We conclude that the superior efficacy of antidepressants over placebo can be demonstrated.

Significantly greater 5-HTT blockade at high dose provides a rationale for raising the dose from the minimum therapeutic dose in specific clinical circumstances. It is likely that 15% unoccupied 5-HTT remains, which should be addressed in future drug development.

The use of thyroid hormones in the treatment of depression is reviewed. The studies examining the use of triodothyronine (T3) alone as well as combination with antidepressants are discussed. The data suggest that there is little evidence that T3 alone has antidepressant efficacy but that this hormone may be used to enhance therapeutic effects of antidepressants in treatment refractory depressed patients. The different theories to explain the antidepressant effects of T3 are summarized.

There may be no advantage to a combination of these augmenting agents, although we failed to show separation between active treatments and placebo.