Maximizing Schizophrenia Outcomes: How Important Is the Initial Selection of Antipsychotic Drug?

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Maximizing Schizophrenia Outcomes: How Important Is the Initial Selection of Antipsychotic Drug?

The most valuable message from this direct comparison of five antipsychotics might be that psychiatrists need to use a spectrum of strategies.

Efficacy trials have suggested the superiority of atypical antipsychotic drugs over older agents, but these trials have not been conducted under real-world conditions. In an 18-month, double-blind, randomized, multisite trial, researchers used minimal inclusion criteria to enroll 1493 patients with schizophrenia in a comparison study of the neuroleptic perphenazine and four newer antipsychotics: olanzapine, quetiapine, risperidone, and ziprasidone.

Olanzapine recipients were less likely than recipients of the other drugs to discontinue medication for any reason (64% vs. 74%–82%), and they continued treatment significantly longer as well (median, 9.2 months vs. 3.5–5.6 months). Secondary analyses of symptom-rating scales showed a similar trend, although olanzapine recipients were more likely to stop the drug due to adverse effects (especially weight gain and metabolic changes); considerable weight gain (>7% of baseline weight) occurred in 30% of olanzapine recipients and 7% to 16% of patients on other drugs. The five groups showed no differences in incidence of extrapyramidal side effects, although these triggered discontinuation most often in the perphenazine group (8%).

Comment: The somewhat greater effectiveness of olanzapine was counterbalanced by its lower tolerability and safety. The most striking finding, however, is that few patients maintained their drug assignments over the 18-month period. The researchers did not note how many patients had effective case management, although clinical practices commonly use this strategy to increase adherence to medications and maximize effectiveness: Case management might maximize outcomes more than the selection of any one particular agent. Also, the researchers did not report the effect of comorbid alcohol or drug abuse, which can lead to poor adherence in schizophrenic patients, particularly in the absence of good case management. Finally, the results suggest that a spectrum of medication options needs to be available because different agents obtain optimal response in different patients.

— Peter Roy-Byrne, MD

Published in Journal Watch Psychiatry October 5, 2005