Anticonvulsants in the Treatment of Major Depressive Disorder: An Overview

Major depressive disorder (MDD) is highly prevalent, potentially disabling, and sometimes fatal. Antidepressants (ADs) have improved its treatment, but incomplete response, sustained morbidity, recurrences, agitation, substance abuse, excess medical mortality, and suicide remain unsolved problems among mood disorder patients. AD treatment itself sometimes induces adverse behavioral responses. Several anticonvulsants (ACs) used to treat bipolar disorder (BPD) might also be of value for MDD. Accordingly, we reviewed published reports on ACs for MDD, identifying studies by computerized searches. We excluded reports dealing only with BPD patients or with sedatives, classified trials by design quality, and evaluated treatment of acute episodes and recurrences of adult MDD. We found 36 reports involving 41 relevant trials of carbamazepine (12 trials), valproate (11), lamotrigine (9), gabapentin (3), topiramate (3), phenytoin (2), and tiagabine (1). They include 9 blinded, controlled trials (of 28-70 days), involving carbamazepine (3 trials), lamotrigine (3), phenytoin (2), or topiramate (1) as primary treatments (5) or AD adjuncts (4). Some of these trials, as well as 7 of lesser quality, suggest benefits of carbamazepine, lamotrigine, and valproate, mainly as adjuncts to ADs. Another 20 anecdotes or small trials further suggest that these ACs might be useful as AD adjunctsspecifically to treat irritability or agitation in MDD. Overall, these reports provide suggestive evidence of beneficial effects of carbamazepine, lamotrigine, and valproate that require further study, especially for long-term adjunctive use, particularly in patients with recurring MDD with prominent irritability or agitation.