SynthesisThe international journal of neuropsychopharmacology2015
Atypical Antipsychotic Augmentation for Treatment-Resistant Depression: A Systematic Review and Network Meta-Analysis.
Open access · goldAbstract readSystematic ReviewNetwork Meta-Analysis
In one paragraph
Synthesis in The international journal of neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 8 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 8 pooled it
14.3field-weighted citation impact, top 1% of its field
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
70 citing papers in PubMed, 8 syntheses or guidelines pooled it, 191 citations in OpenAlex.
- Antidepressive Effect of Antipsychotics in the Treatment of Schizophrenia: Meta-Regression Analysis of Randomized Placebo-Controlled Trials.The international journal of neuropsychopharmacology · 2021Pooled it
- Adjunctive Vagus Nerve Stimulation for Treatment-Resistant Depression: a Quantitative Analysis.The Psychiatric quarterly · 2020Pooled it
- Treatment Response of Add-On Esketamine Nasal Spray in Resistant Major Depression in Relation to Add-On Second-Generation Antipsychotic Treatment.The international journal of neuropsychopharmacology · 2020Pooled it
- Pharmacological interventions for treatment-resistant depression in adults.The Cochrane database of systematic reviews · 2019Pooled it
- Vortioxetine treatment for generalised anxiety disorder: a meta-analysis of anxiety, quality of life and safety outcomes.BMJ open · 2019Pooled it
- Brexpiprazole as Adjunctive Treatment for Major Depressive Disorder Following Treatment Failure With at Least One Antidepressant in the Current Episode: a Systematic Review and Meta-Analysis.The international journal of neuropsychopharmacology · 2019Pooled it
- Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2016Pooled it
- Antipsychotics for fibromyalgia in adults.The Cochrane database of systematic reviews · 2016Pooled it
- Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial.Nature medicine · 2026Trial
- Repetitive Transcranial Magnetic Stimulation as Maintenance Treatment of Depression: The MAINT-R Randomized Clinical Trial.JAMA network open · 2025Trial
- The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users.Translational psychiatry · 2023Trial
- Efficacy and Safety of Lumateperone and Other Atypical Antipsychotics Approved as Adjunctive Treatment for Major Depressive Disorder in the United States: A Network Meta-Analysis.Advances in therapy · 2026Article
- Second-Generation Antipsychotics for Depression in Serious Illness: A First-Line Augmentation Strategy.Journal of pain and symptom management · 2026Review
- Disease-specific therapeutic plasma concentration ranges for quetiapine in schizophrenia, manic episode, depressive episode, and depressive comorbid insomnia.Discover mental health · 2026Article
- Sympathetic activation but not dissociation linked to ketamine's sustained antidepressant effect.Therapeutic advances in psychopharmacology · 2026Article
- Co-Administration Treatment in Drug-Naïve Major Depression: Exploratory Real-World Patterns and Predictors in China.Neuropsychiatric disease and treatment · 2026Article
- A high-power near-infrared photobiomodulation device: design, fabrication, and primary impact on treatment-resistant depression.Lasers in medical science · 2025Article
- Randomized, placebo-controlled, double-blind clinical trial on the contributions of vitamin D in the control of cardiovascular risk factors, depressive symptoms and suicide risk.American heart journal plus : cardiology research and practice · 2025Article
- Chronic Quetiapine Administration Has a Therapeutic Effect on Anxiety and Depression-Like Behavior in a Chronic Unpredictable Mild Stress (CUMS) Rat Model.Brain and behavior · 2025Article
- Generalizability of Risk Models for Treatment-Resistant Depression Across Three Health Systems.medRxiv : the preprint server for health sciences · 2025Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 10 institutions in 5 countries.
Xinyu ZhouDepartment 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).
Gabor I KeitnerDepartment 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).
Bin QinDepartment 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).
Arun V RavindranDepartment 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).
Michael BauerDepartment 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).
Cinzia Del GiovaneDepartment 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).
Jingping ZhaoDepartment 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).
Yiyun LiuDepartment 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).
Yiru FangDepartment 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).
Yuqing ZhangDepartment 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).
Peng XieDepartment 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.
Central South University · CNBrown University · USChongqing Medical University · CNFirst Affiliated Hospital of Chongqing Medical University · CNMiriam Hospital · USSecond Xiangya Hospital of Central South University · CNTU Dresden · DEUniversity Hospital Carl Gustav Carus · DEUniversity of Modena and Reggio Emilia · ITUniversity of Toronto · CA
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrevious 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).
methodsSystematic 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.
resultsAll 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).
conclusionsAll 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.
Indexed as
AdolescentAdultAgedAntipsychotic AgentsDepressive Disorder, Treatment-ResistantFemaleHumansMaleMiddle AgedRandomized Controlled Trials as TopicYoung AdultAntipsychotic AgentsAtypical antipsychoticsnetwork meta-analysissystematic reviewtreatment-resistant depression
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