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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

Department of Medicine and Division of Endocrinology and Metabolism, McMaster University (A.M.S., H.C.G., M.J.M., G.M.M.); Department of Medicine (A.M.S.) and Department of Psychiatry and Behavioral Neurosciences, Mood Disorders Program (M.J.M., G.M.M.), St. Joseph’s Healthcare; and Department of Medicine, Hamilton Health Sciences (H.C.G.), Hamilton, Ontario, Canada L8N 3Z5; and Department of Psychiatry, University of Medicine and Dentistry of New Jersey-New Jersey Medical School (R.T.J.), Newark, New Jersey 07103-2714

Address all correspondence and requests for reprints to: H. C. Gerstein, M.D., Department of Medicine, McMaster University, Room HSC 3V38, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. E-mail: gerstein{at}mcmaster.ca.

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.

Dr. Gerstein holds the Population Health Institute Chair in Diabetes Research (Sponsored by Aventis).

Abbreviations: CES-D, Comprehensive Epidemiological Screens for Depression; MOS, Medical Outcomes Study.

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