• treatment outcome defined categorically as Remission: A Hamilton Depression Scale (HAM-D) less or equal to 6.
  

• RESPONSE: Based on Hamilton Depression Scale (HAM-D)reduction of >50% from baseline to endpoint..
  
• REMISSION: Based on the other rating scales applied in this project.
  
• RESPONSE: Based on the other rating scales applied in this project.
  

The lifetime risk for major depressive disorder (MDD) is 15% in the general population. Current treatment approaches emphasize the achievement of remission. Remission implies virtual absence of depressive symptoms and is associated with better function and a better overall prognosis than response, which is usually defined as a 50% reduction in symptom severity. Sixty percent or more of patients treated optimally with antidepressants remain un-remitted and will need additional treatment. A potentially effective but under-exploited strategy to augment antidepressant effects is concurrent administration of the thyroid hormone, triiodothyronine (T3). We previously demonstrated the clinical efficacy and safety of T3 administered concurrently with the SSRI, sertraline, in the context of a randomized, double-blind placebo-controlled trial. Although all the patients were euthyroid, remission rates were significantly higher in the sertraline plus T3 group and were associated with significantly lower baseline T3 values and a significant decrease in serum thyroid stimulating hormone (TSH) values during the course of treatment.

The study aims to:

• Delineate a sub-population of depressed patients treated with sertraline, who are more likely to respond to T3 augmentation on the basis of thyroid function and genetic variation in thyroid pathway genes.
• Investigate the appropriate timing for the addition of T3.
• Assess the efficacy of reboxetine, a specific noradrenaline reuptake inhibitor, as a further supplement to the treatment of un-remitted patients. The results of this study could have a significant, direct clinical impact on the pharmacological treatment of MDD.