse effects as when the SSRIs are employed with anxiety disorders. These compounds are more effective in children but not as effective as in adult samples. Glaxo-SmithKline pled guilty to criminal charges for promoting paroxetine for use in the pediatric agerange for the treatment of depression ( Hensley, 2012 ).
TABLE 9.4 Antidepressants Listed in 2003 FDA Public Health Advisory
|
|
|
|
Generic Name |
Brand Name |
|
|
|
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Fluoxetine |
Prozac |
|
Fluvoxamine |
Luvox |
|
Citalopram |
Celexa |
|
Escitalopram |
Lexapro |
|
Mirtazapine |
Remeron |
|
Nefazodone |
Serzone |
|
Paroxetine |
Paxil |
|
Sertraline |
Zoloft |
|
Venlafaxine |
Effexor |
|
Bupropion |
Wellbutrin |
|
|
© Cengage Learning®
It is important to note that adolescent girls are particularly vulnerable to depression when entering puberty ( Phelps et al., 2002 ; Silberg et al., 1999 ). Clinicians should be sensitive to gender, family history of depression, impacting life events, loss, or death when assessing children for depression. Current trends and preliminary understandings of the research suggest that in addressing childhood depression, the clinician must consider both psychotherapy and medication ( Badal, 1988 , 2003 ). Ryan (2002) indicated that 30 to 40% of children do not have a sufficient response to the first SSRI treatment.
There is almost no literature on the effects of SSRIs on infants and preschoolers ( McClure, Kubiszyn, & Kaslow, 2002a ); however, evidence shows SSRI prescriptions are on the increase for this age group ( Zito et al., 2000 ). The majority of researchers looked at the effects of fluoxetine (Prozac) on older children and adolescents, which has shown mixed results ( Emslie et al., 1997 ). Some studies looking at the effects of paroxetine on children and adolescents are also promising ( Findling et al., 2000 ; Keller et al., 2001 ), but more doubleblind, placebo-controlled studies need to be done. Juveniles with a family history for manic or hypomanic symptoms are at higher risk for SSRIinduced manic or hypomanic episodes. If children or adolescents are treated with SSRI medications, treatment should be cautious and should observe the following conditions:
· • SSRIs are used in addition to supportive psychotherapy or counseling to deal with psychological issues.
· • SSRIs should be supported by education regarding the symptoms, the medication, and what relief the medication is to provide.
· • Effective treatment involves parents or caregivers as much as possible.
· • Effective treatment includes use of a depression scale (HAM-D or BDI-II) if the child is old enough to take one, to monitor symptoms.
· • The acute phase of treatment should take place over 8 to 12 weeks followed by maintenance of 4 to 6 months.
McClure et al. (2002a) conclude that when medication is warranted, the SSRIs are the medication of first choice. Jureidini et al. (2004) disagree, however. They recently reviewed and critiqued seven published randomized, controlled trials of newer antidepressants for depressed children. These researchers found that pharmaceutical companies paid for the trials, the benefits of the drugs were small, and the adverse effects were downplayed, and they concluded antidepressant drugs could not be confidently recommended as a firstline treatment option. This is only one metaanalysis, but it points to the need for validity in published data and full disclosure of biases resulting from funding sources or researchers. Karger (2013) concluded that SSRI and even SNRI treatments for pediatric populations were/are too risky and this is from an international perspective. He stated that the SSRIs were more effective with anxiety disorders. Studies have been more compromised in pediatric populations with depression. Also, Craighead, Miklowitz, and Craighead (2013) summarized the work of Dr. Du of Shanghai who indicated that his studies demonstrate that SSRIs are safer in adolescents than in children. Dr. Du encouraged universal efforts of prevention to address the 17–20% of children who are depressed in all of our cultures.
From an integrative perspective, it is important to review all literature as it comes in, as well as review the researchers and the funding sources to check for possible bias. At the time of this writing, a new government-funded study of SSRIs and children was completed but not officially released in a peer-reviewed journal. The study was the Treatment for Adolescent with Depression Study (TADS), sponsored by the National Institute of Mental Health (NIMH). When we called NIMH to get a copy of the study, we were told the study needed to be peer-reviewed and the results would not be released until that process was complete. Nevertheless, Time magazine ( Lemonick, 2004 ) and The New York Times ( Harris, 2004 ) reported
(without benefit of peer review) that the study supported the use of the medications with children. When we asked the NIMH representative how the popular press would have gotten the results to report before the peer review, she said she didn't know. Until a peer review of the study is concluded, the writers have no basis for these conclusions other than their own opinions of the study. Without including the results of peer review, readers are likely to come away with a “sound byte” interpretation of the results that may not be accurate. Readers can access the latest results of drug trials on the NIMH website http://www.nimh.nih.gov/studies/2mooddisordersdep.cfm . We did not try for the results in 2014.
THE PLACEBO PROBLEM
As we noted in Chapter Five , the placebo effects of compounds and the place and type of placebo in studies has yet to be explicated. According to Fisher and Fisher (1997) , “A probe of the available scientific reservoir of pertinent studies does not reveal any serious evidence that antidepressants do more for childhood depression than do placebos” (p. 308). An earlier overview of studies by Thurber, Ensign, Punnett, and Welter (1995) concluded that the more adequate the experimental methods in each study, the less likely to be found superior to placebo were the drugs tested. Although Fisher and Fisher (1997) noted that the evidence is still limited for the effectiveness of many counseling/psychotherapy approaches to depressed children and adolescents, this does not excuse the prescribing of compounds for which very little evidence of efficacy and effectiveness exists.
In concluding this section, we remind the reader that clinicians are using off-label psychotropic medication for several other disorders. In each case, the clinician must weigh the benefit versus the potential adverse effects of the drug on the child. We must also speak to the child about his or her reaction and feelings about the medication and request feedback from the parents or guardians about the child's progress or struggles with the psychotropic medications. We believe it is an enormous responsibility to counsel children and adolescents who are on psychotropic medication where little research has been conducted on the efficacy, effectiveness, and safety of the drugs.
In April 2003, the recommendations were published of the Research Forum approved by the American Academy of Child and Adolescent Psychiatry (AACAP) on strategies for psychopharmacological studies on preschool children ( Greenhill et al., 2003 ). The six workgroups of the Research Forum were (1) diagnosis/assessment, (2) research design, (3) ethics/institutional review board (IRB), (4) preschool protocol modifications, (5) FDA/regulatory industry, and (6) training/public issues. Finally, when our text was reviewed in 2005, most psychiatrists challenged us on our strident positions about pharmaceutical research, medicating children, split-treatment (working together—psychiatrist and mental health professional), and the general tone of our text. Now we wish to extend our empathy to all psychiatrists who work under tremendous pressure to cure the incurable and find the magic pill.
Review Questions
· • Why is the black-box warning on antidepressants for children important?
· • If a child is put on an antidepressant, what sort of monitoring is necessary for the child?
· • What is the placebo problem with regard to children and antidepressants?
CONCLUSION
We have sought to highlight the complexity, controversy, and conundrums of child and adolescent psychopharmacology. By now, you are alert to factors from all four perspectives that impinge on this issue, generate “word magic,” provide partial truths, or stimulate errors. In the colossal debate over ADHD, we discover not only errors but an inflexibility that may harm children rather than treat them. We recognize the power and influence of the pharmaceutical companies to market so many “off-label”
psychotropic medications to children and adolescents with such confidence or, more accurately, grandiosity. Central to this dilemma are the shortages of mental health professionals and psychiatrists who exclusively treat children and adolescents. This shortage, coupled with the growing confidence of the effectiveness of psychopharmacology with some diagnoses, permitted pharmaceutical companies to market “off-label” drugs for children and adolescents on a grand scale while clinicians observe the phenomenon, almost powerless. Even the passage of the Best Pharmaceuticals Act for Children 12 years ago is not enough to slow this trend.
SUMMARY
The use of psychotropic medications with children and adolescents is very complex. Clearly there is no simple answer to this dilemma. Because most of the medications are prescribed off label, it is important that mental health professionals learn all that they can in order to protect the health and well-being of their clients who are children and adolescents. The information provided here spans the four perspectives to challenge the reader to consider medical, psychological, cultural, and social paradigms. The discussion of stimulant medications serves as a template for practitioners as they consider psychotropic applications with other disorders. When children or adolescents are placed on a psychotropic, it is always recommended that they receive counseling or other supportive services. The federal government through recent legislation is emphasizing how important and critical this issue is. Finally, the question is asked, “Do we as a society use psychotropic medication as the ultimate modality of behavior and anger management?”
CITING FOR THESE PAGES 224-259
Ingersoll, R. E., & Rak, C. F. (2016). Psychopharmacology for mental health professionals: An integrative approach (2nd ed.). Boston, MA: Cengage Learning.
