The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and perphenazine or between second-generation antipsychotics in people with schizophrenia.

Tardive dyskinesia rates for patients beginning treatment with conventional antipsychotics in their fifth decade or later are three to five times what has been found for younger patients, despite treatment with lower doses. Alternative treatments need to be investigated.

Objective This randomized trial addressed risks and benefits of staying on antipsychotic polypharmacy versus switching to monotherapy. Method Adult outpatients with schizophrenia taking two antipsychotics (127 participants across 19 sites) were randomly assigned to Stay on Polypharmacy or Switch to Monotherapy by discontinuing one antipsychotic. The trial lasted for 6 months, with a 6-month naturalistic follow-up. Kaplan-Meier and Cox regression analyses examined time to discontinuation of assigned antipsychotic treatment, and random regression models examined additional outcomes through time. Results Individuals assigned to Switch to Monotherapy had shorter times to all-cause treatment discontinuation than those assigned to Stay (p <.05). By month 6, 86% (n=48) of those assigned to Stay on Polypharmacy were still taking both medications whereas 69% (n=40) of those assigned to Switch to Monotherapy were still taking that monotherapy. Most monotherapy discontinuations entailed returning to the original polypharmacy. Groups did not differ with respect to psychiatric symptomatology or hospitalizations. The monotherapy group lost weight whereas the polypharmacy group gained weight. Conclusions Discontinuing one of two antipsychotics was followed by treatment discontinuation more often and more quickly than when both antipsychotics were continued. However, two thirds of participants successfully switched, groups did not differ with respect to symptom control, and switching to monotherapy resulted in weight loss. This supports the reasonableness of prescribing guidelines encouraging trials of antipsychotic monotherapy for individuals receiving antipsychotic polypharmacy, with the caveat that individuals should be free to return to polypharmacy if an adequate trial on antipsychotic monotherapy proves unsatisfactory.

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This article reviews eight published studies that describe clozapine's effects on TD and examines the outcome of 30 patients with TD treated with clozapine for up to 36 months. These data indicate that TD response to clozapine is variable but that approximately 43% of cases, particularly those with dystonic features, improved after clozapine treatment. Methodological limitations of the studies described, however, preclude definitive conclusions, which must await appropriately controlled trials.