his study is examining the safety and effectiveness of two medications, ketamine and riluzole, in treating patients with treatment resistant major depressive disorder. This study will also examine the effectiveness of an FDA approved drug called lamotrigine in decreasing the potential side effects associated with ketamine.

This research proposal will investigate a glutamate-modulating agent, riluzole, in treatment-resistant patients who exhibit an acute, sustained response to a single dose of IV racemic ketamine. Fifty ketamine-responders will be randomized to riluzole or placebo in a 4-week, randomized, double-blind, continuation-phase study.

• Drug: Lamotrigine
• Drug: IV Ketamine
• Drug: Riluzole

Inclusion Criteria:

1. Male or female patients, 21- 70 years of age
2. Subjects have a history of at least one previous episode of depression prior to the current episode (recurrent major depressive disorder) or have chronic major depressive disorder (at least two years' duration)
3. Subjects have not responded to an adequate trial of one antidepressant in the current episode

Exclusion Criteria:

1. Female subjects who are either pregnant or nursing
2. Serious, unstable illnesses
3. Any previous use or treatment with ketamine, or riluzole
4. Past intolerance to lamotrigine, including drug rash