7/2/2021 Managing Behavioral and Psychological Symptoms of Dementia (BPSD) in the Era of Boxed Warnings American Association for Geriatric Psychiatry (AAGP) Thursday, July 1, 2021, 6:00 pm-7:00 pm Pallavi Joshi, DO, MA (Chair) Rajesh R. Tampi, MD, MS, DFAPA, DFAAGP Shilpa Srinivasan, MD, DFAPA, DFAAGP 1 Objectives Objective One: To describe the epidemiology of BPSD Objective To elucidate the neurobiology and assessment of Two: individuals with BPSD Objective To discuss the management of individuals with Three: BPSD Objective To elaborate on the controversies in the treatment of Four: individuals BPSD 2 1 7/2/2021 Disclosures • There are no FDA approved medications for the treatment of behavioral and psychological symptoms of dementia and hence all medications discussed today are “Off Label” in their use • We have no conflicts of interest to disclose for this presentation 3 Pallavi Joshi, DO, MA 4 2 7/2/2021 Behavioral and Psychological Symptoms of Dementia • These are a heterogeneous range of psychological reactions, psychiatric symptoms and behaviors that may be unsafe, disruptive and impair the care of the patient in a given environment Barucha et al, CNS Spectrum, 2002 5 Prevalence • Community 65% have at least 1 disruptive behavior 40% have at least 3 disruptive behaviors • Nursing Homes 90% have at least 1 disruptive behaviors 45% have at least 4 disruptive behaviors • These behaviors are often chronic with different symptoms emerging as the illness progresses. • They also fluctuate with Psychomotor Agitation being the most persistent. Tampi et al, Clinical Geriatrics, 2011 6 3 7/2/2021 Classification Phenomenological Etiologic 1. Affective: depression, anxiety, 1. Primary: not due to any agitation, apathy, mania known etiology 2. Psychotic: delusions, 2. Secondary: due to an hallucinations underlying medical or psychiatric disorder 3. Sleep-Wake cycle disturbance 4. Behavioral: agitation, aggression, verbal disruption, impulsivity Tampi et al, Clinical Geriatrics, 2011 7 8 4 7/2/2021 Common BPSD Type of behaviors Prevalence Anxiety 21% to 60% Apathy 48% to 92% Delusions 16% to 70% Depression 30% to 50% Disinhibition/Impulsivity 30% to 35% Hallucinations 4% to 76% Inappropriate sexual behaviors 7% to 25% Mood lability 30% to 40% Sleep disturbance 20% to 25% Stereotyped behaviors 12% to 84% Weight loss 15% to 20% Tampi et al, Clinical Geriatrics, 2011 9 Impact of BPSD Diagnosis of dementia Direct and Caregiver indirect Indicates burden progression of cost of illness and care burnout Placement at facilities Tampi et al, Clinical Geriatrics, 2011 10 5 7/2/2021 Neurobiology • Psychotic symptoms → Frontal, temporal, limbic cortices • Apathy → Frontal lobes Biological (Anterior cingulate gyrus) • ApoE 3/4 homozygotes → Depression, anxiety, psychosis, agitation, sleep disorders • Serotonin and Dopamine receptor polymorphisms → BPSD Psychosis and aggression • Lower •First premorbid degree Genetic Psychological agreeablen relatives ess → → Agitation Depressio and n and irritability, psychosis Agitation/ Apathy Tampi et al, Clinical Geriatrics, 2011 syndrome 11 Assessment Obtain history (Medical, Psychiatric, Medications, Pre-morbid personality, Cognition, Functions) ↓ Complete a physical examination (Rule out underlying medical or neurological disorders) ↓ Order investigations (Blood tests, Urine examination, Vitamin B12 & Folate levels, VDRL, Neuroimaging) ↓ Complete standardized rating scales and or neuropsychological testing ↓ Medical/Neurological disorders→ Treat underlying disorder (s) ↓ Drug effect → Remove offending drug (s) ↓ Confirm BPSD Tampi et al, Clinical Geriatrics, 2011 12 6 7/2/2021 Management of Individuals with Behavioral and Psychological Symptoms of Dementia Rajesh R. Tampi, MD, MS, DFAPA, DFAAGP 13 Recognition is the first and the most important step in treatment Treatment should Educate always be caregivers individualized Review and Rule out and treat acknowledge the underlying medical relevant losses or conditions stressors Review Adapt to specific neuropsychiatric cognitive deficits diagnoses Assess and reverse aggravating factors Tampi et al, Clinical Geriatrics, 2011 14 7 7/2/2021 Non‐Pharmacological • Psychoeducation → Effective • Instruction for staff→ Effective Livingston G, Johnston K,• Cognitive stimulation therapy → May be Katona C, et al. 2005 effective • Therapeutic activities→ May be effective Systematic Review • Specialized dementia units → Not consistently beneficial, but may reduced wandering Brodaty H, Arasaratnam • Non-pharmacological interventions → Effect size of 0.34 (p<0.01) C. 2012 • Ameliorating caregiver reactions→ Effect Meta-analysis size of 0.15 (p=0.006) •Person-centered care, communication skills training Livingston G, Lewis- and adapted dementia care mapping → reduced agitation in care homes immediately (SES: 0.3-1.8) Holmes E, Baio S, et al. and for up to 6 months (SES: 0.2-2.2) •Activities and music therapy by protocol → reduced 2014 overall agitation (SES: 0.5-0.6) •Sensory intervention→ reduced agitation immediately Systematic Review •Aromatherapy and light therapy → No efficacy 15 Pharmacological • Only for symptoms that persist even after the non-pharmacological steps have been undertake • Conceptualized as a process of trial and error • Choice of medication may be influenced by the urgency of the situation • Behaviors may be classified as being emergent or non-emergent Tampi et al, Clinical Geriatrics, 2011 16 8 7/2/2021 Emergent behaviors May need to be treated with medications i.e., antipsychotics or need inpatient psychiatric treatment Non-emergent behaviors Cluster the most salient features into patterns that is roughly analogous to a drug responsive syndrome Appears depressed: Use antidepressants Appears hypomanic/manic: Use mood stabilizers or antipsychotics Appears psychotic: Use antipsychotics Tampi et al, Clinical Geriatrics, 2011 17 Prescribing Guidelines Select a medication class with some empirical evidence of The choice is some efficacy and the times influenced by a Start low and go slow highest likelihood of particular side effect tolerability and safety Frequently reassess Maintain at the sub- Avoid polypharmacy target symptoms and toxic levels for an if possible monitor for adverse appropriate period of effects (2-4 weeks) time (4-12 weeks) After the appropriate Sometimes several period (4-12 weeks), medication trials are Tampi et al, Clinical Geriatrics, 2011 try to taper dose, i.e., needed before the the empirical trial in problem is reverse ameliorated 18 9 7/2/2021 Typical Antipsychotics 11 randomized, placebo-controlled Modest advantage of typical antipsychotics trials over placebo (59% versus 41%) Haloperidol, 4 randomized controlled trials Small sample sizes (RCTs) 4 to 12 weeks in duration Significant improvement in symptoms of aggression with haloperidol compared with placebo A good outcome defined as a 30% improvement on standardized No substantial improvement with the drug in behavioral rating scales other symptoms of agitation Ballard CG, Gauthier S, Cummings JL, et al. 2009 19 Atypical Antipsychotics for Dementia: Meta‐Analysis Aripiprazole (48% vs. 38% and 61% vs. 54% for the NPI total and NPI psychosis subscales) Risperidone (46% vs. 33% pooled responders for BEHAVE-AD and 65% vs. 48% pooled responders for CGI) Efficacy Not for olanzapine or quetiapine There were smaller effects for less severe dementia, outpatients and patients selected for psychosis Approximately one-third dropped out without overall differences between drug and placebo Somnolence (OR 2.84 , 95% CI: 2.25–3.58) Urinary tract infection (OR: 1.28) Extrapyramidal symptoms with risperidone and olanzapine (OR: 1.51) Adverse Effects Abnormal gait with risperidone and olanzapine (OR: 3.42) Cognitive test scores worsened with drugs WMD of 0.73 Schneider L, Dagerman K, Insel PS. 2006 20 10 7/2/2021 Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. 42-site, double-blind, placebo- controlled trial for 36 weeks • Time to the discontinuation of treatment for any reason no different for drugs compared to placebo (P=0.52) 421 outpatients with Alzheimer's disease and psychosis, aggression, • The median time to the discontinuation of treatment due to lack of or agitation efficacy placebo =quetiapine; risperidone and olanzapine Randomly assigned to receive: >placebo Olanzapine (mean dose, 5.5 mg per day) • 3-5 times more individuals discontinued the drugs due to side- effects when compared to placebo (P=0.009) Quetiapine (mean dose, 56.5 mg per day) • Improvement on the CGIC scale no different between drugs and Risperidone (mean dose, 1.0 mg per placebo (P=0.22) day) Placebo The main outcomes were: 1. The time from initial treatment •No significant differences between antipsychotics and placebo on to the discontinuation of functioning, care needs, or quality of life treatment for any reason. •Cognitive function declined more in patients receiving antipsychotics on 2. The number of patients with multiple cognitive measures at least minimal •Treatment groups had significantly higher costs improvement on the Clinical Global Impression of •There were no cerebrovascular events or deaths that could be attributable to the drugs Change (CGIC) scale at 12 weeks. CATIE: Dementia study 21 Brexpiprazole • Two 12-week, randomized, double-blind, placebo-controlled, parallel-arm studies Study 1 Study 2 • 81 sites in 7 countries • 62 sites in 9 countries • 433 randomized • 270 randomized • Brexpiprazole 2 mg/day, brexpiprazole 1 mg/day, or • Brexpiprazole 0.5-2