CNS Drugs

, Volume 25, Issue 5, pp 383–399 | Cite as

Antipsychotic Polypharmacy in Schizophrenia

Benefits and Risks
  • Thomas R. E. BarnesEmail author
  • Carol Paton
Review Article


Antipsychotic polypharmacy refers to the co-prescription of more than one antipsychotic drug for an individual patient. Surveys of prescribing in psychiatric services internationally have identified the relatively frequent and consistent use of combined antipsychotics, usually for people with established schizophrenia, with a prevalence of up to 50% in some clinical settings. A common reason for prescribing more than one antipsychotic is to gain a greater or more rapid therapeutic response than has been achieved with antipsychotic monotherapy. However, the evidence on the risks and benefits for such a strategy is equivocal, and not generally considered adequate to warrant a recommendation for its use in routine clinical practice in psychiatry. Combined antipsychotics are a major contributor to high-dose prescribing, associated with an increased adverse effect burden, and of limited value in helping to establish the optimum maintenance regimen for a patient.

The relatively widespread use of antipsychotic polypharmacy identified in cross-sectional surveys reflects not only the addition of a second antipsychotic to boost therapeutic response, but also the use of as-required antipsychotic medication (mainly to treat disturbed behaviour), gradual cross-titration while switching from one antipsychotic to another, and augmentation of clozapine with a second antipsychotic where the illness has failed to respond adequately to an optimized trial of clozapine. This review addresses the clinical trial data and other evidence for each of these pharmacological approaches. Also reviewed are examples of systematic, practice-based interventions designed to reduce the prevalence of antipsychotic polypharmacy, most of which have met with only modest success.

Guidelines generally agree that if combined antipsychotics are prescribed to treat refractory psychotic illness, this should be after other, evidence-based, pharmacological treatments such as clozapine have been exhausted. Further, their prescription for each patient should be in the context of an individual trial, with monitoring of the clinical response and adverse effects, and appropriate physical health monitoring.


Clozapine Risperidone Aripiprazole Ziprasidone Amisulpride 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No sources of funding were used to prepare this review. Thomas R.E. Barnes has acted as an advisor to Johnson & Johnson, Servier and Bristol-Myers Squibb. Carol Paton has been an advisor to Eli-Lilly, Janssen-Cilag and Bristol-Myers Squibb with regard to antipsychotic medications.


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Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.Centre for Mental Health, Division of Experimental MedicineImperial College London, Charing Cross CampusLondonUK

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