۱- Introduction

۲- Methods

۳- Discussion

References

Abstract

Treatment-resistant depression (TRD) is a growing problem in psychiatric practice with some 15–۲۰% 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.

Background

Major Depressive Disorder (MDD) is a common psychiatric condition that impacts as many as 16% of Americans [1]. While many patients never enter into treatment, the outcome of many that do is frequently suboptimal [2]. Patients who receive treatment and continue to have residual symptoms are at a high risk of having a recurrence, and as many as 50% of treated patients will continue to have residual symptoms [2–۴]. Additionally, patients who do respond and experience a recurrence may go on to develop chronic depressive symptoms that are unresponsive to further antidepressant manipulations [5,6]. Treatment-resistant depression (TRD) is a growing problem in psychiatric care with up to 15–۲۰% of depressed patients becoming chronically depressed [7–۹] and perhaps as many as 40% in tertiary settings [10]. Furthermore, TRD appears to be increasing faster than generational time [11,12]. TRD has been variously defined as failure to respond to 1 trial of antidepressant monotherapy, failure to respond to 2 or more trials of monotherapy with different antidepressants, or failure to respond to 4 or more trials of different antidepressant therapies, including augmentation, combination, and electroconvulsive therapy (ECT) [5]. The cause of TRD is still poorly understood, and the majority of clinicians believe it is simply a form of severe depressive illness. However, the changing prevalence of TRD, and its apparent expansion in association with the expanding use of antidepressants has led to the idea that antidepressants may have a paradoxical effect [13]. Several groups have championed the idea that TRD may be attributed to the long-term treatment with antidepressant drugs (AD) [11,13–۱۵]. Understanding the potential mechanism of this hypothesized phenomenon may be explained by the short form of the serotonin transporter (5HTTR) [9].