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Antipsychotic polypharmacy

What is antipsychotic polypharmacy?

Antipsychotic combination treatment, also called antipsychotic polypharmacy, has been utilised in clinical practice for patients who are unresponsive or partially responsive to antipsychotic monotherapies. Please also see the treatments for medication-resistant schizophrenia topic for augmentation with other pharmaceutical agents.

What is the evidence for antipsychotic polypharmacy?

Moderate to high quality evidence finds a medium-sized improvement in overall symptoms and a small improvement in clinical response with antipsychotic polypharmacy vs. monotherapy. There is also less discontinuation for any reason with antipsychotic polypharmacy. Moderate quality evidence finds antipsychotic polypharmacy is most often associated with the use of first-generation antipsychotics and with inpatient status and is higher in Asia and Europe than in North America and Oceania.

Moderate quality evidence finds augmenting any antipsychotic with aripiprazole can improve symptoms, particularly negative symptoms, when compared to antipsychotic monotherapy in open-label trials, but not when compared to adjunctive placebo in blinded trials.

For people with inadequate response to clozapine, moderate to high quality evidence finds augmenting clozapine with other second-generation antipsychotics may improve negative and depressive symptoms, but not necessarily positive symptoms. Adjunctive sulpiride and adjunctive ziprasidone were particularly effective for negative symptoms, and adjunctive aripiprazole and adjunctive ziprasidone were particularly effective for depressive symptoms. Moderate to low quality evidence finds improved total symptoms with clozapine augmentation of antidepressants fluoxetine, paroxetine and duloxetine. Adding topiramate, sodium valproate or lithium to clozapine may also improve total symptoms, while adding memantine may improve negative symptoms.

November 2019

Last updated at: 1:16 am, 27th November 2019
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Fact Sheet Technical Commentary

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Title Colour Legend:
Green - Topic summary is available.
Orange - Topic summary is being compiled.
Red - Topic summary has no current systematic review available.