Effects of supraphysiological thyroxine administration in healthy controls and patients with depressive disorders

Background: Thyroxine (T4) in supraphysiological doses has been found to be an effective supplemental treatment in open studies for refractory mood disorders. Unexpectedly, only minimal side effects have been reported. The goal of the present study was to investigate whether healthy controls and depressed patients differ in their ability to tolerate supraphysiological doses of T4. Methods: This was an 8-week open study to investigate side effects and levels of thyroid hormones in 13 healthy controls and to compare results with those of 13 patients with refractory depression (unipolar and bipolar) undergoing the similar procedures and T4 dosing regimen in a previous augmentation study. Results: The rate of discontinuation due to side effects was significantly higher in the control group than for the patients (38% versus 0%). The severity of the side effects in the controls increased significantly during treatment with T4. The side effect scores of the patients were higher than those of the controls prior to T4 treatment, but did not change significantly during the treatment period. Although the serum concentrations of thyroid hormones rose significantly in both groups, concentrations of fT3 and fT4 were significantly higher in the controls. Conclusions: Healthy controls and depressed patients respond significantly differently to supraphysiological T4. Healthy controls experience higher elevations of thyroid hormones in response to supraphysiological T4, thus inducing significantly more side effects and discontinuation. Limitations: Open-label study; groups were studied at different times; in contrast to healthy controls, depressed patients were also taking antidepressants. Clinical relevance: Studies provide safety and tolerability data on treatment with supraphysiological doses of T4.