Metabolic implications of low-dose triiodothyronine administration in rats: relevance to the adjunctive use of triiodothyronine in the treatment of depression.

The adjunctive use of triiodothyronine (T3) with tricyclic antidepressants is generally believed to augment the efficacy of the tricyclic medications in unipolar, bipolar, and treatment-resistant depression. In the small subset of depressed patients with evidence for overt or subclinical hypothyroidism, the efficacy of supplementary T3 is logically presumed to derive from the amelioration of the hypothyroidism. It is, however, uncertain why adjunctive T3 therapy is often effective in the initially euthyroid depressed patient and if such therapy induces subclinical hyperthyroidism. To determine the metabolic state induced by low-dose T3 treatment, rats were administered nonpulsatile, submaintenance doses of T3 to achieve marked but incomplete suppression of the serum thyroxine (T4) (to 25%-50% of control levels) and serum thyrotropin (TSH) concentrations over a 10-week interval. No statistically significant change in the serum T3 was observed. At sacrifice, multiple parameters of peripheral metabolic status (growth rate, heart rate, organ weights, and tissue alpha-glycerophosphate dehydrogenase activities) in cerebrum, liver, kidney, spleen, and testes were consistent with euthyroidism. Thus, in a centrally regulated T3-predominant environment such as accompanies treatment with submaintenance doses of T3, originally euthyroid animals appear to remain in a euthyroid metabolic state.