The efficacy and safety of atypical antipsychotics for the treatment of dementia: a meta-analysis of randomized placebo-controlled trials

Abstract

Background: The application of atypical antipsychotics (SGAs) for treatment of psychiatric and behavioral symptoms of dementia is controversial since their efficacy might be offset by their adverse events (AEs).

Objective: To assess the efficacy, safety, and tolerability of SGAs for treatment of psychological and behavioral symptoms of dementia.

Methods: Two researchers searched MEDLINE, PsychINFO, and the Cochrane Central Register of Controlled Trials independently for double-blind, placebo-controlled, randomized controlled trials (DB-PC-RCTs) as of June 2013, written in English. Efficacy was measured using the Brief Psychiatric Rating Scale (BPRS), Cohen-Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory (NPI), Clinical Global Impression of Change (CGI-C), and (or) Clinical Global Impression of Severity (CGI-S). Safety and tolerability were measured by frequencies of drop-outs, AEs, and death. In total, 19 treatment comparisons drawn from 16 DB-PC-RCTs were included, and 3,343 patients randomized to the antipsychotic group and 1,707 to the placebo group were assessed.

Results: This meta-analysis demonstrated a significant efficacy of atypical antipsychotics on BPRS (MD = -1.58, 95% CI = -2.52 - -0.65), CMAI (-1.84, -3.01 - -0.61), NPI (-2.81, -4.35 - -1.28), CGI-C (-0.32, -0.44 - -0.20), and CGI-S (-0.19, -0.30 - -0.09), compared to placebo (p < 0.01 for all). Patients receiving atypical antipsychotics showed no difference in risk for discontinuation (p > 0.05), significantly higher risks (p < 0.05 for all) for somnolence (OR = 2.95), extrapyramidal symptoms (1.74), cerebrovascular AEs (2.50), urinary tract infection (1.35), edema (1.80), gait abnormality (3.35), and death (1.52), and a lower risk for agitation (OR = 0.80, p = 0.03).

Conclusions: The higher risks for AEs and mortality may offset the efficacy of atypical antipsychotics for treatment of dementia. Efficacy, safety, and tolerability thus should be carefully considered against clinical need.

Keywords: Antipsychotic; clinical trial; dementia; meta-analysis.