Effect of Topiramate Augmentation in Chronic Schizophrenia: A Placebo-Controlled Trial

Background: The limitations of antipsychotics for treatment of schizophrenia have led to investigation of the usefulness of pharmacological augmentation strategies. Clinical studies have provided evidence for glutamate abnormalities in schizophrenia. Topiramate is an anticonvulsant drug with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist properties; therefore, the objective of the present study was to explore the therapeutic efcacy of topiramate as an adjunctive medication in schizophrenia. Methods: A 17 week, double-blind, placebo-controlled clinical trial was performed on 80 patients (25 – 65 years) from 2005 – 2007. All were hospitalized in Mashhad psychiatric hospitals with chronic DSM-IV-TR-diagnosed schizophrenia. All participants received up to 300 mg/day of clozapine. In addition, participants randomly received either topiramate (200 – 300 mg/day) or placebo gradually added to their ongoing treatment. Efcacy of medication was measured by administering Positive and Negative Syndrome Scale at baseline and weeks 4, 8, 12, and 17. Results: During the study, 5 patients from the placebo group and 12 participants from topiramate group were excluded. Clozapine and topiramate group showed signicant decreases in all three subscales of PANSS values from baseline, with the maximum efcacy in week 12. However, after tapering topiramate, the general psychopathology sign was the only subscale that showed a signicant difference. The clozapine and placebo group showed a signicant decrease in all three subscales of PANSS values compared to baseline. The signicant efcacy for all subscales was obtained at the end point. No signicant differences in PANSS scores from baseline to end point were noted between case and control groups. Conclusion: Augmentation of clozapine and topiramate did not signicantly decline patterns in any of the three subscales of PANSS compared to the clozapine and placebo group. Irct ID: IRCT138904014236N1