This study will evaluate the effectiveness of treatment with supplemental triiodothyronine (T3, Cytomel) and sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), in improving symptoms of major depressive disorder (MDD).

The primary hypothesis is that triiodothyronine (Cytomel) supplementation of the antidepressant sertraline (Zoloft) will result in a greater improvement in HAM-D scores compared to placebo in the treatment of Major Depressive Disorder (MDD).

The goals of this proposal are to examine the relationship between Major Depressive Disorder (MDD) and abnormalities of the hypothalamic pituitary thyroid (HPT) axis. This protocol will systematically examine the value of supplemental triiodothyronine (T3, Cytomel) with sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI) in the treatment of MDD. The focus will be on two overlapping populations: 1) those with evidence of HPT abnormalities, and 2) those who did not respond to a previous adequate SSRI trial

Inclusion Criteria:

• Male or female between the ages of 18 and 60. (The upper age is limited to 60 because thyroid changes, including blunting of the TSH response to TRH occurs with age and can potentially confound the relationship between the HPT axis and MDD.)
• Primary diagnosis of unipolar Major Depressive Disorder
• HAM-D (21 item) score >18

Exclusion Criteria:

• Alcohol abuse or alcohol dependence within the past year.
• Psychoactive substance abuse or dependence within the past year.
• Clinical evidence of severe Personality Disorder that would make study participation and completion unlikely.
• ECT within the past 6 months.
• Grade I hypothyroidism defined as low thyroid hormone levels with an associated elevated TSH; hyperthyroidism defined as elevated thyroid hormone concentrations with a low TSH.
• Serious and unstable medical illnesses.