title: Efficacy and Safety of Adjunctive Aripiprazole in Schizophrenia: Meta-Analysis of Randomized Controlled Trials.
abstract: This meta-analysis of randomized controlled trials (RCTs) evaluated the efficacy and safety of adding aripiprazole to other antipsychotics in schizophrenia. A systematic computer search identified 55 RCTs including 4457 patients who were randomized to aripiprazole (14.0 ± 7.0 mg/d) versus placebo (18 RCTs) or open antipsychotic treatment (37 RCTs). Aripiprazole significantly outperformed the comparison interventions based on psychiatric scales: (1) total score in 43 RCTs (N = 3351) with a standardized mean difference (SMD) of -0.48 (95% confidence interval [CI], -0.68 to -0.28; P < 0.00001; I = 88%), (2) negative symptom score in 30 RCTs (N = 2294) with an SMD of -0.61(95% CI, -0.91 to -0.31; P < 0.00001; I = 91%), and (3) general psychopathology score in 13 RCTs (N = 1138) with a weighted mean difference (WMD) of -4.02 (95% CI, -7.23 to -0.81; P = 0.01; I = 99%), but not in positive symptoms in 29 RCTs (N = 2223) with a SMD of -0.01 (95% CI, 0.26 to 0.25; P = 0.95; I = 88%). Differences in total score based on psychiatric scales may be explained by the use of an antipsychotic for comparison rather than placebo in 31 RCTs with a nonblind design. Aripiprazole outperformed the comparison interventions for body weight in 9 RCTs (N = 505) with a WMD of -5.08 kg (95% CI, -7.14 to -3.02; P < 0.00001; I = 35%) and for body mass index (BMI) in 14 RCTs (N = 809) with a WMD of -1.78 (CI: -2.25 to -1.31; P < 0.00001; I = 54%). The BMI meta-regression analysis indicated aripiprazole's association with lower BMI was stronger in females. Adjunctive aripiprazole appears safe but better RCTs are needed to demonstrate efficacy. Chinese journals and scientific societies should encourage the publication of high-quality RCTs and require registration in a centralized Chinese database.
authors.affiliation: From *The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China; †Beijing Key Laboratory of Mental Disorders, Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China; ‡Center of Schizophrenia, Beijing Institute for Brain Disorders, Laboratory of Brain Disorders (Capital Medical University), Ministry of Science and Technology, Beijing, China; §Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA; ‖University of Kentucky, Mental Health Research Center at Eastern State Hospital, Lexington, KY; ¶Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada; and #Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apostol Hospital, University of the Basque Country, Vitoria, Spain.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Zheng
authors.forename: Xian-Bin
authors.initials: XB
authors.lastname: Li
authors.forename: Yi-Lang
authors.initials: YL
authors.lastname: Tang
authors.forename: Chuan-Yue
authors.initials: CY
authors.lastname: Wang
authors.forename: Ying-Qiang
authors.initials: YQ
authors.lastname: Xiang
authors.forename: Jose
authors.initials: J
authors.lastname: de Leon
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D000068180:Aripiprazole / Q000009:adverse effects / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D000068180:Aripiprazole