Benefits and risks of antipsychotic polypharmacy: An evidence-based review of the literature

Constantin Tranulis, Leila Skalli, Luc Nicole, Emmanuel Stip

Research output: Contribution to journalReview articlepeer-review

57 Citations (Scopus)


Combination antipsychotic prescription is an increasingly common practice in clinical psychiatry. This clinical practice is at odds with clinical guidelines promoting antipsychotic monotherapy. Moreover, there has been increased concern over the safety profile of atypical antipsychotics in the last 10-15 years. We reviewed the literature on antipsychotic combinations with a focus on safety and efficacy. Multiple electronic database searches were complemented by relevant bibliography cross-checking and expert discussions. The review showed a literature that is dominated by case reports and uncontrolled studies. Polypharmacy was unequally studied, with some recent combinations (i.e. clozapine and risperidone) being extensively, albeit inconclusively, studied and other more commonly used combinations (first- with second-generation agents) receiving little attention. From an evidence-based perspective, further trials of antipsychotic association of sufficient power to address safety issues are needed before recommending any antipsychotic combination. Particular weaknesses of the present literature are low number of participants, lack of adequate control of confounding variables, short duration of experimental follow-up and inadequate monitoring of potential adverse effects.

Original languageEnglish
Pages (from-to)7-20
Number of pages14
JournalDrug Safety
Issue number1
Publication statusPublished - 2008
Externally publishedYes


  • Amisulpride, drug interactions
  • Antipsychotics, drug interactions
  • Antipsychotics, therapeutic use
  • Benefit risk assessment
  • Clozapine, drug interactions
  • Drug interactions
  • Haloperidol, drug interactions
  • Olanzapine, drug interactions

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Pharmacology (medical)


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