Comparative Efficacy and Safety of Pharmacological and Non-pharmacological Interventions in Persons Living with Dementia

Background: Neuropsychiatric symptoms of dementia are treated with pharmacological and non-pharmacological interventions; however, their comparative efficacy and safety is largely unknown. As practice patterns shift because of concerns regarding antipsychotic safety, we need to understand the efficacy and safety of alternative interventions. Methods: Outcomes for this thesis were chosen by dementia care partners. Three studies were conducted: a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing the efficacy of pharmacological and non-pharmacological interventions for treating aggression and agitation in PLWD, a systematic review and NMA of RCTs and non-randomized studies (NRSs) comparing the safety (i.e. fracture, cerebrovascular event, fall, or mortality risk) of pharmacological interventions used to treat neuropsychiatric symptoms in PLWD, and a retrospective cohort study comparing the risk of major osteoporotic fractures, falls, and death associated with trazodone or atypical antipsychotic use in PLWD. Results: Non-pharmacological interventions were as, or more, efficacious than pharmacological interventions for treating aggression and agitation in PLWD. No pharmacological interventions were associated with increased odds of fracture among PLWD. Compared to placebo, cholinesterase inhibitors were associated with decreased odds of death (odds ratio (OR) 0.82, 95% credible interval (CrI) 0.67 to 1), antipsychotics were associated with increased odds of cerebrovascular events (OR 2.19, 95% CrI 1.3 to 3.79), and dextromethorphan-quinidine was associated with increased odds of falls (OR 4.16, 95% CrI 1.47 to 14.22) in NMAs of RCT data. These associations were not seen in NRS data. Compared to atypical antipsychotics, trazodone was associated with a similar rate of falls and major osteoporotic fractures (weighted hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.73 to 1.07); however, it was associated with a lower rate of mortality (weighted HR 0.75, 95% CI 0.66 to 0.85) in PLWD. Conclusion: Non-pharmacological rather than pharmacological interventions should be used for treating aggression and agitation in PLWD. Comparable rates of falls and fractures associated with trazodone or atypical antipsychotic use suggests a shift in prescribing to trazodone may not be entirely approproriate. Data comparing the safety of antipsychotics to other interventions was sparse. More studies comparing antipsychotics to alternative interventions are needed.Ph.D.2020-07-21 00:00:0