Antipsychotic polypharmacy in schizophrenia: evolving evidence and rationale

ABSTRACT

Introduction

Antipsychotic polypharmacy (APP), defined as the use of more than one antipsychotic, is common in schizophrenia. However, current guidelines consider that the level of evidence to support APP is weak and mostly recommend monotherapy.

Areas covered

Meta-analyses of randomized controlled trials (RCTs) on the efficacy and tolerability of APP, effectiveness studies on its use in clinical practice, as well as theoretical models liable to legitimate this use are reviewed and discussed on the basis of a systematic literature search (PubMed) ranging from 1995 to 2020.

Expert opinion

There is now increasing evidence from both efficacy and effectiveness studies, that APP may be beneficial for some schizophrenia patients. The most evidence seems to be for the combination of clozapine and aripiprazole. The choice of this combination may fit in well with the dopamine supersensitivity hypothesis in schizophrenia. Guidelines should be revised, but further studies are needed to confirm the efficacy/effectiveness of this combination, especially in the case of first-episode schizophrenia.

KEYWORDS:

• Antipsychotic
• polypharmacy
• combination treatment
• augmentation

Article highlights

• Antipsychotic polypharmacy is common in schizophrenia

• Evidence for antipsychotic polypharmacy in schizophrenia is based on efficacy and effectiveness studies

• Among antipsychotic combinations, the most evidence is for clozapine + aripiprazole

• Antipsychotic combinations may help target a broader range of receptors

• Aripiprazole + clozapine could contribute to desensitizing dopamine D₂/D₃ receptors

This box summarizes key points contained in the article.

Declaration of interest

JM Azorin has received honoraria or research or educational conference grants from Brisyol Myers Squibb, Eli Lilly, Lundbeck, Otsuka, Takeda, Janssen, Novartis, Pfizer, AstraZeneca, Servier, and Sanofi Aventis. N Simon has received honoraria or research or educational conferences from Lundbeck, Otsuka, and Ethypharm. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership, or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.