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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.

Synopsis Drug-induced movement disorders have dramatically declined with the widespread use of second generation antipsychotics but remain important in clinical practice and for understanding antipsychotic pharmacology. The diagnosis and management of dystonia, parkinsonism, akathisia, catatonia, neuroleptic malignant syndrome and tardive dyskinesia are reviewed in relation to the decreased liability of the second generation antipsychotics contrasted with evidence from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial. Data from the CATIE trial imply that advantages of second generation antipsychotics in significantly reducing extrapyramidal side effects compared with haloperidol may be diminished when compared with modest doses of lower-potency first generation drugs, that the dichotomy between first and second generation drugs may be oversimplified, and that antipsychotics could be conceptualized as a single drug class with a spectrum of risk for movement disorders depending upon receptor binding affinities and individual patient susceptibility.

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.

These diagnostic criteria significantly advance the field because they represent the consensus of an international multispecialty expert panel, include critical values, provide guidance regarding the relative importance of individual elements, and are less influenced by particular theoretical biases than most previously published criteria. They require validation before being applied in clinical settings.

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