Antimanic Efficacy of Topiramate in 11 Patients in an Open Trial With an On-Off-On Design

Background: A series of open studies suggeststhat topiramate has efficacy in bipolar disorder. To furtherinvestigate the potential value of topiramate as an antimanicagent, we conducted an open trial in 11 manic patients.

Method: Eleven patients with bipolar I disorderwith an acute manic episode (DSM-IV) were treated with a moodstabilizer and/or antipsychotics in sufficient and fixed doses.All had a Young Mania Rating Scale (YMRS) score of at least 24(mean ± SD = 33.5 ± 8.1). Topiramate was added after stableplasma levels of concomitant mood stabilizers had been reachedand was titrated within 1 week to a final dose in the range of 25to 200 mg/day, depending on clinical efficacy and tolerability.Topiramate was discontinued after 10 days, while concomitantmedication remained unchanged. After 5 days, topiramate wasreintroduced at similar or increased dosages for another 7 days.Patients were assessed with the YMRS; the Clinical GlobalImpressions scale version for bipolar patients; and the 21-itemHamilton Rating Scale for Depression.

Results: Seven of the 11 patientsinitially showed a good antimanic response with > 50%reduction in YMRS score. One patient showed psychotic featuresfollowing rapid increase in topiramate dosage and dropped out onday 10. After discontinuation of topiramate, 7 of the remaining10 patients worsened (increase of >= 25% in YMRS score), 2remained stable, and 1 discontinued follow-up after goodrecovery. After reintroducing topiramate, all patients improvedagain within a week, with 8 of 9 meeting the responder criterionof >= 50% YMRS score reduction when comparing baseline valueswith those of day 22. With the exception of the patient whodeveloped psychosis, topiramate was well tolerated. Concomitantmedication did not interfere with plasma levels of drug, exceptfor carbamazepine level in 1 patient.

Conclusion: The antimanic response amongpatients in this study appears reproducibly linked to theaddition of topiramate.