Gabapentin in the Acute Treatment of Refractory Bipolar Disorder

Background: Gabapentin, a new anti-epileptic agent, has been anecdotally reported to be effective in the treatment of mania. We systematically assessed the response rate in bipolar patients being treated adjunctively with gabapentin for manic symptoms, depressive symptoms, or rapid cycling not responsive to standard treatments.

Method: Twenty-eight bipolar patients experiencing manic (n = 18), depressive (n = 5), or rapid-cycling (n = 5) symptoms inadequately responsive to at least one mood stabilizer were treated in an open fashion with adjunctive gabapentin. Illness response was assessed using the Clinical Global Impression Scale modified for bipolar disorder (CGI-BP). A 'positive response' was operationalized as a CGI response of much or very much improved.

Results: Fourteen of the 18 (78%) treated for hypomania or mania had a positive response to a dosage range of 600-3,600 mg/day. Patients with hypomania responded fastest, with a positive response achieved in 12.7 +/- 7.2 days. Patients with classic mania had a mean time to positive response of 25 +/- 12 days, and in patients with mixed mania it was 31.8 +/- 20.9 days. All of the five patients treated for depression had a positive response within 21 +/- 13.9 days. Only one of five patients with rapid cycling had a positive response. Gabapentin was well tolerated by all patients, with the most common side-effect being sedation.

Conclusions: Gabapentin appears to have acute anti-manic and anti-depressant properties as an adjunctive agent for refractory bipolar illness. Prospective double-blind studies are needed to further delineate its acute efficacy when used as monotherapy and its prophylactic efficacy as monotherapy or in conjuction with other mood stabilizers.