Antidepressant discontinuation in treatment resistant depression

Treatment-resistant depression (TRD) is a growing problem in psychiatric practice with some 15-20% of depressed patients becoming chronically depressed and perhaps as many as 40% in tertiary settings. Several groups have championed the idea that TRD may be attributed to the long-term treatment with antidepressant drugs (AD). Subjects with the short form of the serotonin transporter gene (both heterozygotes and homozygotes) have an increased risk for depression in the setting of adversity compared to people with the long form. Moreover, these same individuals have a reduced likelihood of responding well to antidepressants, with reports of no response, delayed response, and increased side effects. This hypothesis needs to be examined in a randomized clinical trial. The study will examine the effect of discontinuation versus continuation of serotonergic antidepressants on disease progression in patients with treatment resistant depression. We will recruit 30 subjects and assess the depressive symptoms and disease progression. Genetic testing will be performed to optimize clinical outcome in both groups, but will also be used to evaluate if the short form of the serotonin transporter predicts disease progression and long-term antidepressant treatment response.