title: Atypical Antipsychotic Augmentation for Treatment-Resistant Depression: A Systematic Review and Network Meta-Analysis.
abstract: BACKGROUND
  Previous meta-analyses of atypical antipsychotics for depression were limited by few trials with direct comparisons between two treatments. We performed a network meta-analysis, which integrates direct and indirect evidence from randomized controlled trials (RCTs), to investigate the comparative efficacy and tolerability of adjunctive atypical antipsychotics for treatment-resistant depression (TRD).
  
  
  METHODS
  Systematic searches resulted in 18 RCTs (total n = 4422) of seven different types and different dosages of atypical antipsychotics and a placebo that were included in the review.
  
  
  RESULTS
  All standard-dose atypical antipsychotics were significantly more efficacious than placebo in the efficacy (standardized mean differences [SMDs] ranged from -0.27 to -0.43). There were no significant differences between these drugs. Low-dose atypical antipsychotics were not significantly more efficacious than the placebo. In terms of tolerability, all standard-dose atypical antipsychotics, apart from risperidone, had significantly more side-effect discontinuations than placebo (odds ratios [ORs] ranged from 2.72 to 6.40). In terms of acceptability, only quetiapine (mean 250-350 mg daily) had significantly more all-cause discontinuation than placebo (OR = 1.89). In terms of quality of life/functioning, standard-dose risperidone and standard-dose aripiprazole were more beneficial than placebo (SMD = -0.38; SMD = -0.26, respectively), and standard-dose risperidone was superior to quetiapine (mean 250-350 mg daily).
  
  
  CONCLUSIONS
  All standard-dose atypical antipsychotics for the adjunctive treatment of TRD are efficacious in reducing depressive symptoms. Risperidone and aripiprazole also showed benefits in improving the quality of life of patients. Atypical antipsychotics should be prescribed with caution due to abundant evidence of side effects.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Zhou, Qin, Liu, Zhang, and Xie); Department of Psychiatry and Human Behavior, Rhode Island and Miriam Hospitals, Brown University, Providence, RI (Dr Keitner); Department of Psychiatry, University of Toronto and Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health, Toronto, Canada (Dr Ravindran); Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany (Dr Bauer); Department of Diagnostic, Clinical, and Public Health Medicine, Italian Cochrane Centre, University of Modena and Reggio, Emilia, Modena, Italy (Dr Del Giovane); Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Dr Zhao); Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Dr Fang).
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Zhou, Qin, Liu, Zhang, and Xie); Department of Psychiatry and Human Behavior, Rhode Island and Miriam Hospitals, Brown University, Providence, RI (Dr Keitner); Department of Psychiatry, University of Toronto and Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health, Toronto, Canada (Dr Ravindran); Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany (Dr Bauer); Department of Diagnostic, Clinical, and Public Health Medicine, Italian Cochrane Centre, University of Modena and Reggio, Emilia, Modena, Italy (Dr Del Giovane); Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Dr Zhao); Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Dr Fang).
authors.forename: Gabor I
authors.initials: GI
authors.lastname: Keitner
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Zhou, Qin, Liu, Zhang, and Xie); Department of Psychiatry and Human Behavior, Rhode Island and Miriam Hospitals, Brown University, Providence, RI (Dr Keitner); Department of Psychiatry, University of Toronto and Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health, Toronto, Canada (Dr Ravindran); Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany (Dr Bauer); Department of Diagnostic, Clinical, and Public Health Medicine, Italian Cochrane Centre, University of Modena and Reggio, Emilia, Modena, Italy (Dr Del Giovane); Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Dr Zhao); Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Dr Fang).
authors.forename: Bin
authors.initials: B
authors.lastname: Qin
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Zhou, Qin, Liu, Zhang, and Xie); Department of Psychiatry and Human Behavior, Rhode Island and Miriam Hospitals, Brown University, Providence, RI (Dr Keitner); Department of Psychiatry, University of Toronto and Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health, Toronto, Canada (Dr Ravindran); Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany (Dr Bauer); Department of Diagnostic, Clinical, and Public Health Medicine, Italian Cochrane Centre, University of Modena and Reggio, Emilia, Modena, Italy (Dr Del Giovane); Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Dr Zhao); Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Dr Fang).
authors.forename: Arun V
authors.initials: AV
authors.lastname: Ravindran
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Zhou, Qin, Liu, Zhang, and Xie); Department of Psychiatry and Human Behavior, Rhode Island and Miriam Hospitals, Brown University, Providence, RI (Dr Keitner); Department of Psychiatry, University of Toronto and Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health, Toronto, Canada (Dr Ravindran); Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany (Dr Bauer); Department of Diagnostic, Clinical, and Public Health Medicine, Italian Cochrane Centre, University of Modena and Reggio, Emilia, Modena, Italy (Dr Del Giovane); Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Dr Zhao); Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Dr Fang).
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Zhou, Qin, Liu, Zhang, and Xie); Department of Psychiatry and Human Behavior, Rhode Island and Miriam Hospitals, Brown University, Providence, RI (Dr Keitner); Department of Psychiatry, University of Toronto and Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health, Toronto, Canada (Dr Ravindran); Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany (Dr Bauer); Department of Diagnostic, Clinical, and Public Health Medicine, Italian Cochrane Centre, University of Modena and Reggio, Emilia, Modena, Italy (Dr Del Giovane); Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Dr Zhao); Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Dr Fang).
authors.forename: Cinzia
authors.initials: C
authors.lastname: Del Giovane
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Zhou, Qin, Liu, Zhang, and Xie); Department of Psychiatry and Human Behavior, Rhode Island and Miriam Hospitals, Brown University, Providence, RI (Dr Keitner); Department of Psychiatry, University of Toronto and Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health, Toronto, Canada (Dr Ravindran); Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany (Dr Bauer); Department of Diagnostic, Clinical, and Public Health Medicine, Italian Cochrane Centre, University of Modena and Reggio, Emilia, Modena, Italy (Dr Del Giovane); Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Dr Zhao); Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Dr Fang).
authors.forename: Jingping
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Zhou, Qin, Liu, Zhang, and Xie); Department of Psychiatry and Human Behavior, Rhode Island and Miriam Hospitals, Brown University, Providence, RI (Dr Keitner); Department of Psychiatry, University of Toronto and Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health, Toronto, Canada (Dr Ravindran); Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany (Dr Bauer); Department of Diagnostic, Clinical, and Public Health Medicine, Italian Cochrane Centre, University of Modena and Reggio, Emilia, Modena, Italy (Dr Del Giovane); Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Dr Zhao); Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Dr Fang).
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Zhou, Qin, Liu, Zhang, and Xie); Department of Psychiatry and Human Behavior, Rhode Island and Miriam Hospitals, Brown University, Providence, RI (Dr Keitner); Department of Psychiatry, University of Toronto and Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health, Toronto, Canada (Dr Ravindran); Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany (Dr Bauer); Department of Diagnostic, Clinical, and Public Health Medicine, Italian Cochrane Centre, University of Modena and Reggio, Emilia, Modena, Italy (Dr Del Giovane); Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Dr Zhao); Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Dr Fang).
authors.forename: Yiru
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Zhou, Qin, Liu, Zhang, and Xie); Department of Psychiatry and Human Behavior, Rhode Island and Miriam Hospitals, Brown University, Providence, RI (Dr Keitner); Department of Psychiatry, University of Toronto and Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health, Toronto, Canada (Dr Ravindran); Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany (Dr Bauer); Department of Diagnostic, Clinical, and Public Health Medicine, Italian Cochrane Centre, University of Modena and Reggio, Emilia, Modena, Italy (Dr Del Giovane); Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Dr Zhao); Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Dr Fang).
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Drs Zhou, Qin, Liu, Zhang, and Xie); Department of Psychiatry and Human Behavior, Rhode Island and Miriam Hospitals, Brown University, Providence, RI (Dr Keitner); Department of Psychiatry, University of Toronto and Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health, Toronto, Canada (Dr Ravindran); Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany (Dr Bauer); Department of Diagnostic, Clinical, and Public Health Medicine, Italian Cochrane Centre, University of Modena and Reggio, Emilia, Modena, Italy (Dr Del Giovane); Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Dr Zhao); Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Dr Fang). xiepeng973@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents
keywords: Atypical antipsychotics; network meta-analysis; systematic review; treatment-resistant depression