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Use of Antipsychotics and Risk of Cerebrovascular Events in Schizophrenic Patients: A Nested Case-Control Study

ObjectiveThis nested case-control study assessed the association between antipsychotic use and cerebrovascular adverse events among schizophrenic patients. MethodsUsing Taiwan’s National Health Insurance Research Database, we identified 9715 newly diagnosed schizophrenic patients during 2001 to 2009. Within the schizophrenic cohort, 386 cases of cerebrovascular events and 772 matched control subjects (1:2 ratio) were further identified. Conditional logistic regression models were used to examine the association between the use of antipsychotics (timing, duration, and type) and risk of cerebrovascular events. ResultsCurrent users of antipsychotics were associated with a 2-fold risk of stroke (adjusted odds ratio [OR], 1.94; 95% confidence interval [CI], 1.11–1.39; P = 0.02) as compared with nonusers. Among current users, patients who used antipsychotics less than 15 days (adjusted OR, 9.41; 95% CI, 3.08–28.71; P < 0.01) and 16 to 30 days (adjusted OR, 6.90; 95% CI, 1.09–43.69; P = 0.04) were associated with an extremely high risk of stroke. The risk of stroke was greater for patients who used first-generation antipsychotics alone or combination of first- and second-generation antipsychotics, with adjusted ORs of 2.75 (95% CI, 1.34–5.64; P < 0.01) and 2.37 (95% CI, 1.20–4.68; P = 0.01), respectively, but not in patients who used second-generation antipsychotic alone. ConclusionsThis population-based study extends previous evidence by documenting the increased cerebrovascular events associated with antipsychotic use in a schizophrenic cohort. A temporal association of such risk was reported in our study. Further studies are needed to assess the risk-benefit profile of first- and second-generation antipsychotics in this patient population.