A nationwide nested case-control study of new-onset obsessive-compulsive disorder following antipsychotics use in schizophrenia

Objective A substantial proportion of patients with schizophrenia suffer from comorbid obsessive-compulsive disorder (OCD) possibly associated with antipsychotics. However, little is known about the comparative risks of the antipsychotics. The present study aimed to investigate the risk of new-onset OCD following the initiation of different antipsychotic medications for schizophrenia relative to haloperidol. Methods Using the Korean national claims data, patients aged 15-60 years newly diagnosed with schizophrenia between 2010 and 2018 were identified. Of the 47,808 patients with schizophrenia treated with nine commonly prescribed antipsychotics, 775 new-onset OCD patients were matched to 3,100 patients without OCD using nested case-control design with 1:4 case-control matching based on the sex, age of index date, date of schizophrenia diagnosis, observation period, locations of medical institutions, and level of medical facilities. Using multivariable conditional logistic regression analysis, odd ratios (ORs) for new-onset OCD comparing each antipsychotic agent relative to haloperidol were computed. Results The risk for new-onset OCD during treatment with clozapine was significantly higher than that with haloperidol (adjusted OR 2.86; 95% confidence interval [1.63-5.03]). The risks for new-onset OCD with other antipsychotics were not significantly different from that with haloperidol. In subgroup analysis, the early and intermediate, but not late-onset schizophrenia group showed significant risk for OCD associated with clozapine use. Conclusion The present findings, based on real-world national representative data, provide reliable evidence for the risk of new-onset OCD in patients with schizophrenia receiving clozapine at a population level.