Clinical effects of a randomized switch of patients from Clozaril to generic Clozapine

Introduction: Clozapine was discovered in 1959 but withheld from the United States market after several deaths due to agranulocytosis. The medication was approved in the United States in 1989 on a compassionate-use basis and was first marketed in 1990 as Clozaril. In 1999, following approval by the U.S. Food and Drug Administration, Zenith Goldline Pharmaceuticals (ZGP) introduced a generic form of clozapine. Method: After 5 weeks of data collection (phase I), 24 patients were randomly assigned to group A and 21 patients to group B. Patients had DSM-IV diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder with psychosis, or atypical psychosis with mood disorder. In phase II, group A received a mean daily dose of 630 mg of generic clozapine, and group B continued to receive Clozaril at a mean daily dose of 610 mg, each for 8 weeks. In phase III, group A was reassigned to Clozaril, and group B was switched to generic clozapine, each for 8 weeks. At the end of phase III, group B resumed Clozaril. Efficacy was measured with the Clinical Global Impressions-Improvement (CGI-I) scale, the Brief Psychiatric Rating Scale (BPRS), and the Beck Depression Inventory (BDI). Results: Five patients experienced relapse when they were switched from Clozaril to generic clozapine. Eleven patients worsened short of full relapse, 9 while receiving ZGP generic clozapine and 2 while receiving Clozaril. CGI-I scores and BPRS scores favored patients receiving Clozaril significantly. Only BDI scores favored patients receiving generic clozapine significantly. Conclusion: Until more studies have been performed, clinicians and administrators should carefully monitor stable Clozaril-treated patients who are being switched to generic clozapine.