Preliminary observations on the effectiveness of levetiracetam in the open adjunctive treatment of refractory bipolar disorder

Objective: Levetiracetam is a recently approved, well-tolerated anticonvulsant with a unique mechanism of action yielding efficacy in treatment-refractory seizure disorders and positive effects in an animal model of mania. Given the effectiveness of a range of other anticonvulsants in bipolar disorder, we sought to evaluate levetiracetam in patients with treatment-resistant illness.

Method: Thirty-four patients received 500 to 1000 mg of levetiracetam titrated to a target dose of 2000 mg/day (maximum dose = 3000 mg/day) as open, adjunctive treatment for clinically significant symptoms of depression (N = 13), mania (N = 7), or cycling (N = 14) despite ongoing treatment with mood stabilizers. Inventory for Depressive Symptomatology-Clinician version (IDS-C), Young Mania Rating Scale (YMRS), and Clinical Global Impressions scale for use in Bipolar Illness ratings were completed at each visit for 8 weeks, and partial responders were offered continuation treatment. Data were collected from July 2001 to December 2002.

Results: Five of 16 (31%; 13 depressed, 3 cycling) patients with initial depressive symptoms met the criterion for remission (IDS-C score of: 13) at last observation. All of these patients were less severely ill at baseline, whereas none of those more severely depressed at baseline responded. The majority of the 16 patients (7 manic, 9 cycling) with manic symptoms at baseline showed improvement in the YMRS in the first 2 weeks. While 7 of the 16 (44%) patients met the criterion for manic response and remission at last observation, 4 showed intervening periods of moderate to marked exacerbation. Levetiracetam was weight neutral.

Conclusion: Other pilot trials should explore possible areas of psychotropic action of levetiracetam prior to the conduct of more controlled clinical trials.