Psychotropic Medications

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

QI Domains And Psychoactive Medications Skin Care Accidents Quality of Life Behavioral/Emotional Problems QI Domains Psychotropic Drug Use Clinical Management Physical/ Functioning Cognitive Patterns Elimination/ Incontinence Nutrition/Eating Infection Control

Paradigm for Comprehensive Assessment Cognitive enhancers • Dementia • Frontal lobe impairment • Delirium • Medical illness • Psychotic disorder • Affective disorder • Anxiety disorder • Personality disorder • Environment/stressors Mood Stabilizers Antipsychotics Antidepressants Anxiolytics

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 Treatment goal is to titrate to the highest dose tolerated

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

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 Slide courtesy of: Schneider L. Geriatrics. 2003(Aug);Suppl

MemantineStudy 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

Antipsychotics Conventionals Atypicals Risperidone Olanzapine Quetiapine Ziprasidone Aripiprazole Mood stabilizers Carbamazepine Divalproex sodium Lithium Topiramate Gabepentin Benzodiazepines Frontal Lobe Impairment: Pharmacologic Management

Mood Stabilizers • 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: carbamazepine (Tegretol) divalproex sodium (Depakote)gabapentin (Neurontin)lithium (Lithium)topiramate (Topimax)

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

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 1. Tariot et al, 2000

Divalproex in Elderly Mania / Dementia Cohen-Mansfield Agitation Inventory (Total Scores) * Mean Change from Baseline * * * * (SE=2.72) (SE=2.65) 7 14 35 42 0 21 28 Days *p<0.05 for group differences Tariot et al, 2001

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 µg/ml • Clinical response more important than serum level

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 Stoudemire A. Gen Hosp Psych. 1996;18:77-94 The Long Term Care Survey.ACHA

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 Accepted Diagnosis for Antipsychotic Use in LTC

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

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

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

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

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)

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

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 1. Web site address http://www.hc-sc.gc.ca/hpb-dgps/therapeut/zfiles/english/advisory/industry/risperdal

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.

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…?

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

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 Insomnia can be effectively treated with the addition of Trazodone, Ambien, or Sonata

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

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)

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 Anxiolytic

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

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

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.

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

Remember, Psychotherapy Can Also Help Some Residents

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.

Psychotropic Medications