Psychiatric and Behavioral Symptoms in Alzheimer s and Other Dementias Aaron H. Kaufman, MD
Psychiatric and Behavioral Symptoms in Alzheimer s and Other Dementias Aaron H. Kaufman, M.D. Health Sciences Associate Clinical Professor Department of Psychiatry and Biobehavioral Sciences Geffen School of Medicine at UCLA September 10, 2016
Disclosures Research and Academic Support Industry Grant: ANS/St. Jude Medical - Deep Brain Stimulation for Treatment Resistant Depression (Sub-Investigator) collaboration with R. Espinoza, Principal Investigator Off-label use of medications for treatment will be discussed
Objectives At the end of this session, participants will be able to: Describe the most common psychiatric and behavioral symptoms encountered in individuals with dementia Consider some of the pharmacologic and nonpharmacologic options in the management of psychiatric and behavioral symptoms in individuals with dementia List some of the concerns with using antipsychotics for the management of behavioral symptoms
Case #1 Mr. J is an 84 year old gentleman with a 5 year history of cognitive impairment. His instrumental activities of daily living have been steadily declining He now requires a caregiver at home for assistance. He has lost motivation to participate in previous interests. He frequently wakes in the middle of the night.
Case #1 When Mr. J does awaken at night, he believes that his home is not his real home. He makes attempts to leave his residence in the middle of the night. On one occasion he thought he saw someone stealing from his home and he grabbed a kitchen knife for protection.
Older Americans 65+ years = 40.3 million in 2010 Represents 13.0% of the U.S. population, about one in every eight Americans By 2030, there will be about 71.5 million older persons, more than twice their number in 2000 People 65+ represented 12.4% of the population in the year 2000 but are expected to grow to be 20% of the population by 2030 Department of Health and Human Services - Administration on Aging http://www.aoa.gov/aoaroot/aging_statistics/census_population/census2010/index.aspx
Alzheimer s Disease Affects 1 in 8 older adults 5.4 million Americans have AD Rates increase with age http://www.alz.org/downloads/facts_figures_2012.pdf
Characterized by Dementia Decline in Cognition Decline in Activities of Daily Living Behavioral and Psychiatric Symptoms Hersch EC & Falzgraf S. Clinical Interventions in Aging 2007 De Dyn 2005
Behavioral and Psychiatric Symptoms in Dementia (BPSD) Agitation Aggressive Physical Aggression Vocalizing/Shouting Verbal Insults Non-Aggressive Pacing Restlessness Wandering Purposeless motor behavior Psychosis Delusions Hallucinations Mood/Anxiety/Sleep Depression Euphoria Apathy Irritability Sleep disturbance Appetite/eating Obsessive ruminations Personality Changes Disinhibition Withdrawal Hypersexuality
Why are BPSD Important? Distressing for patient Distressing for family and caregivers Caregiver burnout Caregiver depression Reduced quality of life Increase in risk for institutionalization Ballard CG, et al. Curr Opin Psychiatry 2009 Gilley DW 1991, Rabins PV 1982 Ballard CG 2001, Banerjee S 2006 Steele C 1990
How Common are BPSD? At least 80-90% experience at least 1 symptom during the course of dementia Agitation/Aggression 20% of patients with AD in clinical settings 40-60% of patients in Long Term Care Psychosis 25% of patients in clinical settings Depression 20% of patients in clinical settings Ballard CG, et al. Curr Opin Psychiatry 2009 Steinberg M 2008, Aalten P 2003 Lyketsos CG 2000, Margallo-Lana M 2001 Burns A 1990
Cache County Study of Memory in Aging Study of elderly residents of Cache County, Utah Over 5000 screened for cognitive impairment Evaluated prevalence of behavioral symptoms in the elderly 329 with dementia compared to 673 without dementia Lyketsos CG, et al. Am J Psychiatry 2000
30 25 Cache County X-Axis NPI Item 1 Apathy 2 Depression 3 Agitation 4 Irritability 5 Delusions 6 Anxiety 7 Motor 8 Hallucinations 9 Disinhibition 10 Elation 20 15 10 Dementia No Dementia 5 0 1 2 3 4 5 6 7 8 9 10 Lyketsos CG, et al. Am J Psychiatry 2000
Assessment of BPSD New Symptom Delirium Pain Sensory Deficit Dementia
Non-pharmacologic Treatment Aromatherapy 4 RCTs (< 4-12 weeks) 2 with Lavender oil 2 with Melissa oil Safe +/- efficacy Bright Light Therapy 3 controlled trials for sleep disturbance and restlessness Some benefit for restlessness Safe Ballard CG, et al. International Review of Psychiatry 2008 Burns A 2002, Ballard CG 2002, Burns A, et al. Dement Geriatr Cogn Disord 2011
Non-pharmacologic Treatment Reminiscence Personalized music Structured social activities Person centered bathing Pet therapy Others
Pharmacologic Treatment of Aggression & Agitation 1st Generation Antipsychotics Several trials for BPSD Best studied is Haloperidol Length of trials 4-12 weeks (+) Aggression (+/-) Psychosis (-) Non-aggressive agitation Side effects include acute dystonias, extrapyramidal side effects, tardive dyskinesia Ballard CG and Corbett A. CNS Drugs 2010 Lonergan E 2005.
Pharmacologic Treatment of Aggression & Agitation 2nd Generation Antipsychotics Several trials for BPSD Length of trials 6-12 weeks Side effects include weight gain, dyslipidemia, sedation, orthostatic hypotension and others Ballard CG and Corbett A. CNS Drugs 2010
Pharmacologic Treatment of Aggression & Agitation 2nd Generation Antipsychotics Risperidone (+) Aggression at 2 mg/day (+) Psychosis at 1 mg/day (-) Non-aggressive agitation Aripiprazole (+) Aggression (+) Psychosis at 10 mg/day Quetiapine (-) Agitation Olanzapine (+/-) Agitation/aggression/psychosis at 5-10 mg/day Ballard CG and Corbett A. CNS Drugs 2010
Pharmacologic Treatment of Aggression & Agitation Clinical Antipsychotic Trials of Intervention Effectiveness Study (CATIE-AD) Compared Risperidone, Olanzapine, Quetiapine and Placebo Primary Phase 1 Outcome: Time until discontinuation of agents For discontinuation due to lack of efficacy Risperidone 26.7 weeks, mean last prescribed dose 1 mg/day Olanzapine 22.1 weeks, mean last prescribed dose 5.5 mg/day Quetiapine 9.1 weeks, mean last prescribed dose 56.5 mg/day Placebo 9.0 weeks Discontinuations due to intolerability Risperidone 18% Olanzapine 24% Quetiapine 16% Placebo 5% Sultzer DL, et al. Am J Psychiatry 2008. Schneider LS, et al. N Engl J Med 2006.
Pharmacologic Treatment of Aggression & Agitation Antipsychotics carry risk! Mortality risk Cardiovascular risk Decreased cognition Falls Edema Pneumonia Ballard CG and Corbett A. CNS Drugs 2010 FDA 2005. Schneider LS 2005. Wang PS 2005. Ballard C 2009 McShane R 1997. Ballard C 2005 Schneider LS 2006. Ballard C 2006
Pharmacologic Treatment of Aggression & Agitation Cholinesterase Inhibitors Small effect overall No acute benefit Possibly helpful for psychosis in DLB Memantine Some benefit possibly over 3-6 months in AD Unclear role thus far Antidepressants Citalopram 17 day trial in acute inpatients showed benefit Trazodone Studies suggest benefit, but double blind trial negative Anticonvulsants Carbamazepine 2 small studies were positive Valproate Disappointing results Oxcarbazepine Single study with trend toward improvement Gabapentin Minimal data Benzodiazepines Possibly helpful, but risks of sedation, falls, worsening cognition, disinhibition Alpha-blockers Prazosin Small 8-week trial showing benefit Ballard CG, et al. Curr Opin Psychiatry 2009 Corbett A, et al. Curr Treat Options Neurol 2012
Pharmacologic Treatment of Depression Antidepressants SSRIs (+/-) Sertraline (-) Fluoxetine TCAs (+) Clomipramine (-) Imipramine SNRIs No data Other - (-) Mirtazapine No trials for Vascular Dementia No trials for Dementia with Lewy Bodies Ballard CG, et al. Curr Opin Psychiatry 2009 Bains J 2007. Petracca G 1996. Reifler BV 1989 Petracca GM 2001. Lyketsos CG 2003 Banerjee S, et al. Lancet 2011.
Pharmacologic Considerations Citalopram/Sertraline Depression, irritability, anxiety and sleep disturbance. Trazodone Sleep disturbance, agitation Benzodiazepines Anxiety, agitation, but beware falls, sedation, worsening cognition, disinhibition Risperidone/Olanzapine/Aripiprazole Aggression, agitation and psychosis, but only for severe symptoms and ideally for short term only Cholinesterase Inhibitors Consider if not already added for AD +/- memantine
Principles of Treatment Non-Pharmacologic treatments are 1 st line Many symptoms have remissions or fluctuate and may improve over several weeks If pharmacologic interventions pursued: Start with least harmful and progress If treatment carries risk, discuss with patient/family Make attempts at withdrawing therapy, if possible
Recommended Reading Ballard C and Corbett A. Management of neuropsychiatric symptoms in people with dementia. CNS Drugs 2010; 24 (9): 729-739. Ballard C, et al. Management of agitation and aggression associated with Alzheimer s disease: controversies and possible solutions. Current Opinion in Psychiatry 2009; 22: 532-540. Corbett A, et al. Treatment of behavioral and psychological symptoms of Alzheimer s disease. Current Treatment Options in Neurology 2012; 14: 113-125. Reus VI, et al. The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients with Dementia. The American Journal of Psychiatry 2016; 173(5):543-6.
Questions? Aaron H. Kaufman, M.D. Health Sciences Associate Clinical Professor Department of Psychiatry and Biobehavioral Sciences Semel Institute of Neuroscience and Human Behavior David Geffen School of Medicine at UCLA 310.825.9159 akaufman@mednet.ucla.edu