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.

• Authors: Hui Ma, Yinglin Huang, Zhengtu Cong, Yuan Wang, Wenhai Jiang, Shuhe Gao, Gang Zhu
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 42 Issue 3 Pg. 915-37 ( 2014) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 25024323 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents

Topics

• Antipsychotic Agents (therapeutic use)
• Behavioral Symptoms (drug therapy, etiology)
• Databases, Bibliographic (statistics & numerical data)
• Dementia (complications, drug therapy)
• Humans
• Neuropsychological Tests
• Psychiatric Status Rating Scales
• Psychotic Disorders (drug therapy, etiology)
• Randomized Controlled Trials as Topic