Topiramate augmentation of clozapine in schizophrenia: a double-blind, placebo-controlled study

The persistence of psychotic, affective, cognitive, and psychosocial symptoms despite medications is commonly observed in schizophrenic patients. The present study was a 24-week double-blind, randomized, placebo-controlled trial aimed to explore the efficacy of topiramate add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of treatment-resistant schizophrenic patients receiving clozapine. After clinical and cognitive assessments were randomly allocated to receive either up to 200mg/ day of topiramate or a placebo. A final sample of 43 patients completed the study. The results obtained indicate that topiramate appeared to be scarcely effective for reducing clinical symptomatology in schizophrenic patients who have had an incomplete clinical response to clozapine. Regarding cognitive functioning, in our sample a trend to experience cognitive impairment in the examined domains was observed, as the patients included in the topiramate groups expressed cognitive complaints partially confirmed by a mild worsening of performances on certain cognitive tasks. Schizophrenia is a heterogeneous disorder with regard to pathophysiology; therefore, data reflecting the mean response of a sample of patients may fail to reveal therapeutic effects. More research is needed to better identify subgroups of patients with peculiar features which may account for responsivity to experimental medications and augmentation strategies.