For this proposed study, the modified design begins with adolescents with major depressive disorder who have not responded to a trial of a selective serotonin reuptake inhibitor antidepressant (SSRI), fluoxetine, of adequate dose and duration, and randomizes them either to a second SSRI or to fluoxetine augmented by lamotrigine. Non-responders to 8 weeks of fluoxetine, on at least 40 mg/day, who have not had to discontinue fluoxetine because of adverse effects, would be randomized to: (A) continue fluoxetine with lamotrigine augmentation, for 8 weeks, as in the active arm of the original Stage 2, or (B) discontinue fluoxetine and begin a second SSRI, for 8 weeks. We will use sertraline as the second SSRI, because of the data supporting efficacy from the randomized placebo-controlled trial by Wagner, et.al. (JAMA, '03). Citalopram is also a possibility (Wagner et.al, Am J. Psychiatry '04), but it has been in use for a shorter period of time than sertraline.