Treatment Options for the Management of Behavioral and Psychological Symptoms of Dementia

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The term behavioral and psychological symptoms of dementia (BPSD) describes a constellation of symptoms and behaviors that occur in >90% of individuals with dementia.¹ Apathy is the most common BPSD seen among individuals with Alzheimer disease (AD), whereas depression is the most common BPSD observed among individuals with vascular dementia (VD). Anxiety is the most common BPSD noted in individuals with dementia with Lewy bodies (DLB), and agitation and aggression are the most common BPSD identified among individuals with frontotemporal dementia (FTD). BPSD is associated with a faster decline in cognition and function among individuals with dementia.¹ This decline often results in the placement of those with dementia in care facilities. Additionally, BPSD contributes directly and indirectly to one-third of the cost of caring for individuals with dementia because of the greater utilization of health resources and services. Furthermore, BPSD adds significantly to increased distress and depression among caregivers of individuals with dementia. Finally, BPSD contributes significantly to the greater rates morbidity and mortality among those with dementia.

Available evidence indicates efficacy for both nonpharmacological and pharmacological treatments for BPSD.² The use of pharmacotherapy is usually reserved for those who have not responded adequately to nonpharmacological treatments. Nonpharmacological interventions are the recommended first line treatment recommended for BPSD.

Evidence for Nonpharmacological Interventions

One meta-analysis by Brodaty and Arasartnam found that interventions like skills training for caregivers, education of caregivers, activity planning and environmental design, enhancing support for caregivers, self-care technique for caregivers, and collaborative care not only reduced the frequency and severity of BPSD (effect size=0.34, P<0.01), but also reduced the caregiver burden (effect size=0.15, P=0.006).³ Another meta-analysis found that a multidisciplinary care [standardized mean difference (SMD)=-0.5], massage and touch therapy (SMD=-0.75) and music combined with massage and touch therapy (SMD=-0.91) were found to be more efficacious than usual care for the management of agitation and aggression among those with dementia.⁴ A third meta-analysis found benefits for massage therapy (SMD=−0.77), animal-assisted intervention (SMD=−0.47), personally tailored intervention (SMD = −0.39), pet robot intervention (SMD=−0.38), massage therapy (SMD=−5.220), light therapy (SMD=−5.25), music therapy (SMD=−3.61), reminiscence therapy (SMD=−4.59), animal-assisted intervention (SMD=−3.14) and personally tailored intervention (SMD=−2.98) for the management of agitation in dementia when compared to the control group.⁵ A fourth meta-analysis found that interventions that are tailored to involve activities based on the abilities and interests of individual with BPSD, and education and support that is offered to meet the needs of caregivers are more effective in reducing symptoms of BPSD, when compared with standardized intervention (SMD = -0.24, P=0.04).⁶

Pharmacological Interventions

Data from the meta-analysis by Trinh et al indicated that individuals with BPSD who received acetylcholinesterase inhibitors did better on the Neuropsychiatric Inventory (NPI) scale by 1.72 points, when compared with individuals who received receiving placebo indicating a small, but statistically significant benefit.⁷ Another meta-analysis found that individuals with BPSD who received memantine did better by 1.99 points on the NPI scale, when compared with people receiving placebo (P=0.04).⁸ A meta-analysis by Seitz et al found that individuals with BPSD who received sertraline and fluoxetine did better than those individuals who received placebo on the Cohen Mansfield Agitation Inventory [CMAI (mean difference (MD)=-0.89, P<0.001].⁹ A meta-analysis by Bhaji et al indicated benefits for cannabinoids on the CMAI (SMD=−0.80), the NPI total score (SMD=−0.61), the neuropsychiatric inventory-nursing home (NPI-NH)-Agitation/Aggression sub-score (SMD=−0.61), and on nocturnal motor activity (SMD=−1.05) among individuals with BPSD. A meta-analysis by Vacas et alfound benefits for rTMS, among individuals with BPSD (overall effect=−0.58, P=0.01).¹⁰

The Role of Antipsychotics

Yunusa et al in their meta-analysis found benefits for aripiprazole among individuals BPSD, when compared with placebo on the NPI (SMD=−0.17), the BPRS (SMD= −0.20), and on the CMAI (SMD=−0.30).¹¹ The investigators also found benefits for quetiapine on the BPRS (SMD=−0.24) and risperidone on the CMAI (SMD=−0.26), when compared with placebo. In this meta-analysis, the investigators did not find a greater risk of death with any of the antipsychotics compared with placebo. They noted a greater risk for cerebrovascular events (CVAEs) with olanzapine [odds ratio (OR)=4.28] and risperidone (OR=3.85) compared with placebo. Risperidone (OR=2.23) was noted to produce greater risk of extrapyramidal symptoms (EPS) compared with placebo. Somnolence was greater for aripiprazole (OR=3.14), olanzapine (OR=4.08), quetiapine (OR=4.47), and risperidone (OR=2.57), when compared with placebo. Quetiapine (OR=2.11) was associated with increased urinary incontinence or urinary tract infections compared with placebo.

Yunusa et al found that when compared with placebo, aripiprazole (SMD=− 0.12) and olanzapine (SMD=−0.17) demonstrated small although nonsignificant numerical improvements in NPI-NH psychosis scores, whereas quetiapine (SMD=0.04) did not show any benefits among individuals with dementia related psychosis.¹² The investigators found that the odds of mortality were higher for aripiprazole (OR=1.58), brexpiprazole (OR=2.22), olanzapine (OR=2.21), quetiapine (OR=1.68), and risperidone (OR=1.63), when compared with placebo. The investigators also noted that the use of risperidone (OR=3.68) and olanzapine (OR=4.47) increased the odds of CVAEs compared with placebo. The odds of all-cause discontinuation were lower for aripiprazole (OR=0.71), but higher for brexpiprazole (OR=1.17), olanzapine (OR=1.14), and quetiapine (OR=1.01). Aripiprazole (OR=0.5) and olanzapine (OR=0.48) had lower odds of discontinuation due to lack of efficacy, when compared with placebo. The odds of discontinuation due to adverse effects were higher for olanzapine (OR=2.62), brexpiprazole (OR=1.80), quetiapine (OR=1.25), aripiprazole (OR=1.38) and risperidone (OR=1.41).

The US Food and Drug Administration (FDA) has a boxed warning for increased risk of death for both atypical and typical antipsychotic medications when they are used among older individuals with dementia.¹³

Dr Bachu is a psychiatrist at Baptist Health Behavioral Health Clinic in North Little Rock, AR. Dr Subhedar is a clinical extern at Saint Elizabeths Hospital in Washington, DC. Dr Ansari is a psychiatrist Pramukhswami Medical College in Anand, Gujarat, India. Dr Manoharan is a psychiatrist at Creighton University School of Medicine in Omaha, NE. Dr Tampi is professor and chairman of the Department of Psychiatry at Creighton University School of Medicine and Catholic Health Initiatives (CHI) Health Behavioral Health Services. He is also an adjunct professor of psychiatry at Yale School of Medicine in New Haven, Connecticut, and he is a member of the Psychiatric Times editorial board.

References

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2. Tampi RR, Bhattacharya G, Marpuri P. Managing behavioral and psychological symptoms of dementia (BPSD) in the era of boxed warnings. Curr Psychiatry Rep. 2022;24(9):431-440.

3. Brodaty H, Arasaratnam C. Meta-analysis of nonpharmacological interventions for neuropsychiatric symptoms of dementia. Am J Psychiatry. 2012;169(9):946-953.

4. Watt JA, Goodarzi Z, Veroniki AA, et al. Comparative efficacy of interventions for aggressive and agitated behaviors in dementia: a systematic review and network meta-analysis. Ann Intern Med. 2019;171(9):633-642.

5. Leng M, Zhao Y, Wang Z. Comparative efficacy of non-pharmacological interventions on agitation in people with dementia: a systematic review and Bayesian network meta-analysis. Int J Nurs Stud. 2020;102:103489.

6. Meng X, Su J, Li H, et al. Effectiveness of caregiver non-pharmacological interventions for behavioural and psychological symptoms of dementia: an updated meta-analysis. Ageing Res Rev. 2021;71:101448.

7. Trinh NH, Hoblyn J, Mohanty S, Yaffe K. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA. 2003;289(2):210-216.

8. Maidment ID, Fox CG, Boustani M, et al. Efficacy of memantine on behavioral and psychological symptoms related to dementia: a systematic meta-analysis. Ann Pharmacother. 2008;42(1):32-38.

9. Seitz DP, Adunuri N, Gill SS, et al. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011;(2):CD008191.

10. Vacas SM, Stella F, Loureiro JC, et al. Noninvasive brain stimulation for behavioural and psychological symptoms of dementia: a systematic review and meta-analysis. Int J Geriatr Psychiatry. 2019;34(9):1336-1345.

11. Yunusa I, Alsumali A, Garba AE, et al. Assessment of reported comparative effectiveness and safety of atypical antipsychotics in the treatment of behavioral and psychological symptoms of dementia: a network meta-analysis. JAMA Netw Open. 2019;2(3):e190828.

12. Yunusa I, Rashid N, Demos GN, et al. Comparative outcomes of commonly used off-label atypical antipsychotics in the treatment of dementia-related psychosis: a network meta-analysis. Adv Ther. 2022;39(5):1993-2008.

13. Mittal V, Kurup L, Williamson D, et al. Risk of cerebrovascular adverse events and death in elderly patients with dementia when treated with antipsychotic medications: a literature review of evidence. Am J Alzheimers Dis Other Demen. 2011;26(1):10-28.