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Published on: January 7, 2019
Atypical Antipsychotic Augmentation for Treatment-Resistant Depression: A Systematic Review and Network Meta-Analysis
Xinyu Zhou1, Gabor I Keitner1, Bin Qin1
1Department 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).
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.
