Antimanic efficacy of topiramate in 11 patients in an open trial with an on-off-on design

Background: A series of open studies suggests that topiramate has efficacy in bipolar disorder. To further investigate the potential value of topirama te as an antimanic agent, we conducted an open trial in 11 manic patients. Method: Eleven patients with bipolar I disorder with an acute manic episode (DSM-IV) were treated with a mood stabilizer and/or antipsychotics in suff icient and fixed doses. All had a Young Mania Rating Scale (YMRS) score of at least 21 (mean +/- SD = 33.5 +/- 8.1). Topiramate was added after stable plasma levels of concomitant mood stabilizers had been reached and was tit rated within I week to a final dose in the range of 25 to 200 mg/day, depen ding on clinical efficacy and tolerability. Topiramate was discontinued aft er 10 days, while concomitant medication remained unchanged. After 5 days, topiramate was reintroduced at similar or increased dosages for another 7 d ays. Patients were assessed with the YMRS; the Clinical Global Impressions scale version for bipolar patients; and the 21-item Hamilton Rating Scale f or Depression. Results: Seven of the 11 patients initially showed a good antimanic respons e with > 50% reduction in YMRS score. One patient showed psychotic features following rapid increase in topiramate dosage and dropped out on day 10. A fter discontinuation of topiramate, 7 of the remaining 10 patients worsened (increase of greater than or equal to 25% in YMRS score), 2 remained stabl e, and 1 discontinued follow-up after good recovery. After reintroducing to piramate. all patients improved again within a week, with a of 9 meeting th e responder criterion of greater than or equal to 50% YMRS score reduction when comparing baseline values with those of day 22. With the exception of the patient who developed psychosis, topiramate was well tolerated. Concomi tant medication did not interfere with plasma levels of drug, except for ca rbamazepine level in 1 patient. Conclusion: The antimanic response among patients in this study appears rep roducibly linked to the addition of topiramate.