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OBJECTIVE: Outcomes monitoring data in a large health care system were used to evaluate the effectiveness of atypical neuroleptic medications in actual clinical practice. METHOD: National administrative data from the Department of Veterans Affairs were used to identify patients with schizophrenia who had no change in antipsychotic medication over a 3-month index period in 1999 and for whom Global Assessment of Functioning Scale ratings were available from both the index period and the following year (N=9,066). Analysis of covariance, including potentially confounding factors, was used to compare change in functioning scores between patients who continued to take the same medication and those whose medication was switched during the follow-up year. Among patients whose medication was switched, change in functioning scores was compared by whether patients received a conventional neuroleptic or each of the four then available atypical neuroleptics after the medication switch. RESULTS: Patients who continued to take the same medication (N=7,157, 78.9%) had improved functioning scores from the index period to the follow-up year, while patients whose medication was switched (N=1,909, 21.1%) had declining functioning scores (mean change in scores of 0.6% and –3.7%, respectively). Among the patients whose medication was switched, no significant differences in functioning were found between patients grouped by the new type of medication received. CONCLUSIONS: In this large administrative database, patients with schizophrenia whose neuroleptic medication was switched showed significantly less improvement in Global Assessment of Functioning Scale scores than patients who continued to take their original medication. No significant differences in functioning scores were found for patients whose medication was switched to any of the atypical neuroleptics.