Immediate adjunctive Thyroid Hormone to enhance antidepressant effect?…. probably not

The Combination of Triiodothyronine (T3) and Sertraline is Not Superior to Sertraline Monotherapy in the Treatment of Major Depressive Disorder

Garlow SJ, Dunlop BW, Ninan PT, Nemeroff CB

J Psychiatr Res. 2012;46:1406-1413.

This is only ONE study. For more information and safety, the results should  be replicated
in an independent additional study, ideally more than one, and then a meta-analysis could be performed. Plus, this study is about the use of thyroid hormone as an adjunctive to the antidepressant in the very beginning, and not as an augmentation strategy in situations where the antidepressant alone did not work sufficiently. These two different situations should and cannot be directly compared to each other.

Study Summary

This was an 8-week, double-blind, randomized, placebo-controlled clinical trial of 153 adult outpatients with major depressive disorder. Treatment with triiodothyronine (T 3) plus sertraline was compared with sertraline monotherapy. Sertraline was flexibly adjusted according to patient tolerance, and the T 3 dose was increased during week 2 of the study. The mean final dosages were 144.7 mg/day for sertraline and 48.2 μg/day for T 3.

There was no difference between treatment groups at final assessment; 65% of patients who received placebo and 61.8% of T 3-treated patients achieved response. Response was defined as a 50% reduction in, or a total score of less than 15 on, the 21-item Hamilton Rating Scale for Depression (HRSD-21). Remission (HRSD-21 score less than 8) was achieved in 50.6% of the placebo group and 40.8% of T 3-treated patients. The median time to response did not differ between groups. Baseline thyroid function tests did not predict response to sertraline treatment or T 3 augmentation.


Garlow and colleagues concluded that their results do not support the routine use of T 3 to enhance or accelerate the onset of antidepressant response in patients with major depressive disorder. Moreover, numerically, the proportion of responders and remitters was higher for the adjunctive placebo group than for the adjunctive T 3 group (numbers needed to treat, 32 and 11, respectively, in favor of adjunctive placebo).

The investigators commented that the patients included in this study were not specifically treatment-resistant and were relatively early in the course of their disease and treatment. Therefore, the negative finding could in part be the result of the high overall responsiveness to selective serotonin reuptake inhibitor monotherapy in these patients. Thankfully, we do have effective agents approved by the US Food and Drug Administration to augment antidepressant treatment of major depressive disorder — extended-release quetiapine, aripiprazole, and combination olanzapine/fluoxetine.