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Pharmacologic Interventions in the Management in Behavioral Problems in Dementia

Bruce Gerlich, R.Ph . Consultant Pharmacist Omnicare 12 March 2013. Pharmacologic Interventions in the Management in Behavioral Problems in Dementia. Disclosure. Bruce Gerlich has no financially relevant relationships with any commercial entity pertaining to this activity. Objectives .

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Pharmacologic Interventions in the Management in Behavioral Problems in Dementia

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  1. Bruce Gerlich, R.Ph. Consultant Pharmacist Omnicare 12 March 2013 Pharmacologic Interventions in the Management in Behavioral Problems in Dementia

  2. Disclosure • Bruce Gerlich has no financially relevant relationships with any commercial entity pertaining to this activity

  3. Objectives • Describe risks and benefits of psychoactive medication use in elderly with dementia • Understand the limits of benefit of pharmacologic tx in this population

  4. Algorithm for Drug Therapy of Behavior Problems in Senile Dementia ACHEIs ± memantine Depression Agitation/ Aggression psychosis Atypical antipsychotics SSRI antidepressants trazodone SSRI Antidepressants Carbamazepine Valproic acid If monotherapy fails use combination tx judiciously Atypical antipsychotics Clinical Geriatrics 2011 19(6); 31-2; 34-40

  5. When to Initiate Drug Therapy BPSD pose a danger to the patient or caregiver or cause… • Subjective distress • Impairment in function • Interference with care • Balance of benefits and risks • Specific symptoms likely to respond to drug therapy • American Association for Geriatric Psychiatry, position statement, 2006

  6. General Principles of Drug Therapy • Target specific symptoms • Set goals of therapy • Start low and go slow • Attempt to withdraw medication at regular intervals • Remember that response can be unpredictable

  7. “Normal” Behaviors Associated with Degenerative Dementias Generally Unresponsive to Psychoactive Medications • Wandering* • Disrobing • Persistent disruptive vocalization (swearing, offensive comments, yelling/screaming)* • Restlessness/repeated attempts to unsafely arise from chair or climb out of bed* • Inappropriate urination/defecation • Hiding/hoarding • Eating inedibles • Annoying repetitive activities, including “exit seeking” • Climbing into bed with other residents • Sleep disturbance, diurnal reversal* • Pushing wheelchair-bound residents • * may be related to pain or discomfort

  8. Dementia drugs for Non-cognitive sx • Early use may prevent of delay behavioral sx • Behavioral outcomes typically secondary, post-hoc analysis • Target sx vary • Acetylcholinesterase • Inhibitors (AChEIs) • • Mood (depression, anxiety) • Apathy Memantine • Irritability •Agitation/Aggression • 2005;293(5):596-608 • Alzheimers Dement. 2008;4(1):49-60 • J Clin Psychiatry. 2008;69(3):341-8 • Curr Psychiatry Rep. 2012;14(4):298-309

  9. Depression – Consensus? *Guidelines recommend ECT in cases of refractory depression AAN –American Academy of Neurology AGS- American Geriatric Society CCSMH –Canadian Coalition for Seniors Mental Health

  10. Mood Stabilizers for Agitation/Aggression

  11. Agitation/Aggression – Consensus? Aging Res Rev 2012 11(1) 78-80

  12. THE HEADLINES • Mortality Risk in Elderly Dementia Patients May Rise With Newer Antipsychotics • Antipsychotics Increase Risk for Stroke in Elders • Psych Drugs Linked to MI Risk in Dementia • Again, Higher Mortality with Antipsychotics in Patients with Dementia • Rapid Serious Adverse Events with Antipsychotics in Dementia • Antipsychotics Linked to Increased Risk for Hyperglycemia in Older Patients with Diabetes • Antipsychotics Increase Risks for Sudden Cardiac Death

  13. Pathophysiology of BPSD The causes of BPSD are unclear; however changes in behavior may be caused by biological, psychological, or environmental factors - Biological › disruption in neurochemical mechanisms may be underlying cause of BPSD; ↑ dopaminergic neurotransmission; altered serotonergic modulation of dopaminergic transmission > Use of antipsychotics to target these pathways Front Neurol 2012:3:73 (Epub 2012 May 7) NeurochemInt 2008 May;52(6):1052-60

  14. Conventional AntipsychoticsEfficacy Since their approval for Schizophrenia in the 1950s, conventional antipsychotics have been used to treat BPSD despite lack of evidence - Agent of choice - Haloperidol has been the agent of choice among the conventional antipsychotics given its affinity for D2 receptor and clinician experience - Early trials using Haloperidol observed only a modest improvement when tx BPSD when compared to placebo J Am Geriatric Soc. 1990; 38(5); 553-563

  15. Adverse Drug ReactionsConventional Antipsychotics • Sedation • Anticholinergic Activity • Prolactin elevation • Sexual Dysfunction • ExtrapyramidalSx (EPS) • Pseudoparkinsonism -Akathesia • Acute dystonia - Tardivedyskinesia Br J Psychiatry 2010; 196(6); 434-439

  16. Atypical Antipsycoticsefficacy *average dose AD-alzheimer disease VaD-vascular dementia mixed-mixed dementia CurrNeuropharmacol. 2008 6(2) 117-24

  17. Atypical Antipsychoticsefficacy *Average dose CurrNeuropharmacol 2008:6(2); 117-24

  18. Effectiveness in Dementia • Antipsychotic effect takes 3-7 days to start working • Very sedating medication - acute effect is most likely due to sedating effect not antipsychotic effect • In RCTs, recipients do a little bit better than placebo but the effect beyond 3 months is unclear • Not everyone who receives the meds improve • A large number of people getting the placebo improve • The net effect is that 10 to 20 people out of 100 who receive the medication improve due to the medication

  19. Adverse Drug ReactionsAtypical Antipsychotics • Weight gain – risk of diabetes • QTc prolongation • Tardivedyskinesia • Extrapyamidal Symptoms • Orthostatic hypotension • BLACK BOX WARNING Br J Psychiatry 2010; 196(6); 434-9

  20. FDA Black Box Warning

  21. Net effectiveness • “For every 100 patients with dementia treated with an antipsychotic medication, only 9 to 25 will benefit and 1 will die” • Drs Avorn, Choudhry & Fishcher, Harvard Medical School • Dr Scheurer, Medical University of South Carolina Source: Independent Drug Information Service (IDIS) Restrained Use of antipsychotic medications: rational management of irrationality. 2012

  22. Adverse Drug EventsRisk vs. Benefit Risk of Mortality Among individual Antipsychotics in Patients with Dementia Design: Retrospective cohort study (Dept of Veterans Affairs 1999-2006) Population: Patients with dementia≥ 65 years of age Sample size: 33,604 patients • Primary outcome • 180 day mortality rate • Medications Evaluated • -risperidone • -olanzapine • Quetiapine • haloperidol Results: 1.5 fold increase in mortality associated with use of haloperidol when compared to atypicals

  23. Current Guidance-Agency on Healthcare Research and Quality (AHRQ) Comparative Effectiveness Review ofOff label use of Atypical Antipsychotics Small Statistically significant effect Risperidone, aripiprazole and olanzapine have some efficacy in treating behavioral sx in dementia AHRQ Publication No 11EHC087-EF

  24. Atypical Antipsychotics – Consensus? • Organization- Year- Country - Recommendations regarding antipsychotic use in dementia • ASCP 2011 USA - 2nd Line: “Only for the duration needed, and at the lowest effective dose” • APA 2007 USA -2nd Line: “Recommended for the treatment of psychosis and agitation in dementia” • AGS 2011 USA - 2nd Line: “May be needed for treatment of distressing delusions and hallucinations” • NICE 2006 UK- 2nd Line: “Risk benefit analysis should occur prior to use” • CCSMH 2006 Canada 2nd Line:“Atypical antipsychotics should only be used if there is marked risk, disability or suffering associated with the symptoms” • EFNS 2007 Europe- 2nd Line:“Antipsychotics, conventional as well as atypical, • may be associated with significant side effects and • should be used with caution” American Society of Consultant Pharmacists, position statement, 2011 Aging Res Rev. 2012 Jan;11(1):78-86

  25. Summary and Key Points • Risperidone has the most evidence supporting efficacy in BPSD • THERE ARE NO FDA –APPROVED MEDICATIONS FOR BEHAVIORAL PROBLEM IN DEMENTIA • THERE IS NO CONCENSUS AMONG EXPERTS IN THE FIELD • Antipsychotics are 2ND LINE! • Only use drug therapy if behaviors cause severe distress on immediate risk

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