Introduction: This study was conducted to evaluate the effectiveness and safety of topiramate as add-on therapy for treatment-resistant bipolar disorder.
Methods: Twenty-one DSM-IV bipolar patients, considered resistant to treatment with lithium, carbamazepine or valproate, gave informed consent to receive increasing doses of the novel anticonvulsant topiramate as adjunctive therapy for their manic (n= 9), depressive (n= 6), hypomanic (n= 3), mixed (n= 2) or schizoaffective manic (n= 1) symptoms. The dosage of other mood stabilizer drugs remained unchanged throughout the 6-week follow-up. Outcome measures included the YMRS, HDRS-17, and CGI scales. Fifteen out of 21 patients completed the 6-week follow-up.
Results: Six patients (40% of completers, 29% by intention-to-treat) were considered responders to topiramate (> 50% reduction in YMRS or HDRS-17 and a decrease of 2 points in CGI). The drug was less effective in intially depressed patients. Topiramate was well tolerated and only one patient discontinued due to side-effects. The most common adverse effect was paresthesia (n= 2). Ten patients experienced moderate weight loss during the follow-up. The mean topiramate dose at endpoint was 158 mg/day.
Conclusions: These preliminary results suggest that topiramate may be a useful therapy for bipolar disorders, with promising results even in the most treatment-refractory patients.