Levothyroxine improves depression by modulating limbic function

By Will Boggs MD

NEW YORK (Reuters Health) - In bipolar disorder, levothyroxine improves depressive symptoms by modulating the function of the anterior limbic network, according to a PET study.

"Thyroid hormone does have a significant impact on brain activity in those brain areas that are considered to play a major role in the pathophysiology of depression," Dr. Michael Bauer, from University Hospital Carl Gustav Carus and Technische Universität Dresden in Germany, told Reuters Health by email.

Supraphysiologic doses of levothyroxine have shown promise for treating bipolar depression, but the mechanisms underlying the clinical improvement are unknown.

Encouraged by an earlier pilot study, Dr. Bauer's team assessed cerebral glucose metabolism with PET and 18-fluorodeoxyglucose (FDG) before and after six weeks of levothyroxine treatment in a placebo-controlled trial of 25 euthyroid patients. The patients had bipolar depression and had failed a course of treatment with a mood stabilizer and/or antidepressant.

Treatment with levothyroxine brought significant improvements in depression, compared with placebo treatment, they reported online January 20 in Molecular Psychiatry.

In the levothyroxine group, relative activity in the left thalamus, left dorsal striatum, and midline subgenual cingulate decreased as depressive symptoms improved. In contrast, there were no correlations between depressive symptoms and activity change in the placebo group.

Previous studies have shown abnormally high glucose metabolism in the thalamus and ventral striatum of depressed bipolar patients, which normalized after effective treatment with levothyroxine.

Dr. Bauer recommended, "If patients have normal thyroid levels (euthyroid), start with 100 mcg/d; after seven days increase to 200 mcg; and after another seven days titrate up to 300 mcg/d. Important: wait and see effects for at least five weeks (levothyroxine has a long half life, it needs some time to work)."

Levothyroxine is not approved for the treatment of depression, however.

And Dr. Bauer warns that the treatment is not for everyone. He emphasized the importance of "careful selection of patients with bipolar depression: use it in refractory patients only; carefully exclude those with a current or history of heart disease."

SOURCE: http://bit.ly/1zCKmxe

Molecular Psychiatry 2015.

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