title: 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.affiliation: Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China Center for Mental Health, Yanshan University, Qinhuangdao, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China Department of Psychiatry, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Zhengtu
authors.initials: Z
authors.lastname: Cong
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Third People's Hospital of Daqing, Daqing, China.
authors.forename: Wenhai
authors.initials: W
authors.lastname: Jiang
authors.affiliation: The Third People's Hospital of Daqing, Daqing, China.
authors.forename: Shuhe
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001526:Behavioral Symptoms / Q000188:drug therapy* / Q000209:etiology; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D003704:Dementia / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotic; clinical trial; dementia; meta-analysis