Lamotrigine versus lithium augmentation of antidepressant therapy in treatment-resistant depression: efficacy and tolerability.

BACKGROUND Mood stabilizer augmentation of standard antidepressant drugs has been shown to be effective in treatment-resistant depression. Despite the reported high overall efficacy, lithium has been relatively underused in recent years. Lamotrigine, a novel anticonvulsant recently recognized as a mood stabilizer, seems to have putative antidepressive properties. The aim of the study was to investigate lamotrigine efficacy and tolerability as antidepressant augmentation for unipolar treatment-resistant depression compared to lithium. SUBJECTS AND METHODS 88 patients suffering from treatment-resistant Major depressive disorder, having acute recurrent depressive episodes according to DSM-IV criteria, were enrolled in the study. This was an open-label trial with a flexible dosing regimen. All patients, received antidepressants in full therapeutic doses. They were divided into two augmentation groups: 46 patients received 50-200 mg/day lamotrigine, and 42 patients received 600-1200 mg/day lithium. The Hamilton Rating Scale for Depression (HAM-D) and The Clinical Global Impression scale (CGI) were used to monitor therapeutic efficacy. Patients were evaluated weekly for an 8 week treatment period. RESULTS The HAM-D total score was significantly reduced in both treatment groups at the study endpoint, without any difference between the groups. However, significant clinical improvement was reached within the second treatment week in the lamotrigine group compared to the lithium group (p=0.01 vs. lithium). Lamotrigine showed significant efficacy on the HAM-D item 1(depressed mood; p=0.01), item 7 (work and interest; p=0.01) and CGI-Improvement scale (p=0.02). The drop-out rate due to treatment failure was lower in the lamotrigine group (n=1) compared to the lithium (n=4) group. Also, the incidence of side effects did not differ between the groups. CONCLUSIONS Our results suggest that lamotrigine could be useful as augmentation of antidepressants for treatment-resistant unipolar depression. Also, lamotrigine may accelerate the onset of antidepressant action, and therefore might be useful in treatment of major depression in general.