Does Thyroid Supplementation Accelerate Tricyclic Antidepressant Response? A Review and Meta-Analysis of the Literature

Objective: The delayed onset of therapeutic response to antidepressants remains a major problem in the treatment of depression. Among the strategies to accelerate response to treatment, the early addition of thyroid hormone to antidepressants has been suggested as a viable method. The authors performed a meta-analysis of the literature on the use of thyroid hormone supplementation to accelerate the treatment of depression to determine whether there is sufficient evidence to support the clinical efficacy of this strategy. Method: Both a computer-aided search of the National Library of Medicine MEDLINE and an intensive search by hand were conducted to identify all double-blind, placebo-controlled studies assessing the concomitant administration of thyroid hormone and antidepressant to accelerate clinical response in patients with nonrefractory depression. Results: Six studies were identified. All were conducted with triiodothyronine ([T.sub.3]) and a tricyclic antidepressant. Five of the six studies found [T.sub.3] to be significantly more effective than placebo in accelerating clinical response. The pooled, weighted effect size index was 0.58, and the average effect was highly significant. Further, the effects of [T.sub.3] acceleration were greater as the percentage of women participating in the study increased. Conclusions: This meta-analysis supports the efficacy of [T.sub.3] in accelerating clinical response to tricyclic antidepressants in patients with nonrefractory depression. Furthermore, women may be more likely than men to benefit from this intervention. (Am J Psychiatry 2001; 158:1617-1622)