Clinical experience using adjunctive gabapentin in treatment-resistant bipolar mixed states

Open studies and case observations have suggested that gabapentin may be ef fective in the treatment of bipolar disorder. However, the adjunctive use o f the drug in bipolar mixed states has not been specifically addressed befo re. Methods: Twenty-one patients with bipolar I mixed episodes as defined b y 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 leve ls of standard mood stabilizers, and had a mean clinical global impression (CGI) of 5.2 +/- 0.8 when entering the study. Gabapentin treatment was star ted 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 Rat ing Scale (YMRS), and CGI. Patients with final CGI scores of 1 or 2 were re garded as responders. Results: Only one patient had to interrupt the drug t reatment, due to irritability and ataxia. Negative interactions between gab apentin and concomitant psychotropic medications were not observed. The con dition deteriorated in only one patient (final CGl=5). Ten patients were re garded as responders: four showed marked improvement (CGl=1), and six had m oderate improvement (CGl=2). The mean dose of gabapentin at week 8 was 1130 mg (range 600-2000 mg). The mean final CGI score for all patients (respond ers and nonresponders combined) was 3.7+1.1 (the mean change in CGl was sig nificant, t = 6.1, P < 0001). The reduction in the mania score was minimal and statistically insignificant. However, the mean HRSD score showed a stat istically significant reduction from 18.2 to 10.6 (t = 5.73, P < 0.0001), i rrespective of the baseline severity of the mania. All but one of the respo nders maintained these therapeutic improvements over 4-12 months, in most c ases 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 symptomato logy.