The Year in Psychiatry: Studies Not to Miss From 2011

Christoph U. Correll, MD; Maren Carbon, MD


November 23, 2011

In This Article

Can Antipsychotic Polypharmacy Be Safely Reduced in Schizophrenia?

Essock SM, Schooler NR, Stroup TS, et al; Schizophrenia Trials Network. Effectiveness of switching from antipsychotic polypharmacy to monotherapy. Am J Psychiatry. 2011;168:702-708.

Polypharmacy of antipsychotics is a frequently encountered practice in medicine but it lacks a clear evidence base. The concerns regarding polypharmacy include increased total antipsychotic dosages, drug-drug interactions, increased acute and chronic side effects, and reduced adherence. Studying the option of discontinuing polypharmacy in 127 schizophrenic patients taking 2 antipsychotics, Essock and colleagues conducted an open-label study with blinded ratings to investigate whether patients receiving 2 antipsychotics can be moved to antipsychotic monotherapy without loss of efficacy. All included patients had residual psychopathology at baseline, and medication intake was confirmed by corresponding serum levels. Furthermore, for those patients who were randomly assigned to discontinuation, this had to occur within 30 days. The patients and prescribers decided together which antipsychotic they discontinued, and participants had to continue with their assigned medication regimen for 6 months unless this treatment was clinically contraindicated. The main outcome measure was time to all-cause antipsychotic discontinuation. Medication dosing was not constrained by the study protocol; instead, treating clinicians used their clinical judgment to perform individual changes as needed. The most common antipsychotic combinations at baseline were a first-generation antipsychotic plus a second-generation antipsychotic or quetiapine plus risperidone.

The results indicated that patients switching to monotherapy had shorter times to all-cause treatment discontinuation than those assigned to stay on polypharmacy. By month 6, 86% of the stayers were still taking both medications, whereas 69% of the switchers to monotherapy were still taking the same medication. Most monotherapy discontinuations entailed returning to the original polypharmacy (12/18 = 66.7%), while most of the patients discontinuing antipsychotic polypharmacy (8/12 = 75%) switched to a different combination of antipsychotics. Of note, the 2 groups did not differ with respect to psychiatric symptoms or hospitalizations, but the monotherapy group lost 0.5 BMI units, whereas the polypharmacy group gained 0.28 BMI units.

The high success rate of a switch from antipsychotic polypharmacy to antipsychotic monotherapy in more than 2 out of 3 patients justifies an attempt of switching to monotherapy in most patients, provided that patients are closely monitored to make eventual use of the rescue option of returning to polypharmacy. On the other hand, at least one third of schizophrenic patients may not benefit from at least 1 monotherapy option that was part of their current polypharmacy regimen. For these persons, a trial with a different antipsychotic used in monotherapy and, especially, of clozapine should be attempted before accepting polypharmacy as the only option for adequate symptom control. Where augmentation of antipsychotic monotherapy with electroconvulsive therapy (ECT) or switch to long-term maintenance ECT would fit with such patients is still unclear.


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