title: Antipsychotic Polypharmacy and Corrected QT Interval: A Systematic Review.
abstract: OBJECTIVE
  It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue.
  
  
  METHODS
  A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups.
  
  
  RESULTS
  A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy.
  
  
  CONCLUSIONS
  Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best.
authors.affiliation: Post-doctoral Fellow, Schizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, Ontario; Clinical Fellow, Department of Psychiatry, University of Toronto, Toronto, Ontario; Collaborative Researcher, Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Senior Lecturer, Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Lead, Schizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, Ontario; Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario; Professor, Institute of Medical Science, University of Toronto, Toronto, Ontario.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.affiliation: Senior Lecturer, Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.|Research Scientist, Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D019338:Polypharmacy
chemical_list: D014150:Antipsychotic Agents