New Drugs in the Treatment of Mood Disorders

The anticonvulsants carbamazepine (CBZ) and valproate (VPA) have efficacy in the treatment of mood disorders, suggesting that other anticonvulsants with related mechanisms of action may have similar utility. Additional treatments are sorely needed because many patients with recurrent affective disorder have symptoms refractory to treatment with conventional agents, including lithium, carbamazepine, and valproate. This refractory group is the major focus of our investigative efforts on 3-west in the Section of Psychobiology, NIMH. Moreover, establishing differential clinical and biological predictors of response has become increasingly important both to rapid allocation of appropriate treatment and as they may supply insight into the pathophysiology of the mood disorders and their subtypes. Lamotrigine, a phenyltriazine use-dependent sodium channel blocker that inhibits release of excitatory amino acids, is a new anticonvulsant with fewer side effects than older agents and was recently approved by the FDA as adjunctive therapy in the treatment of partial seizures. Heretofore, only preliminary open clinical evidence suggested that lamotrigine may have mood stabilizing properties. Gabapentin is a neutral amino acid and gamma-aminobutyric acid (GABA) analog which increases brain GABA levels and has fewer side effects than older agents and does not require hematological or hepatic monitoring. Preliminary evidence only from open "add-on" series had suggested that gabapentin therapy might have antidepressant and antianxiety effects, if not mood stabilizing properties. We wish to evaluate the efficacy of lamotrigine and gabapentin in the refractory mood disorders. We also wish to examine the neurobiology and phenomenology of lamotrigine and gabapentin responders and nonresponders to ascertain potential predictors and concomitants of response to these medications. This study may lead to improvement in the treatment and understanding of mood disorders by providing controlled data on efficacy of these potential new treatments, potential predictors of response, and further insights into the pathophysiology of mood disorders.