Clinical Experience Using Adjunctive Gabapentin in Treatment-Resistant Bipolar Mixed States

Abstract

Objective: Open studies and case observations have suggested that gabapentin may be effective in the treatment of bipolar disorder. However, the adjunctive use of the drug in bipolar mixed states has not been specifically addressed before. Methods: Twenty-one patients with bipolar I mixed episodes as defined by Diagnostic and Statistical Manual of Mental Disorders (Revised) (DSM-III-R), who were admitted to the outpatient department at the Psychiatry Clinic of the University of Pisa, were treated adjunctively with gabapentin for a period of eight weeks. All patients had been resistant to therapeutic levels of standard mood stabilizers, and had a mean clinical global impression (CGI) of 5.2 ± 0.8 when entering the study. Gabapentin treatment was started at 300 mg/ day and increased up to 2000 mg/day. Patients were evaluated using the Hamilton Rating Scale for Depression (HRSD), the Young Mania Rating Scale (YMRS), and CGI. Patients with final CGI scores of 1 or 2 were regarded as responders. Results: Only one patient had to interrupt the drug treatment, due to irritability and ataxia. Negative interactions between gabapentin and concomitant psychotropic medications were not observed. The condition deteriorated in only one patient (final CGI = 5). Ten patients were regarded as responders: four showed marked improvement (CGI = 1), and six had moderate improvement (CGI = 2). The mean dose of gabapentin at week 8 was 1130 mg (range 600 - 2000 mg). The mean final CGI score for all patients (responders and nonresponders combined) was 3.7 ± 1.1 (the mean change in CGI was significant, t = 6.1, P < 0001). The reduction in the mania score was minimal and statistically insignificant. However, the mean HRSD score showed a statistically significant reduction from 18.2 to 10.6 (t = 5.73, P < 0.0001), irrespective of the baseline severity of the mania. All but one of the responders maintained these therapeutic improvements over 4-12 months, in most cases requiring less concomitant antidepressant and neuroleptic medications. Conclusions: These results show that gabapentin appears to be potentially useful in the adjunctive treatment of drug-resistant bipolar mixed states, and that it was particularly effective in relation to depressive symptomatology.