Objective: This study investigates risks of developing diabetes mellitus (DM), hypertension, and hyperlipidemia in treating schizophrenia with first- and second-generation antipsychotics (FGA and SGA, respectively). Methods: We established two study sets, each consisting of patients with schizophrenia and without schizophrenia, from the insurance claims from 1997 to 2000. Study set I had 1631 patients taking FGA and 6524 non-schizophrenia controls; the other had 1224 patients taking SGA and 4896 controls. Controls were selected frequency matched with sex, age and the index year. All subjects were free of the studied metabolic disorders at the baseline. We measured incidences of these disorders developed by the end of 2008 in each cohort and their respective hazard ratios (HRs) for these disorders. Results: Schizophrenic patients taking FGA were older than those taking SGA. In the Cox models, significance adjusted HRs associated with SGA were 1.82 (95% confidence interval (CI) 1.30-2.55) for DM and 1.41 (95% CI 1.09-1.83) for hyperlipidemia. For those on the FGA, the risk was only significant in developing DM (HR 1.32, 95% CI 1.01-1.75). The age-specific antipsychotics-associated risks for metabolic disorders were higher in young patients than in older patients particularly for hypertension; the HRs in 10-19. years of age were 4.52 (95% CI 1.76-11.6) associated with FGA and 3.92 (95% CI 1.83-8.39) associated with SGA. Conclusions: Patients with schizophrenia on SGA have higher risk of developing metabolic disorders than those on FGA. It is likely that older patients have already gone through the age of developing these side-effects and were free of them at the baseline.
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