Community Variance and the Police Worksheet

Special Report Coniorbidiücs, Piut 1 26 Category 1 CMEPhaniiacological Changes in the Elderly 31 In MemoriamA Word From Sandy Hook

PsychiatricTiines A UBM Medica Publication" www.PsychiatricTimes.com January 2013 • VoL XXX, No.1

New Claims and Findings for Ketamine in Severe Depression

by Arline Kaplan

Emerging research generally supportive ofketamine's rapid antidepressant effects hasencouraged a few clinicians to prescribe the drug for their severely depressed, suicidal, and hospice-care patients, with reportedly good results.

"For the most part, the ketamine story and the excitement surrounding it is derived from re- search studies at the NIMH and Mount Sinai School of Medicine," said David Feifel, MD, PhD, Professor of Psychiatry at the University of California, San Diego (UCSD) and Director of the Neuropsychiatry and Behavioral Medicine Program.

Ketamine is an FDA-approved anesthetic used in human and veterinary medicine. It is a high- affinity, noncompetitive NMDA-glutamate re- ceptor antagonist that may also stimulate other receptors. It is classified as a Schedule III non- narcotic controlled substance and, at higher doses, is sometimes abused as a street drug called "Special K."

In a recent article, Murrough and Chamey' wrote that ketamine "appears to be effective at reducing the range of depressive symptoms, including sadness, anhedonia, low energy, impaired concentration, negative cognitions, and suicidal ideation."

Carlos Zarate Jr, MD, and his team from the NIMH's Fxperimental Thera-peutics and Pathophysiology Branch, along with NIMH- sponsored researchers, have conducted studies exploring ketamine's rapid antidepressant effects among treatment-resistant depressed patients with either MDD or bipolar disorder." The drug might work, in part, they suggest, by strengthening neural connections."*

Recently, Zarate and colleagues reported that ketamine produced the fastest, strong- est, and longest-lasting anti-suicidal inter- vention ever demonstrated in a controlled trial. In a replication of an earlier study, the researchers confirmed that ketamine not only lifts depression but also reduces suicidal

(Please see Ketam'me, page 4}

Police Encounters With the Mentally 111 After Deinstitutionalization

by Jonathan Barker. MD

The nation's 3 largest mental healthfacilities are Los Angeles CountyJail, Rikers Island, and Cook County Jail.' The authors of one study

estimate that using the most conser- vative numbers, as of 2004 the total number of persons in jails and prisons in the United States with a severe mental illness was at least 321,884. This number includes approximately

l-'iMllillil'IMl'lM l l ' T H

8T0

t?S890 i O '>i|EflW0N '

10% of jail inmates, 18% of state prison inmates, and 16% of federal prison inmates.-

More recent data from the Bureau of Justice Statistics show that the number of persons under the supervi- sion of adult correctional authorities declined by 1.3% during 2010, reach- ing 7.1 million at the year's end.^ The report notes that approximately three- quarters of the decline in the total correctional population (down 91,700) during 2010 was attributed to the decline in the number of probationers (down 69,500) during the year How- ever, the report does not make note of the effect of this decline on the relative number of inmates with severe mental illness compared with those without

fP/ease see Deinstitutionalization, poge 10)

Issue Highlights

Ketamine, Cum Grano Salis

Ronald Pies, MD

Update on Adolescent Mood Disorders

Karen Dineen Wagner, MD, PhD

Planek's Law of Generations

S. Nassir Ghaemi, MD, MPH

The Older Psychiatrist in an Era of

"Unprecedented Change" James L. Knoll IV, MD

COMPLETE CONTENTS, PAGE 4

10 PSYCHIATRIC TIMES JANUARY 2013 www. psych iat riet i m es.com

Ketamine Continued from page 4

the median time to relapse after the last ketamine infusion was 18 days.

The median time of 18 days, Feifel said, was disappointing, so he has not adopted the intense infusion se- ries approach, but rather a mainte- nance strategy. "At this point . . . if a patient responds well to the first infusion and gets at least a week of solid benefit, then I am willing to do repeated treatments as frequently as every 2 weeks," he said. "We have had a handful of patients undergo repeat treatments." Those patients, according to Feifel, have experienced "a profoundly improved quality of life and renewed hope."

"When you start off feeling abso- lutely miserable and fighting the urge to end your life every single day, it is a momentous change in your world, when you can know that 50% of your days are going to be depres- sion-free."

Feifel said he hasn't seen any signs of abuse or dependency from the infusions. "I haven't had a single patient pushing for another infusion while the antidepressant effect is working," he said, adding that some patients have asked to push back their scheduled treatment when they have not felt the need for it.

Asked about delivery of ketamine in other forms, Feifel said there are 3 others—oral, intranasal, and intra- muscular. "My experience is that the oral and the intranasal don't seem to have the dramatic effects of the IV infusion," he said. "IM, on the other hand, seems to be very promising. I've been able to convert some pa- tients from IV to IM maintenance, which is a much more practical, cost- effective way of administering it."

Inpatients and hospice Ketamine is particularly useful for hospitalized depressed and suicidal patients and usually allows for faster discharge. "Ketamine offers patients who are in the hospital with a severe exacerbation of their depression an opportunity to receive an interven- tion they can't normally get in an office visit," Feifel said. Ketamine is also starting to be used at UCSD Medical Center for patients on the medical/surgical floors whose pro- found depression may be interfering with their medical treatment or their ability to consent to treatment.

At San Diego Hospice and the Institute for Palliative Medicine, another UCSD-affiliated psychia- trist, Scott Irwin, MD, PhD, and his team are evaluating the efficacy and

tolerability of oral ketamine for depressed hospice patients. "These are hospice care patients who meet the criteria for clinical depression— about 15%ofthepatientpopulation," he said. These patients don't have the 12 weeks to try a standard anti- depressant, and if you look at the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) trial, 70% of people failed to achieve remission after 12 weeks on a stan- dard antidepressant."

Irwin said they use psychostimu- lants as first-line treatment for hospice patients with MDD, but if there is a significant anxiety compo- nent, they often use ketamine. "With ketamine, we are finding about a 70% response rate for depression and 100% response rate for anxiety."

In 2010, Irwin and Iglewicz* published a report of oral ketamine given to 2 patients in hospice care. Recently, Irwin and his team con- ducted an open-label trial involving 14 patients, which is in the process of being published. Overall, oral ketamine has been given to some 50 patients. The oral drug is given daily, usually at night. The patients are at home or in a hospice unit. Accord- ing to Irwin, there are few adverse effects—sleepiness is the primary side effect.

Irwin said that numerous changes have been seen in the patients, and the changes are quite dramatic. "People who weren't getting out of bed are getting up and doing produc- tive things. They are re-engaging with their families, and they are focusing on things they want to accomplish before they die."

Editor's note—We invite you to read Dr

Ronaid Pies' commentary, "Ketamine,

Cum Grano Salis," on page 11. Drs

Feifei and invin report no contacts of

interest concerning tiie subject matter

of ttiis artide. Or Zarate is Usted as a

co-inventor on a patent appiication for

the use of ketamine and its metabolites

in ma-jor depression. Dr Zarate has as-

signed his rights in the patent to the US

government but wiii share a percentage

of any royaities that may be received by

the government

References

1. Murrough JW, Charney DS. Is there anything really novel on the antidepressant hori2on? Curr Psychiatry Rep. 2012;14:643-649. 2. Zarate CA Jr, Singh JB, Carlson PJ, et al. A ran- domized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63:856-864. 3. Luckenbaugh DA, Ibrahim L, Brutsche N, et al.

Family history of alcohoi dependence and anti- depressant response to an N-methyl-D-aspartate antagonist in bipoiar depression. Bipolar Disord. 2012;14:880-887.

4. Duncan WC, Sarasso S, Ferrarelli F, et al. Con- comitant BDNF and sleep siow wave changes indi- cate ketamlne-induced plasticity in major depressive disorder Int J Neuropsychopharmacoi. 2012 Jun 7:1-11; [Epub ahead of print].

5. Zarate CA Jr, Brutsche NE, Ibrahim L, et al. Repii- cation of ketamine's antidepressant efficacy in bipo- iar depression: a randomized controlied add-on trial. Biol Psychiatry. 2012;71:939-946.

6. Covvey JR, Crawford AN, Lowe DK. intravenous ketamine for treatment-resistant major depressive disorder Ann Pharmacother 2012;46:117-123. 7. Murrough JW, Perez AiVI, Piilemer S, et al. Rapid and ionger-term antidepressant effects of repeated ketamine infusions in treatment-resistant major de- pression. Bioi Psychiatry. 2012 Jui 26; [Epub ahead of print].

8. irwin SA, igiewicz A. Orai ketamine for the rapid treatment of depression and anxiety in patients re- ceiving hospice care. J Palliât Med. 2010;13:903- 908. •

Deinstitutionalization Continued from page 1

severe mental illness. In contrast to the rising number

of persons suffering from serious mental illness in our correctional systems, from 1955 to 1994, the number of psychiatric patients being treated in the nation's public mental institutions dropped from 558,239 to 71,619.^ This drop in numbers is all the more telling when considered in comparison with the country's increase in population from 1955 to 1994.

The closing of large state mental institutions was spurred partly by the belief that psychiatric patients would fare better if treated in the community rather than behind institutional walls. If we are to hold to this belief, then mental health professionals, policy makers, and law enforcement offi- cers are obliged to think, and then think again, about how we can best serve the large numbers of persons suffering from serious mental illness now moving from behind hospital walls to behind bars, to open streets, and back again.

There are 2 primary areas for improvement. The first is diverting persons with mental illness away from jails and prisons, and into treat- ment. The second is expanding the services and treatment centers in the community.

The deinstitutionalization move- ment began in the late 1950s after the first antipsychotic medication was introduced. This psychiatric advancement, among other complex fiscal and legal factors, resulted in an exodus of psychiatric patients into the streets and communities of America, which, in turn, caused law

enforcement to have a much greater interaction with persons who had a serious mental illness. A report by the Treatment Advocacy Center and National Sheriffs' Association states that in 2004 there was approximately one psychiatric bed available for every 3000 persons in the United States, in contrast to 1955, when there was one psychiatric bed avail- able for every 300 persons.'^

The increased number of persons suffering from serious mental illness in the community today sharpens our focus on the rights of persons to not be held against their will in mental institutions without clear and convincing evidence to justify civil commitment. We have also learned from experience that the potential pitfalls of attempting to treat per- sons suffering from serious mental illness in the community includes the risk that many of them fall out of treatment, and the current system is too strained to accommodate the large numbers of people that need treatment. These factors, in turn, lead to an increased burden on the police who are called to respond to psychiatric emergencies in the com- munity, which could be better re- solved with adequate psychiatric care instead of incarceration.

An ever-increasing number of persons who have a serious mental illness are being treated in jails and prisons. To successfully achieve di- version, we should provide more training in mental health to first responders. We should employ more mental health professionals to work with the police and other first re- sponders. These efforts would be a cost-effective way to divert persons suffering from serious mental ill- ness from correctional systems into treatment.

Police officers should receive proper training, education, and ser- vices to interact with persons suffer- ing from serious mental illness in a safe manner. A report by the US Department of Justice noted incon- sistent research findings on the use of force by police when dealing with persons who have a mental illness. The authors of this report call on further research to investigate how training police can reduce use of force on persons who have a serious mental illness.''

What are the best law enforcement models for encountering a psychi- atric emergency? Models include police officers with specialized train- ing in mental health as first respond- ers to a psychiatric emergency, civilian mental health professionals employed by police, and mobile community-based mental health

JANUARY 2013 PSYCHIATRIC TIMES 11 www. psych ¡at riet i m es.com

teams that respond to police calls but are not employed by police.'

Dr Linda Teplin* points out that police officers have 3 choices when they encounter a person who has a mental illness who is creating a dis- turbance: transport the person to a hospital, arrest the person, or attempt to resolve the crisis on the street. Police officers often serve as the gatekeepers who ensure that persons

. with serious mental illness receive treatment and are not simply punished for having a mental illness by being sent to the correctional system.

If we are to entrust police officers with the responsibility of making the correct decision about the need for transport to a treatment center versus no treatment, we must provide the proper services and training to make the process efficient and safe, for both the officers and the persons with the serious mental illness. Mental health professionals, state- run forensic services, and law en- forcement agencies need to come together and discuss the most effi- cient and safe models when confront- ing psychiatric emergencies to im- prove and expand these practices across America.

Dr Barker is a fourth-year psychiatry resident

at the Tufts PJiedicai Center in Boston. He re-

ports no confiicts of interest concerning the

subject matter of this article.

References

1 . National Public Radio. Nation's Jails Struggle With

Mentally III Prisoners. September 4, 2011. http://

www.npr.org/2011/09/04/140167676/nations-Jails-

struggle-with-mentally-ill-prisoners. Accessed De-

cember 12,2012.

2. Lamb HR, Weinberger LE, Marsh JS, Gross BH.

Treatment prospects for persons with severe mental

illness in an urban county Jail. Psychiatr Serv. 2007;

58:782-786.

3. Glaze LE. Correctional populations in the united

States, 2010. December 2011. http://b]s.ojp.usdoj.

gov/content/pub/pdt/cpusi O.pdf. Accessed Decem-

ber 12,2012.

4. Deinstitutionalization: a psychiatric "Titanic."

1997. http://www.pbs.org/wgbh/pages/frontline/

shows/asyiums/special/excerpt.html. Accessed De-

cember 12,2012.

5. Torrey EF, Kennard AD, Eslinger D, et al. More men-

tally ill persons are in jails and prisons than hospitais:

a survey of the states. May 2010. http://www.

treatmentadvocacycenter.org/storage/documents/

finaUaiis_v_hospitals_study.pdf. Accessed Decem-

ber 12,2012.

6. Adams K, Alpert GP, Dunham RG, et ai. Use of force

by poiice: overview of national and locai data. Octo-

ber 1999. https://www.ncjrs.gov/pdffiles1/nij/

176330-1 .pdf. Accessed December 12,2012.

7. Steadman HJ, Deane MW, Borum R, Morrissey JP

Comparing outcomes of major models of police re-

sponses to mental health emergencies. Psychiatr

Sem 2000:51:645-649.

8. Tepiin LA. Keeping the peace: police discretion and

mentally ill persons. Nati Inst Justice J. 2000;7:8-15.

https://www.ncjrs.gov/pdffiles1/jr000244c.pdf. Ac-

cessed December 14,2012. •

Ketamine, Cum Grano Salis

T he findings reported in Arline Kaplan's article onketamine (which starts on page 1 of this issue), arecertainly exciting, particularly for those of us whohave attended the considerable suffering of many patients with treatment-resistant depression (TRD). TRD has been defined in various ways, but recent opinion has considered TRD as depression that has responded inade- quately to at least 2 trials with antidepressants from differ- ent pharmacological classes, with adequate dosage, dura- tion, and adherence to treatment.' TRD may occur in as many as 60% of depressed patients,^ and effective remedies are hard to come by. If the early and encouraging ketamine findings are borne out in large, randomized, double-blind, controlled studies, this will represent a significant advance in our treatment options for MDD.̂

And yet, there are several reasons for taking the ketamine findings with a substantial grain of salt. First, there is history. Those of us who have been treating mood disorders for the past 30 or more years have seen many "amazing new remedies" fizzle out, once tested in carefully controlled trials. This is not to diminish the importance or integrity of the keta- mine research thus far. It is only to say that the number of ketamine- treated patients is still small; the duration of study, quite short; and the durability of ketamine's apparent benefits, limited to a few weeks. Notably, to my knowledge, there have been no controlled studies comparing ketamine (via infusion or other modality) with an active control

, (ie, a drug that produces some al- teration in consciousness beyond the placebo effect of saline). It is encouraging, however, that such an active-control study is under way at New York State Psychiatric Institute, in which depressed participants are randomly assigned to receive a single intravenous dose of either ketamine or midazolam (a short-acting benzo- diazepine with pronounced amnestic effects)."

I also wonder whether the in- formed consent process for keta- mine treatment has included a dis- cussion of alternative treatments known to be effective for TRD; for example, electroconvulsive therapy (ECT). Yes, I'm well aware that ECT carries its own risks (including cog- nitive side effects) and that there are many administrative and psycholog- ical barriers to its availability. Never-

theless, ECT is "acknowledged as the most effective acute treatment for severe mood and psychotic disor- ders."' Surely, a patient with severe, treatment-resistant MDD should be apprised of ECT as an alternative to a ketamine trial, if consent is to be fully "informed." And, in my view, other agents with well-documented efficacy in TRD—such as adjunctive lithium or triiodothyronine (T,)''— should also be included in the in- formed consent process, assuming the patient has not already tried these agents.

Einally—though this may surprise some who consider "treatment" in psychiatry to include only somatic therapies—there are also good rea- sons to consider psychotherapy in some nonmelancholic, nonpsychotic cases of TRD." Although studies are quite limited and methodologically flawed, one recent review concluded that "primary care providers should consider psychotherapy when treat-

by Ronald Pies, MD

ing patients with treatment-resis- tant depression."*

All that said, I well understand that some TRD p a t i e n t s a r e acutely suicidal and may not bene- fit quickly from "established" treat- ments that require weeks or months for full effect. In such cases, and after a thorough informed consent process (which is more than signing a "form"), a ketamine trial may indeed be worth considering.

References

1. Berlim MT,Turecki G. Definition, assessment, and

staging of treatment-resistant refractory major de-

pression: a review of current concepts and methods.

Can J Psychiatry. 2007;52:46-54.

2. Fava M. Diagnosis and definition of treatment-

resistant depression. Bioi Psychiatry 2003;53:

649-659.

3. Pies R. Are antidepressants effective in the acute

and long-term treatment of depression? Sic et non.

/moi/ Clin Neurosci. 2012;9:31 -40.

4. Kellner CH, Greenberg RM, Murrough JW, et al.

ECT in treatment-resistant depression. Am J Psy-

c/7/afry. 2012;169:1238-1244.

5. Mclntyre RS, Müller A, Mancini DA, Silver ES. What

to do if an initial antidepressant fails? Can Fam Phy-

sician. 2003:49:449-457.

6. Brown WA.Treatment response in melancholia.

Acta Psychiatr Scand Suppl. 2007;(433):125-129.

7. Trivedi RB, Nieuwsma JA, Wiiliams JW Jr. Exami-

nation of the utility of psychotherapy for patients with

treatment resistant depression: a systematic review.

J Gen intern Med. 2011 ;26:643-650.

8. Wiles N, Thomas L, Abel A, et al. Cognitive behav-

ioural therapy as an adjunct to pharmacottierapy for

primary care based patients with treatment resistant

depression: results of the CoBaiT randomised con-

trolled triai. Lancet. 2012 Dec 6; [Epub ahead of

print]. doi:10.1016/S0140-6736(12)61552-9. •

HIGHLIGHTS FROM www.PsychiatricTimes.œm

The Story of the Emergency Evacuation of

61 Psychiatric inpatients From Beiievue

Hospitai During Hurricane Sandy Four hospitals in New York City were evacu-

ated after Hurricane Sandy. Beiievue Hospi-

tal in Manhattan was one of those hospitals;

61 incarcerated psychiatric patients had to

be evacuated. In this podca.st, Elizabeth

Ford, MD, tells the story—an amazing ex-

perience of multiple systems, often at odds,

pulling together in a crisis.

www.psychiatrictimes.cotn/disaster-psychiatry

Psychiatric Probiems in Patients Who

Survive Critical iiiness Few psychiatrists know about the phenom-

ena involving delusional and hallucinatory

experiences of patients who survive critical

illnesses. Often patients come out of the

ICU with horrifying memories and don't

know what happened to them. Not only are

the patients debilitated by the physical ill-

ness, they are traumatized by the false mem-

ories resulting from delirium.

www.psychiatrictimes.com/mdd

Copyright of Psychiatric Times is the property of UBM Medica and its content may not be copied or emailed to

multiple sites or posted to a listserv without the copyright holder's express written permission. However, users

may print, download, or email articles for individual use.