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 T3 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 T4 plus placebo or the combination of T4 plus T3 in a double-blind manner for 15 wk. Participants receiving combination therapy had their prestudy dose of T4 dropped by 50%, and T3 was started at a dose of 12.5 μg, twice daily. T4 and T3 doses were adjusted to keep goal TSH concentrations within the normal range. Compared with the group taking T4 alone, the group taking both T4 plus T3 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 T3 and T4 therapy in hypothyroid patients with depressive symptoms.