Does a combination regimen of thyroxine (T4) and 3,5,3′-triiodothyronine improve depressive symptoms better than T4 alone in patients with hypothyroidism?: Results of a double-blind, randomized, controlled trial

Some hypothyroid patients receiving levothyroxine replacement therapy complain of depressive symptoms despite normal TSH measurements. It is not known whether adding T-3 can reverse such symptoms. We randomized 40 individuals with depressive symptoms who were taking a stable dose of levothyroxine for treatment of hypothyroidism (excluding those who underwent thyroidectomy or radioactive iodine ablation of the thyroid) to receive T-4 plus placebo or the combination of T-4 plus T-3 in a double-blind manner for 15 wk. Participants receiving combination therapy had their prestudy dose of T-4 dropped by 50%, and T-3 was started at a dose of 12.5 mug, twice daily. T-4 and T-3 doses were adjusted to keep goal TSH concentrations within the normal range. Compared with the group taking T4 alone, the group taking both T-4 plus T-3 did not report any improvement in self-rated mood and well-being scores that included all subscales of the Symptom Check-List-90, the Comprehensive Epidemiological Screen for Depression, and the Multiple Outcome Study (P > 0.05 for all indexes). In conclusion, the current data do not support the routine use of combined T-3 and T-4 therapy in hypothyroid patients with depressive symptoms.