Topiramate in schizophrenia: a review of effects on psychopathology and metabolic parameters

Less than half of patients with schizophrenia obtain full response to antipsychotic drugs and, while clozapine represents the treatment of choice for refractory psychosis, a significant number of individuals remain only partially responsive. Despite a need for augmentation in this subpopulation, to date clear choices have not been forthcoming. Because clozapine, along with the majority of second-generation agents (SGAs), are linked to metabolic disturbances, augmentation strategies that do not further exacerbate these side effects are needed. Topiramate, unlike other anticonvulsants used for augmentation purposes, has been associated with weight loss. This article reviews the safety and efficacy of topiramate in treatment-refractory schizophrenia, including effects on metabolic disturbances, which burden this population. While current evidence specifically examining improvements in psychopathology demonstrates small to moderate benefits with topiramate augmentation, a growing body of evidence suggests that topiramate may have beneficial effects on antipsychotic-induced weight gain. We conclude that topiramate's metabolic profile, taken together with a current lack of evidence supporting a particular augmentation strategy, argues for further well-controlled studies examining its potential as an augmentation strategy in schizophrenia.