LRP501

American Public University System

Abstract

This paper highlights eight peer-reviewed articles evaluating the role of Trazodone, a medication commonly prescribed for depression and insomnia, with a focus on the geriatric population and fall risk. An overview of Trazodone and its pharmacological properties and uses will be presented. A focus of the nature of pharmacology and the aging body will be presented, with a highlight of specific body systems that govern the internal function of medications, and how the aging body differs in the processing and elimination of these pharmacological compounds. Various risk factors associated with Trazodone and similar medications will be discussed in association to their level of fall risk. Alternative medications and naturally occurring compounds will be presented, as well as alternative treatment options that are exclusive of pharmacology. Suggestions for future research, as well as a proposed comprehensive model of care will be presented. Evaluations of the articles cited with limitations of the studies presented will be integrated into these suggestions of future research proposals.

Fall Risk and Trazodone in Aging Population

It has been noted in the medical community for some time that in aging populations special care and attention must be given to the medications prescribed to older patients. Due to their unique needs, a set of recommendations for prescribers has been established in the medical field. One of the most respected of these is known as the Beer’s Criteria, commonly referred to as the Beer’s List (Cauffield, 2007). This list, which is frequently updated, provides a list of medications that have been noted to increase risk factors for geriatric populations. It allocates risk based on high, medium, or low acuity, and cites the rationale for the risk factor. Two of the primary risk categories that are displayed in the Beer’s list are “Delirium” and “Falling” (Cauffield, 2007). Trazodone, has a history of being added to, and taken back off this list several times, the most current prescribing advise is to be prescribed with caution and increased monitoring (Roerig, 2001).

Also to be considered is the risk of polypharmacy in the elderly population. Jones (2006) found in a study of elderly patients, that many of them were taking multiple medications that had significant interactions, as well as taking several medications with overlapping indications which indicates polypharmacy or the use of several medications to treat one or more conditions. This leads to an increase in positive effects but it also increases the impact of side effects, which may be compounded when multiple medications with the same indication and the same side effects are taken to treat two different disorders or the same disorder. A complication of these positive effects is that it becomes difficult to determine which agent is causing a positive result, and which is causing a negative result, as well as the levels of each. Further it is recommended that patients who are prescribed psychotropic medications be titrated up and down when starting or discontinuing a psychotropic medication, this is not always performed, but has been found to be impactful in the reduction of initial side effects as well as withdrawal effects (Lloyd, 2011).

What is Trazodone?

Trazodone is a SARI (serotonin antagonist and reuptake inhibitor) class antidepressant medication (Roerig, 2001). It is noted at higher doses (300mg or more per day) for successful management of depression. It was initially created to help with pain management for major depressive disorder (MDD), under the ideology of the time that MDD had a significant lowering of the pain threshold, and therefore Trazodone could help with pain management via depression management (Roerig, 2001). It was noted by providers prescribing this medication at full depression management doses, that common side effects reported by patients such as excessive sedation, and confusion, that the medication was hard to tolerate throughout the course of the day (Roerig, 2001). These side effects were noted to decrease throughout the day. It was in this way that Trazodone came to be commonly prescribed before bed. It was also found that in lower doses, the side effects were less strong, as were the main effects. This led to Trazodone being prescribed at lower doses, (50mg-100mg) as a sleep aid (Roerig, 2001). At all doses, Trazodone has been noted to have some side effects, including sleepiness, dizziness, and nausea (Van Leuven, 2010). Of additional note is a special case involving Trazodone and priapism. One patient, who alleged that Trazodone caused a case of priapism so severe that it left him permanently impotent filed suit against the providing pharmacist for failure to provide appropriate cautionary information prior to taking the medication. In this case the patient won against the pharmacist, and this also led to an FDA regulation that there be a “black box” warning placed on the medication information given to every patient (Myhra, 2008). It is also noted on the patient education information for Trazodone that priapism, (a disorder noted by a lack of return of blood from a sexual organ within 4-6 hours) is a significant side effect of the medication, while rare; it has been noted to be very severe when it does occur (Roerig, 2001).

The Aging Body

As we age, our body changes, that much we are all familiar with from the external form and how it changes over time. The internal structure of the body undergoes major changes systemically and physically. Changes in the renal system decrease the body’s ability to excrete medications via a lowering of the level of function of the kidneys due to decrease mass and blood flow of the kidneys themselves, and a decrease in the enzymes they produce to assist the body with chemical transportation out of the body (Van Leuven, 2010). Similarly, decrease in function of the liver due to age may be as much as 30-40% (Van Leuven, 2010). Due to this more of the drug may be retained in the blood system for longer amounts of time than normal. Of critical note however is that this decrease in liver function will vary widely from patient to patient, and thus the recommendation for all medication titration is a personalized, monitored care plan created by the patients physician with knowledge of their present medical state, and history (Van Leuven, 2010). It may also be difficult for providers to obtain the correct dosage for most medications in the geriatric population. As the body ages, the ratio of fat and water content in tissues changes, which may increase or decrease a medications potency based on its ability to be dissolved into fat or water. This means that even for patients of an equivalent weight, the effective dosage for a medication may be dramatically different (Van Leuven, 2010). As these various factors start to add up and interact with one another it is easy to see how complex these scenarios can become. Consider a cardiac patient, who is taking HCTZ (hydrochlorothiazide), for hypertension and edema for congestive heart failure, the patient is also taking Trazodone which is water-soluble. The interaction between Trazodone and HCTZ could take two opposing sides, either the HCTZ will increase the rate of excretion for the Trazodone by increasing the ability to excrete the Trazodone, or the decrease in the volume of water in the body will concentrate the dosage of Trazodone to a much higher clinical level than original desired.

Risks

As proposed by Van Leuven, risks can be broken down into three primary categories: Intrinsic, extrinsic, and situational. Situational factors are those such as a need to rush to the bathroom in the middle of the night, or ambulation on uneven or icy surfaces. Extrinsic factors include dim lighting, lack of proper adaptive equipment such as handrails or grab bars, and obstruction of pathways. Intrinsic factors may include medical factors such as cardiovascular disease, loss of visual acuity, loss of hearing acuity, or medication side effects (Van Leuven, 2010). A review of medication studies performed by Sterke, Verhagen, van Beeck, and Tischa found evidence to support that the use of psychotropic medications provides for greater fall risk. Further, they found that the use of two or more psychotropic medications in the elderly population was of statistical significance in covariance with fall occurrence (2010). Van Leuven reports on the increase of fall risk mediated by Trazodone’s causational relationship with orthostatic hypotension (a decline in blood pressure when moving from a sitting or lying position to an upright position in a short period of time), cardiac disturbances, and blurred vision via anticholinergic effects (2010). Jones reports in a study of elderly patients, that 69% of the studied population were on multiple medications used to treat the same condition, with overlapping indications (2006). This increases the likelihood of side effects and increases confounding results for treatment by blurring the effects of individual medications and side effects. Taken together, it can be seen that the risk factors for falls and especially for falls resulting in injury (cited by Van Leuven as a leading cause of hospitalization and death for elderly patients, 2010), it can be concluded that the benefits of taking Trazodone as a treatment for insomnia or depression, may not outweigh the risks of taking it.

Alternatives

While longer-term medications such a psychotropic medications have been indicated for use in those who suffer from depression or chronic insomnia, alternative methods have been proposed. The use of behavioral therapy to identify psychological and behavioral barriers to successful sleep has been shown to have positive results for some patients (Roerig, 2001). Further the introduction of the pharmacist into the model of care has been suggested for the prevention of medication challenges by creating a tighter network between providers and prescribers to create more of a “safety net” for patients (Myhra, 2008). In this capacity, the pharmacist would be watchful for medications coming from multiple prescribers or providers that would indicate a case of polypharmacy, or an increase in risk of injury or fall. The pharmacist in this role would have a duty to initiate greater communication between providers who due to many reasons may not be aware of a patient’s entire medication regime or history. While it has been indicated in various legal cases that the pharmacist has a duty to warn patients of risks of medications and potential side effects, the increase of legal liability has led to most pharmacists substituting the medication packaging insert documentation (certified by the FDA), as opposed to a verbal consultation (Myhra, 2008).

Additional alternatives include over-the-counter remedies and herbal preparations that mimic the human body’s chemical signals for sleep. One such suggested supplement is Melatonin, which has been indicated for some patients to produce sufficient assistance with better quality of sleep that a stronger prescription medication was no longer necessary (Roerig, 2001). It has also been noted that for acute cases of insomnia a single dose of antihistamine such as diphenhydramine, may be enough to help a patient with a temporary decline in quality of sleep (Roerig, 2001).

Biopsychosocial Perspective

To create a biopsychosocial model for the treatment of depression and insomnia in elderly patients, one must look to the differences in perspectives of the patient and providers to create a unified model of care. Initially the patient must present with the disorder or condition, this would likely be to their primary care physician. The primary care physician should then analyze the patient’s current chart for cues for anything that may be causing the disturbance. The provider must consider life changes and events, such as loss of a loved one, or change in status, that would serve as an indication for the cause of the disturbance. The provider should then assess for need for a psychological referral for evaluation. This could be beneficial for cases where stress, major life events, or trauma would indicate that the patient would be better served with behavioral intervention. Alternative methods for relaxation and improved sleep hygiene would be good interventions at this level as well. Interventions may include yoga, meditation, decrease in activity level and light exposure, and avoiding stimuli which are known to cause arousal such as emotionally impactful television programming, or phone contact with a relative with whom there is much strife. Additional interventions to sleep hygiene may include reduction of use of bed for alternative behaviors such as reading or using a laptop, and creating a set sleep / wake schedule that is adhered to on weekends and weekdays. If this does not remedy the problem, then it could be indicated to try an acute trial of an antihistamine or an over the counter medication. Such trials are recommended to have a set date of termination and review (Sterke, et al., 2008). Following this an additional point of intervention could be a medication review and reconciliation followed by the introduction of a pharmacological agent such as a sedative, hypnotic, or antidepressant with these same qualities (such as Trazodone) with a set schedule for monitoring and interactions for all other medications being taken by the patient. In this model it would be imperative that the primary care provider, as well as all specialists have access to accurate patient histories and medication lists, and as a “safety net”, the pharmacist could be included to double-check for interactions with the current medication list, and support patient education as well as fielding questions within their realm of expertise. The pharmacist could also be critical in encouraging further interaction with providers by helping the patient to connect with these providers if the patient has a question that the pharmacist feels is out of their professional scope (Myhra, 2008). This model seeks to apply intervention in order of likelihood that the intervention may cause a negative impact on the individual in terms of fall risk or other negative side effect, with the least intensive intervention being behavioral modification and the most intensive being pharmacological.

Additionally, an educational program for providers, such as that reviewed by Lloyd, may be beneficial in calling more attention to the issue of fall risk in the elderly. Lloyd, discussed several interventions including in-service trainings, fall risk data collection for patient cases and the analysis of these incidents, to more collaboratively approach the fall risk in elderly patients (2011). This model can be expanded to individual providers reporting falls within their caseloads, as well as to facilities such as care facilities, hospitals, and even hospice settings to create a better tracking system for understanding which patients will be most at risk, and which interventions have been most successful in fall / injury prevention. It would be for the benefit of all geriatric patients if the expansion of this training included a training program for nurse practitioners and general care practitioners.

Discussion

One of the greatest challenges in concretely establishing an argument in support or opposition to the use of Trazodone in the elderly population is the mixed responses that it has received by the community. The medication has been added and subtracted from the Beer’s criteria numerous times, and because of this factor, as well as the fact that the Beer’s list is a recommendation and not a mandate, provider opinions of the medication have been very mixed (Cauffield, 2007). Also, while the Beer’s list is a commonly-used set of recommendations, there is no one unified body that captures the scope of regulation for prescribing medications in the geriatric population. As Cauffield notes, even the creators of the Beer’s list criteria themselves recommend that the guidelines not be taken as black-and-white standards, rather a set of guidelines backed by clinical observations that have been noted to occur with frequency (2007). It can also be argued that Trazodone is not as causative for fall risk as numerous other medications such as benzodiazepines which have been shown to have a number of much more severe side effects, that may become permanent in the elderly population (Roerig, 2001). Trazodone is frequently lumped in reference to other psychotropic medications and especially so in the subtype of antidepressant psychotropic medications, however Sterke found in an analysis of previous studies that while the use of an antidepressant increases fall risk with an 83% association rate, the specific role of Trazodone within that category was not determined in the scope of their study (2008). There have been many suggestions for increased monitoring and care for patients on psychotropic medications such as Trazodone, and the model suggested by Lloyd is beneficial to these patients by creating an increase in watchfulness for caregivers in facilities that care for the elderly. The limitation of this is that Lloyd’s work is not readily expanded out of the scope of a care facility or residential setting, and therefore may not be generalizable as a model for use in patients who reside within their own homes, and participate fully in their own self-care. Van Leuven’s work does have a lot of impactful suggestions for this population of individuals who have this level of independence, such as use of the Beer’s criteria, monitoring for polypharmacy and drug interactions, and screening for side effects whenever a provider is prescribing a psychotropic medication (2010). Additionally, Van Leuven highlights the changes in physiological condition that is noted with aging and makes recommendations for slower titration and capping the maximum dosage for elderly patients at 50% that of the standard adult dose. However, the shortcomings of this approach is that it does not integrate a more person-centered model, suggesting the role of behavioral health interventions nor does it recommend alternatives to treatment outside of the pharmacological realm.

A further challenge that has arisen as a complication in treatment of elderly patients is the role of the pharmacist. Once sought for advice and at one point even treatment, the role of the pharmacist has diminished with commercialization. This has been furthered by recent legal battles where medications have created harm to patients up and including death (Myhra, 2008). The role of the pharmacist has changed to being that of a more distant dispensary. This may be in part due to legal liability as the number of court cases debating the role of the pharmacist as having a “duty to warn” has led to lawsuits with massive financial ramifications (Myhra, 2008).

Future directions in research on this topic could include a more in depth study of Trazodone specifically in relation to its fall risk. Several of the listed studies examine Trazodone as well as other noted medications, which is beneficial for the comparison of traits examined but it does not allow for more in-depth studying of the effect of Trazodone on the geriatric population. Further studies may examine this population exclusively with clinical trials and case analyses to determine the impact of Trazodone on fall risk in this population. Alternatively, trials involving the use of Trazodone as compared to other medications such as Nefazodone may help to unlock further clues into the likeliness of experiencing side effects that increase the risk of falls when taking medications of this type (Roerig, 2001). Nefazodone is a medication, which is similar in chemical structure and pharmacological action as Trazodone, and has not been noted to have the same risks of sexual dysfunction, or other side effects increasing side effects. It has however been noted to have several other side effects such as vision disturbances which may indicate that it is not in fact a better option. This medication has been studied much less than Trazodone and further research into the development of new treatments may gain benefit from studying further the treatments already in place.

Alternative preparations such as Valerian may also benefit from further study. Valerian is a naturally occurring herb and has been noted throughout history for possessing pharmacological properties (Roerig, 2001). Studies have found that it has been more effective than placebo in extended trials and there have been very few reports of side effects from taking Valerian (Roerig 2001). However, the effects of this substance have been found to be significantly less potent than manufactured pharmaceuticals, and this substance has also been noted to not be of much impact in small doses or single doses. Further studies of this medication as well as a focus on how the active compounds of this substance functions (which are not fully understood), may unlock more keys into finding a treatment for insomnia that have fewer side effects, and have more effect with less chemical intervention necessary.

Further examination into the role of the pharmacist as an advisor may be warranted to create legal boundaries and social boundaries beneficial to providers and patients. The current legal status of a pharmacist’s role in patient education has been primarily circumvented by FDA regulation. While this creates a more reliable and consistent patient education system, it undermines the role of the pharmacist as being a keystone of patient support and education due to the fear of legal liability. Going back 50 years the pharmacist’s role was that of a counselor and even recommending treatment options to patients directly from that role. In current times it is observed that the pharmacist is primarily seen as a dispensing agent only, with the liability to reliably and consistently translate and provide accurate manifestations of the prescribers orders, and not to otherwise present opinions on them. Further research may focus on the integration of the pharmacist into a comprehensive model of care acting as an agent between patient and doctors to provide their perspective and expertise, and establishment of the legal role of the pharmacist with appropriate boundaries and expectations is critical to this integration.

Future studies may also examine the role of health insurance providers as a means of intervention for the management of patients in the aging population. Current trends include the integration of HEDIS measures which seek to evaluate the quality of care and monitoring of biometric information for providers of managed care health plans (Jones, 2006). HEDIS (Healthcare Effectiveness Data and Information Set), was introduced by the NCQA (National Committee for Quality Assurance) in 2010 as part of an initiative to evaluate and quantify the quality of services provided by managed care health plans (NCQA, 2011). These measures seek to compare healthcare plans based on the number of hospitalizations experienced by patients under care management and thereby seek to provide intervention, prevention and education to managed care patients to assist in the avoidance of fall incidents. This is similar to the Beer’s list as it is a standard created by its own audience, and thus is not a mandated measure despite common use. As the role of social or federal healthcare systems begins to take shape, the evaluation of the Beer’s criteria as well as the HEDIS measures model may be beneficial to create a unified standard of measurement, and evaluation. This could create new models for patient education and help further with fall risk. In doing so the role of Trazodone and similar medications would need to be further scrutinized as it has attained a variable status for recommendation or avoidance through its time on the market (Roerig, 2001).

References