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Related Experiment Video

Updated: Apr 11, 2026

Vagus Nerve Stimulation As an Adjunctive Neurostimulation Tool in Treatment-resistant Depression
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Atypical Antipsychotic Augmentation for Treatment-Resistant Depression: A Systematic Review and Network

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).

The International Journal of Neuropsychopharmacology
|May 28, 2015
PubMed
Summary

Standard-dose atypical antipsychotics effectively treat depression resistant to other therapies. However, caution is advised due to significant side effects and discontinuation rates, with some drugs improving quality of life.

Keywords:
Atypical antipsychoticsnetwork meta-analysissystematic reviewtreatment-resistant depression

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Area of Science:

  • Psychiatry
  • Pharmacology
  • Clinical Medicine

Background:

  • Previous meta-analyses on atypical antipsychotics for depression had limited direct treatment comparisons.
  • Network meta-analysis was employed to integrate direct and indirect evidence from randomized controlled trials (RCTs).

Purpose of the Study:

  • To investigate the comparative efficacy and tolerability of adjunctive atypical antipsychotics for treatment-resistant depression (TRD).
  • To assess the impact of different atypical antipsychotics on depressive symptoms, side effects, acceptability, and quality of life.

Main Methods:

  • Systematic searches identified 18 RCTs involving 4422 participants.
  • Seven atypical antipsychotics at various dosages and placebo were compared.

Main Results:

  • Standard-dose atypical antipsychotics were significantly more efficacious than placebo (SMDs -0.27 to -0.43), with no significant differences among them.
  • Low-dose atypical antipsychotics showed no significant efficacy over placebo.
  • Most standard-dose atypical antipsychotics (except risperidone) had significantly more side-effect discontinuations than placebo (ORs 2.72 to 6.40).
  • Quetiapine (250-350 mg daily) showed significantly higher all-cause discontinuation rates (OR = 1.89).
  • Standard-dose risperidone and aripiprazole improved quality of life/functioning compared to placebo (SMD -0.38 and -0.26, respectively).
  • Standard-dose risperidone was superior to quetiapine (250-350 mg daily) in quality of life/functioning.

Conclusions:

  • Standard-dose atypical antipsychotics are efficacious as adjunctive treatment for TRD, reducing depressive symptoms.
  • Risperidone and aripiprazole demonstrated benefits in improving patient quality of life.
  • Prescribing atypical antipsychotics requires caution due to substantial evidence of side effects.