Case reports of the reemergence of psychotic symptoms after conversion from brand-name clozapine to a generic formulation

Background. The use of generic drugs has resulted in, considerable cost sav ings; however, whether all generics are truly bioequivalent to their brand- name counterparts is questionable. Although the efficacy of clozapine in th e management of treatment-resistant schizophrenia has been well established , reports of relapse after conversion to a generic formulation are becoming more common. Objective: This article presents 7 case studies of patients in a long-term residential care facility who experienced a relapse of psychotic symptoms w hen the pharmacy inadvertently switched their therapy from brand-name cloza pine to a generic formulation. Neither patients, physicians, nor staff of t he facility were aware of this switch. Possible reasons for the apparent in creased risk of relapse in some patients switched to the generic formulatio n of clozapine are explored, with reference to US Food and Drug Administrat ion bioequivalence standards and reports. Results. All 7 patients, whose condition had been well stabilized with bran d-name clozapine, experienced a rapid and profound deterioration after the switch to the generic formulation. Five patients required hospitalization. All patients responded well when brand-name clozapine was reinstated. Conclusion: The findings suggest that brand-name clozapine and the generic formulation may display important clinical differences, and a comparable th erapeutic response may not be achievable despite adequate monitoring. Large , controlled, prospective trials are needed to clarify the potential for tr eatment failure with the use of generic clozapine.