Switching to antipsychotic monotherapy vs. staying on antipsychotic polypharmacy in schizophrenia: A systematic review and meta-analysis

Kentaro Matsui, Takahiro Tokumasu, Yoshiteru Takekita, Ken Inada, Tetsufumi Kanazawa, Taishiro Kishimoto, Shotaro Takasu, Hideaki Tani, Seiichiro Tarutani, Naoki Hashimoto, Hiroki Yamada, Yoshio Yamanouchi, Hiroyoshi Takeuchi

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Background: While recent meta-analyses have reported the superiority of antipsychotic polypharmacy (APP) over antipsychotic monotherapy (APM) in schizophrenia, switching to APM can be beneficial in terms of side effects. To determine whether patients receiving APP should switch to APM or stay on APP, we conducted a systematic review and meta-analysis. Methods: Randomized controlled trials (RCTs) examining a switch from APP to APM vs. staying on APP were systematically selected from a previous meta-analysis comparing APP with APM in patients with schizophrenia. In addition, we conducted an updated systematic literature search using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Data on study discontinuation, relapse, psychopathology, neurocognition, extrapyramidal symptoms, and body weight/body mass index (BMI) were extracted and synthesized. Results: A total of 6 RCTs involving 341 patients were included. All studies examined a switch from 2 antipsychotic agents to a single agent. Clozapine-treated patients were included in 3 studies. There was a significant difference in study discontinuation due to all causes in favor of staying on APP (N = 6, n = 341, RR = 2.28, 95% CI = 1.50–3.46, P < 0.001). There were no significant differences in relapse, any psychopathology, neurocognition, extrapyramidal symptoms, or body weight/BMI between the 2 groups. The quality of evidence was low to very low. Conclusions: The findings suggest that clinicians should closely monitor patient condition when switching to APM after receiving 2 antipsychotics. Given the low to very low overall quality of the evidence, the findings should be considered preliminary and inconclusive.

Original languageEnglish
Pages (from-to)50-57
Number of pages8
JournalSchizophrenia Research
Publication statusPublished - 2019 Jul


  • Antipsychotics
  • Combination
  • Monotherapy
  • Polypharmacy
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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