Thyroid Augmentation May Improve Depression in Women with Treatment-Resistant Bipolar Depression

September 12, 2011 · Posted in Potential Treatments 

WomanWe have previously written about a study of supra-physiological doses of levothyroxine (a synthetic version of the hormone T4 sold under the brand name Synthroid) performed by Mike Bauer and colleagues in Dresden, Germany and at UCLA. Sixty-three patients were initially treated with an antidepressant and/or a mood stabilizer for one week during a single-blind phase. Then the six-week double-blind phase of the study began, in which patients were given either adjunctive T4 (in the form of levothyroxine ) or placebo, and this was followed by an additional six weeks of open treatment with T4. Patients were started at 100mcg and increased on a weekly basis to 200 and then 300mcg/day.

Overall, T4 had no statistically significant effect that differentiated it from placebo, but among women, there was a significantly greater degree of improvement in the Hamilton Rating Scale for Depression scores for those on T4 (-42.4%) than for those on placebo (-16.6%), p= .018.

Editor’s note: This study is the first randomized, placebo-controlled trial of supra-physiological doses of T4. A small series of reports in the literature from several different investigative groups had previously suggested efficacy of this compound in rapid cycling and treatment-resistant patients.The supra-physiological doses of T4 used in this study are different from typical replacement doses of T3 or T4, which have often been used in adjunctive treatment of patients with unipolar and bipolar depression. T3 has been studied more than T4, and a meta-analysis of T3 augmentation (usually 25-50mcg/day) has shown positive effects over placebo. Those results suggest the potential utility of a trial with usual-dose T3 augmentation prior to treatment with supra-physiological doses of T4.

Even with the low or replacement doses of T3, it appeared that women were more likely to respond to the treatment than men were, so the potential gender differences in response to thyroid augmentation (both replacement T3 and supra-physiological T4 doses) deserve further investigation.

What is clear in both instances is that baseline thyroid function is not related to therapeutic response, i.e. antidepressant augmentation with thyroid does not depend upon a patient being hypothyroid at baseline. Some endocrinologists may not be aware that thyroid has antidepressant effects independent of its thyroid hormone effects, and may think thyroid hormone supplementation is unnecessary if a patient exhibits normal baseline thyroid indices.


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