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Benefits and Risks of Antipsychotic Polypharmacy

An Evidence-Based Review of the Literature

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Abstract

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.

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Acknowledgements

This paper was partially supported by an unrestricted fellowship grant from Eli Lilly Schizophrenia Chair, University of Montreal, Canada for the first author. The funding organization had no role in the preparation of this manuscript. Constantin Tranulis declares no other conflicts of interest. Leila Skalli declares no conflicts of interest. Drs Lalonde, Nicole, Landry and Stip have received honoraria from various pharmaceutical companies, but none were related to the topic of the present paper.

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Tranulis, C., Skalli, L., Lalonde, P. et al. Benefits and Risks of Antipsychotic Polypharmacy. Drug-Safety 31, 7–20 (2008). https://doi.org/10.2165/00002018-200831010-00002

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