Psychotropic Medications

1. 1 Psychotropic Medications Broad term encompassing any medication used to influence mood, mental status or behavior CMS guidelines break them into four categories: Anti-psychotics Anti-anxiety agents Hypnotics Antidepressants Additional important categories Cognitive enhancers Mood stabilizers

2. 2 QI Domains And Psychoactive Medications

3. 3 Paradigm for Comprehensive Assessment Dementia Frontal lobe impairment Delirium Medical illness Psychotic disorder Affective disorder Anxiety disorder Personality disorder Environment/stressors

4. 4 Acetylcholinesterase Inhibitors (AChI) Aricept (donepezil) Start: 5 mg qhs x 4 � 6 wks, then Increase to 10 mg qhs Exelon (rivastigmine) Start: 1.5 mg bid w/ meals x 2 - 4 wks Target dose 6 mg bid, titrate 1.5 mg q 2 - 4 weeks Reminyl (galantamine) Start 4 mg bid Target dose is 24 mg qd Titrate by 4 mg bid increase q 4 weeks

5. 5 ACHI Treatment Effects Initial improvement may be seen @ 2 - 4 weeks At 26 wks: Approximately 20% of mild/mod pts will have significant cognitive improvement Approximately 80% will remain above baseline for function for 6-10 months Cost vs benefit analysis ongoing Watch for significant sudden decline when stopped Initial data indicates delay in NH placement >20 months in those with 4 years of donepezil use

6. 6 Memantine Marketed in Germany since 1982 for �Organic Brain Syndrome� and spasticity Approved as Namenda in October 2003 for �moderate to severe� Alzheimer�s Disease No significant food interaction, i.e., can be administered without regard to meals Interactions with highly protein-bound drugs unlikely No interactions with acetylcholinesterase inhibitors

7. 7 Memantine Study Results Memantine treatment was associated with less decline vs. placebo on: Global, CIBIC-plus Cognition, Severe Impairment Battery Function, ADCS-ADL outcome measures Patients switched from placebo to Memantine showed significant improvement relative to projected decline Memantine treatment resulted in reductions in caregiver time, institutionalisation rate and total costs compared to the placebo group Memantine was well-tolerated with dropout rates and side effects rates similar or lower than placebo

8. 8 Paradigm for Comprehensive Assessment Dementia Frontal lobe impairment Delirium Medical illness Psychotic disorder Affective disorder Anxiety disorder Personality disorder Environment/stressors

9. 9 Frontal Lobe Impairment: Pharmacologic Management Antipsychotics Conventionals Atypicals Risperidone Olanzapine Quetiapine Ziprasidone Aripiprazole Mood stabilizers Carbamazepine Divalproex sodium Lithium Topiramate Gabepentin Benzodiazepines There are 3 classes of medications that have been used for the treatment of frontal lobe disinhibition. These include antipsychotics, mood stabilizers, and benzodiazepines. Very little data is available for most of these medications and the treatment of frontal symptoms per se. The following slides will focus on Carbamazepine and Divalproex as the most commonly used and best studied. Additional information regarding antipsychotics will be given in the section on treatment of psychotic disorders. There are 3 classes of medications that have been used for the treatment of frontal lobe disinhibition. These include antipsychotics, mood stabilizers, and benzodiazepines. Very little data is available for most of these medications and the treatment of frontal symptoms per se. The following slides will focus on Carbamazepine and Divalproex as the most commonly used and best studied. Additional information regarding antipsychotics will be given in the section on treatment of psychotic disorders.

10. 10 These pathways transmit gamma-aminobutyric acid (GABA). Lower levels of GABA associated with aggressive animal behavior. NH study of 56 agitated elderly patients given Carbamazepine had significant improvement in agitation and decreased staff time needed. Newer anticonvulsants advantageous due to improved side effect profile but have few good clinical studies Mood Stabilizers

11. 11 Mood Stabilizers:

12. 12 Mood Stabilizers Their role is uncertain at present No need to monitor serum/blood levels for Lamictal or Topimax Behavior effects can be seen at low serum levels The role of multiple mood stabilizers concurrently remains uncertain Documentation on the working diagnosis and monitoring of benefits and side effects remains important

13. 13 Divalproex Study in Dementia Randomized, double-blind, placebo-controlled trial1 N=172 NH residents met criteria for secondary mania Target dose 20 mg/kg/day in 10 days N=100 completers Statistically significant improvement on CMAI score Consistent with antiagitation, not antimanic effects Study suspended due to side effects (sedation) Follow-up indicated with lower doses/slower titration The next major mood stabilizer investigated was Depakote. Additional small studies highlighted the positive effects of Divalproex in similar demented, agitated, disinhibited patients. A large (N = 172) multi-centered double-bind placebo trial was undertaken. Unfortunately, the goal of 20 mg/kg in this frail elderly population was too much too soon. While the study found that the patients who were able to titrate the Divalproex dose showed improvements in symptoms, the study was suspended because of the high incidence of sedation. The next major mood stabilizer investigated was Depakote. Additional small studies highlighted the positive effects of Divalproex in similar demented, agitated, disinhibited patients. A large (N = 172) multi-centered double-bind placebo trial was undertaken. Unfortunately, the goal of 20 mg/kg in this frail elderly population was too much too soon. While the study found that the patients who were able to titrate the Divalproex dose showed improvements in symptoms, the study was suspended because of the high incidence of sedation.

14. 14 Divalproex in Elderly Mania / Dementia This slide shows the results from the double blind Depakote study. Using the Cohen-Mansfield Agitation Inventory as the primary outcome measure, patients on active medication showed a significant improvement in symptoms in as quickly as 14 days. The statistically significant benefit was seen throughout the study. A large number of patients on active medication were withdrawn from the study secondary to sedation and daytime lethargy. This study has been reactivated using lower total doses and a slower dose titration. This slide shows the results from the double blind Depakote study. Using the Cohen-Mansfield Agitation Inventory as the primary outcome measure, patients on active medication showed a significant improvement in symptoms in as quickly as 14 days. The statistically significant benefit was seen throughout the study. A large number of patients on active medication were withdrawn from the study secondary to sedation and daytime lethargy. This study has been reactivated using lower total doses and a slower dose titration.

15. 15 Valproate Summary Clinical effects similar to Carbamazepine � risk of drug interaction � SE profile More definitive controlled trial underway Current clinically recommendations Initial dose 125-250 mg bid with � 125-250 q 5d Usual range 500 - 1,250 mg/d Usual level 40-90 �g/ml Clinical response more important than serum level In summary, while lacking a completed randomized double-blind placebo controlled multi-centered trial, Divalproex has shown benefits in dementia patients with aggression, agitation and disinhibition. The risk of serious side effects is low. Regular monitoring (q 6 months) of platelet counts and liver function may be prudent. Starting doses are 125-250mg bid with dose titration every 3-5 days until desired clinical effects are noted or side effects emerge. In summary, while lacking a completed randomized double-blind placebo controlled multi-centered trial, Divalproex has shown benefits in dementia patients with aggression, agitation and disinhibition. The risk of serious side effects is low. Regular monitoring (q 6 months) of platelet counts and liver function may be prudent. Starting doses are 125-250mg bid with dose titration every 3-5 days until desired clinical effects are noted or side effects emerge.

16. 16 Paradigm for Comprehensive Assessment Dementia Frontal lobe impairment Delirium Medical illness Psychotic disorder Affective disorder Anxiety disorder Personality disorder Environment/stressors

17. 17 OBRA Guidelines: Antipsychotics Use only if patients exhibit symptoms that impair functioning or cause danger to themselves or others, and/or interfere with provision of care Agitated behavior is an insufficient reason to use an antipsychotic medication (i.e. must be psychotic or aggressive) Considered unnecessary if initiated as treatment in the absence of documentation of the approved indications Use requires approved diagnosis and symptoms These OBRA guidelines come straight from the Long Term Care Survey which is used as the handbook to surveyors. This document outlines the approved indications for antipsychotic use. The most critical issue is that the documentation MUST substantiate the need for these medications. Within the Long Term Care Survey Guidance to Surveyors Handbook it is written, �It is important to note that these regulations and interpretive guidelines are not meant to cast a negative light on the use of psychopharmacological drugs in long-term car facilities�. It is however, easy to understand why surveyors focus on the issues surrounding appropriate use of antipsychotics as there is a history of overuse in the LTC setting. The goal of the regulations is also to prevent the use of psychopharmacological drugs when behavioral symptoms are caused by conditions such as environmental stressors (e.g. noise, crowding) psychosocial stressors(e.g. abuse, taunting) or treatable medical conditions. These OBRA guidelines come straight from the Long Term Care Survey which is used as the handbook to surveyors. This document outlines the approved indications for antipsychotic use. The most critical issue is that the documentation MUST substantiate the need for these medications. Within the Long Term Care Survey Guidance to Surveyors Handbook it is written, �It is important to note that these regulations and interpretive guidelines are not meant to cast a negative light on the use of psychopharmacological drugs in long-term car facilities�. It is however, easy to understand why surveyors focus on the issues surrounding appropriate use of antipsychotics as there is a history of overuse in the LTC setting. The goal of the regulations is also to prevent the use of psychopharmacological drugs when behavioral symptoms are caused by conditions such as environmental stressors (e.g. noise, crowding) psychosocial stressors(e.g. abuse, taunting) or treatable medical conditions.

18. 18 Accepted Diagnosis for Antipsychotic Use in LTC Schizophrenia Schizo-affective Disorder Delusional Disorder Psychotic Mood Disorder Acute Psychotic Episodes Brief Reactive Psychosis Schizophreniform Disorder Atypical Psychosis Tourettes Disorder Huntington�s Disease 11. Organic Mental Syndromes IF certain criteria are met The OBRA guidelines require an �approved� diagnosis to allow the use of antipsychotics in LTC residents. All of the chronic psychotic mental disorders are allowed as listed above. Organic mental disorders are also acceptable if additional symptom, function and documentation criteria are met. The following slide delineates the required elements of organic mental syndromes allowing use of antipsychotics as well as when they may not be used. The OBRA guidelines require an �approved� diagnosis to allow the use of antipsychotics in LTC residents. All of the chronic psychotic mental disorders are allowed as listed above. Organic mental disorders are also acceptable if additional symptom, function and documentation criteria are met. The following slide delineates the required elements of organic mental syndromes allowing use of antipsychotics as well as when they may not be used.

19. 19 Treatment with Antipsychotics Requires: Quantitative and Objective Documentation that: The behavior requires intervention You determined if the behavior is permanent or transitory The behavior has been evaluated for possible social or situational causes Environmental causes have been ruled out Medical causes have been ruled out The symptoms are persistant Not caused by preventable reasons The details of the symptoms and assessment that must be documented to justify treatment with antipsychotics are listed in the next two slides. There is the requirement that the behaviors and the assessment must be quantified and documented. This is an important element as behavior charting is notoriously poor, often even absent or filled with zeros, although significant problems may exist. The details of the symptoms and assessment that must be documented to justify treatment with antipsychotics are listed in the next two slides. There is the requirement that the behaviors and the assessment must be quantified and documented. This is an important element as behavior charting is notoriously poor, often even absent or filled with zeros, although significant problems may exist.

20. 20 Treatment with Antipsychotics Requires: Organic Mental Syndromes with associated psychotic and/or agitated behaviors defined by: Specific Behaviors (biting, kicking, extreme fear, etc) that have been quantified AND present a danger to themselves or others (including staff) Continuous crying out, screaming or pacing if quantified and cause a functional impairment or actually interfere with the staff�s ability to provide care Psychotic symptoms (AH, VH, PI, delusions) that are not dangerous but cause distress or an impairment in functional capacity The final features required to use antipsychotics are listed on this slide. The critical feature is that the behavior must either be dangerous, cause patient distress, or impair the delivery of care. The final features required to use antipsychotics are listed on this slide. The critical feature is that the behavior must either be dangerous, cause patient distress, or impair the delivery of care.

21. 21 Antipsychotics Should NOT be used if: the following symptoms are the ONLY criteria Wandering Poor self-care Anxiety/Restlessness Impaired memory Uncomplicated Depression Unsociability Fidgeting Nervousness Uncooperativeness Agitation without any danger to resident or others It is critical to understand what kinds of symptoms do not justify treatment with antipsychotics according to the regulations. The regulations include this detailed list of �not allowed symptoms� as shown above. The regulations are quite clear that the �not allowed symptoms� are never sufficient as a sole criteria for treating with antipsychotics. It is critical to understand what kinds of symptoms do not justify treatment with antipsychotics according to the regulations. The regulations include this detailed list of �not allowed symptoms� as shown above. The regulations are quite clear that the �not allowed symptoms� are never sufficient as a sole criteria for treating with antipsychotics.

22. 22 Antipsychotic Medication Guidelines F-tag 330: Use only as necessary to treat a specific condition as diagnosed & documented in the clinical record F-tag 331: Gradual dose reductions & behavioral interventions, unless clinically contraindicated, are required in an effort to discontinue these drugs Currently, only IM Zyprexa is approved by the FDA for the treatment of acute agitation in dementia Usually reserved for dangerous or very distressed psychotic symptoms such as aggression, delusions or hallucinations

23. 23 Antipsychotic Medication Guidelines The cause of the psychosis indicates the treatment duration: For psychosis as a symptom of dementia, stabilizing behavior may take as long as 12 weeks and may require treatment for at least several months and up to a year For Schizophrenia, antipsychotic treatment is lifelong although the dose may decrease with age For Bipolar illness, antipsychotics are used during acute mania or long term to prevent relapse For psychotic depression, antipsychotics are typically needed for a few months in addition to a longer term antidepressant For delirium, antipsychotics are needed for a few days to a few weeks (even after medical problem is cleared)

24. 24 Antipsychotics �Typicals� Haldol (haloperidol ) Thorazine (chlorpromazine) Many others �Atypicals� Clozaril (clozapine) Risperdal (risperidone) Zyprexa/Zydis (olanzapine) Seroquel (quetiapine) Geodon (ziprasidone) Abilify (aripiprazole)

25. 25 Atypical Antipsychotics and Increased Stroke Risk Data from four International studies revealed increased incidence of CVA & TIA in Risperidone treated pts 1 In 2003, the FDA changed the Risperdal label warning that the use of Risperidone dementia patients has an increased risk of stroke Currently a similar label is pending for Zyprexa Perhaps increased stroke risk is a �class effect� Stroke risk should be included in the risk/benefit assessment The first two bullets describe the Canadian response to four different international studies, each of which noted an increased risk of CVA in the study population. This does not imply causation, and more studies are needed to see if this is a sporadic result. There have been other international studies that do not corroborate this finding. The first two bullets describe the Canadian response to four different international studies, each of which noted an increased risk of CVA in the study population. This does not imply causation, and more studies are needed to see if this is a sporadic result. There have been other international studies that do not corroborate this finding.

26. 26 Antipsychotics: Summary Atypicals are effective in the management of psychosis in the elderly In elders, atypicals offer improved safety and tolerability compared with conventional agents Differences in tolerability/side effect profiles between atypicals impact treatment selection It is critical to evaluate for Parkinson�s symptoms before choosing the atypical to avoid worsening motor symptoms. We have shown considerable data regarding the negative outcomes in the elderly when conventional antipsychotics are used. Additionally, atypicals have at least as good efficacy with a far superior side effect profile, especially regarding EPS. When we are treating patients with increased risk factors for Parkinsonism, special care should be used when choosing the atypical agent as even these can impact motor disturbances. We have shown considerable data regarding the negative outcomes in the elderly when conventional antipsychotics are used. Additionally, atypicals have at least as good efficacy with a far superior side effect profile, especially regarding EPS. When we are treating patients with increased risk factors for Parkinsonism, special care should be used when choosing the atypical agent as even these can impact motor disturbances.

27. 27 Paradigm for Comprehensive Assessment Dementia Frontal lobe impairment Delirium Medical illness Psychotic disorder Affective disorder Anxiety disorder Personality disorder Environment/stressors

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29. 29 Treatment of Major Depression There is no �good reason� for depression to ever go untreated Start low, go slow, but go! Strive for maximum recovery/function Compare GDS or Cornell Treat the sleep disturbance initially then change to a prn after 2-3 wks The dose that gets them well, keeps them well Continue for 6-12 months or perhaps even lifelong�? This slide summarizes some of the main clinical concerns when assessing and treating depression in the elderly. It is very important that while generally low doses are used initially (for all antidepressants except Mirtazapine) it is important to raise the dose until it is in the therapeutic range. Typically, this means raising the dose to midrange for 6 � 10 wks, and then depending on clinical response, consider raising the dose to full therapeutic level for geriatric patients. It is extremely useful to repeat the GDS 15 or Cornell to monitor treatment effects. There is no evidence that decreasing the dose before titrating the patient off the medication is of any benefit. Of course, dose reduction may be needed to manage side effects. The issue of when to titrate the patient off the antidepressant is quite clear for younger patients but less so, even controversial when considering the elderly. For geriatric patients, you are always considering any single medication use or discontinuation in the context of the whole person. If for example, the person was in their 90�s, had a very severe depressive episode requiring hospitalization, then responded extremely well without side effect problems to treatment, many would argue that the risks of relapse outweighs the polypharmacy risk of continuing the medication. In this population, no medication or treatment should be considered in isolation. This slide summarizes some of the main clinical concerns when assessing and treating depression in the elderly. It is very important that while generally low doses are used initially (for all antidepressants except Mirtazapine) it is important to raise the dose until it is in the therapeutic range. Typically, this means raising the dose to midrange for 6 � 10 wks, and then depending on clinical response, consider raising the dose to full therapeutic level for geriatric patients. It is extremely useful to repeat the GDS 15 or Cornell to monitor treatment effects. There is no evidence that decreasing the dose before titrating the patient off the medication is of any benefit. Of course, dose reduction may be needed to manage side effects. The issue of when to titrate the patient off the antidepressant is quite clear for younger patients but less so, even controversial when considering the elderly. For geriatric patients, you are always considering any single medication use or discontinuation in the context of the whole person. If for example, the person was in their 90�s, had a very severe depressive episode requiring hospitalization, then responded extremely well without side effect problems to treatment, many would argue that the risks of relapse outweighs the polypharmacy risk of continuing the medication. In this population, no medication or treatment should be considered in isolation.

30. 30 Common Antidepressants SSRI�s Fluoxetine (Prozac) Paroxetine (Paxil) Sertraline (Zoloft) Citalopram (Celexa) Escitalopram (Lexipro) SNRI�s Bupropion (Wellbutrin) Mirtazapine (Remeron) Venlafaxine (Effexor) Trazodone (Desyrel) too sedating to treat depression

31. 31 Depression Therapy TCA�s vs. SSRI�s vs. SNRI�s Select the drug based on target symptoms and the side effects wanted, for example Dep. + anorexia � mirtazapine Dep. + lethargy � activating antidepressant Dep. + constipation � sertraline Dep. + psychosis - cymbiax

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33. 33 Paradigm for Comprehensive Assessment Dementia Frontal lobe impairment Delirium Medical illness Psychotic disorder Affective disorder Anxiety disorder Personality disorder Environment/stressors

34. 34 Anxiolytic Therapy Guidelines F-tag 329: Guidance to Surveyors Short-acting & maximum doses indicated Behavioral monitoring charts needed Does not indicate how to monitor Gradual dose reduction al least twice within one year before can conclude dose reduction is clinically contraindicated per regulations

35. 35 Anxiolytic Therapy Guidelines Indications for use: - other reasons for the distress have been considered & eliminated - use results in maintenance/improvement of resident�s functional status - reduction must be attempted by 4 months - specific diagnoses (anxiety disorder, organic mental syndromes, panic disorder, anxiety in concert with another psychiatric disorders)

36. 36 lorazepam (Ativan) 0.25 � 2.0 mg /d alprazolam (Xanax) 0.25 � 1.5 mg / d oxazepam (Serax) 7.5 � 30 mg / d buspirone (BuSpar) 10 � 45 mg / d temazepam (Serax)klonzepam (Klonopin) 0.25 -3.0 mg / d

37. 37 Benzodiazepines Minimal efficacy data Sedating Further inhibit learning and memory Ataxic gait is episodic - difficult to assess Associated with falls Paradoxical disinhibition possible Avoid long acting benzodiazepines in the elderly Benzodiazepines, while often effective in treating either the symptom of anxiety or an anxiety disorder, do carry a substantial risk of adverse events as well as developing tolerance. Such side effects include worsening confusion, sedation and ataxia with falls. Of great concern is that the ataxia can be episodic. A clinician evaluating the patient can find their gate stable giving a false sense of security. Benzodiazepines, while often effective in treating either the symptom of anxiety or an anxiety disorder, do carry a substantial risk of adverse events as well as developing tolerance. Such side effects include worsening confusion, sedation and ataxia with falls. Of great concern is that the ataxia can be episodic. A clinician evaluating the patient can find their gate stable giving a false sense of security.

38. 38 Anxiety Disorder: Treatment Short-acting benzodiazepines sedating, inhibit learning, increases fall risk Trazodone check orthostatic BP and Pulse Buspirone? If paranoid or psychotic component, consider Atypicals Consider antidepressants, may need empiric trial

39. 39 Insomnia - Hypnotics F-tag 329: Unnecessary drugs: GTS Address �sleep hygiene� issues Daily dose 10 or more continuous days requires documentation of necessity for maintenance or improvement of functional status. Maximum hypnotic dosages Dose reduction attempts at least 3 times within 6 mo. before declaring further reductions are contraindicated.

40. 40 Insomnia � Hypnotics - 2 Trazodone 25-200 mg @hs Mirtazepine (Remeron) 7.5-45 mg @hs Short-acting benzodiazepine Zolpidem (Ambien) 5-10 mg @hs Zalepion (Sonata) 5-10 mg @hs Melatonin 3 mg @ 6 pm

42. 42 Summary Distressed behaviors are only symptoms Unless urgent, a complete assessment to determine/develop a working diagnoses should guide the long term treatment approach. Consider nonpharmacologic management in every case. Monitor treatment benefits: MMSE, GDS, FAST, Cornell dementia in depression scale, Behave AD, Cohen Mansfield Agitation Inventory Optimal care requires teamwork, education, and respect. This purpose of this review has been to highlight the need to view distressed behaviors as symptoms that are being caused by something. The possible causative factors are not only numerous but may also occur concomitantly. Our job becomes finding the multifactorial etiologies in the bio-psycho-social areas. We need to exam the patients for inappropriate or sub-optimal environment, as well as underlying neurological, medical, and psychiatric diagnosis. The careful and thorough evaluation by using the nine part assessment allows us to be sure we find all of the issues that warrant further attention. The premise of this discussion is that when behavior is seen as �distressed� we should keep the differential diagnosis as wide as possible until the complete evaluation is completed. An evaluation is complete only after all nine areas have been considered. During this process it is common to find several areas worthy of intervention. It is our intention with this model to assess and treat all the concomitant factors involved in the patients� presentation that have contributed to the distressed or disturbed behavior. The life of every resident in a LTC facility can be improved with thoughtful nonpharmacological interventions. We as clinicians need to lead the team in considering this often neglected but powerful approach. This purpose of this review has been to highlight the need to view distressed behaviors as symptoms that are being caused by something. The possible causative factors are not only numerous but may also occur concomitantly. Our job becomes finding the multifactorial etiologies in the bio-psycho-social areas. We need to exam the patients for inappropriate or sub-optimal environment, as well as underlying neurological, medical, and psychiatric diagnosis. The careful and thorough evaluation by using the nine part assessment allows us to be sure we find all of the issues that warrant further attention. The premise of this discussion is that when behavior is seen as �distressed� we should keep the differential diagnosis as wide as possible until the complete evaluation is completed. An evaluation is complete only after all nine areas have been considered. During this process it is common to find several areas worthy of intervention. It is our intention with this model to assess and treat all the concomitant factors involved in the patients� presentation that have contributed to the distressed or disturbed behavior. The life of every resident in a LTC facility can be improved with thoughtful nonpharmacological interventions. We as clinicians need to lead the team in considering this often neglected but powerful approach.