Thyroid Hormone Treatment of Mood Disorders

Abstract

Both excess and insufficient thyroid hormones can lead to depression that is generally reversible with adequate thyroid treatment. On the other hand, major depression is associated with subtle chronobiological hypothalamic-pituitary-thyroid (HPT) axis dysregulation and thyroid hormones can be an effective adjunct to antidepressant treatment. However, the links between HPT axis status and efficacy of thyroid hormone supplementation in depression remain to be further clarified. While generally, depressed patients are chemically euthyroid, most exhibit a chronobiological HPT axis dysregulation (i.e., loss of the nocturnal thyrotropin [TSH] rise, blunted evening TSH response to protirelin [TRH], reduced difference in TSH response between 11 PM and 8 AM TRH tests [ΔΔTSH]), possibly associated with blunted 8 AM-TSH response to TRH and/or altered levels of circulating thyroxine (FT4) and triiodothyronine (T3). Usually, chronobiological HPT axis abnormalities are unrelated to increased cortisol levels. Normalization of thyroid function tests by antidepressants, especially the ΔΔTSH test, may occur before the clinical response. In patients who are resistant to antidepressants, there is good evidence for adjuvant therapy with thyroid hormones. While there is a limited evidence base to guide long-term adjunctive use, thyroid hormone augmentation can be a safe and effective alternative treatment for euthyroid-depressed patients who receive appropriate baseline and follow-up safety monitoring. However, it remains to be established which bio-clinical subtypes of depression respond preferentially to thyroid hormone supplementation. In the next future, metabolically stable TRH analogs could be used in order to maintain or restore homeostasis, which is frequently disrupted in depressive states.