Thyroid hormone augmentation for bipolar disorder: a neurobiological and clinical narrative review

Bipolar disorder (BD) is a severe, chronic psychiatric illness defined by profound and recurrent fluctuations in mood, energy, and function. Treatment is generally limited by both the efficacy and safety of available agents. Thyroid augmentation has been found to be useful to treat depression and rapid cycling in BD. Herein, we provide a narrative review of adjunctive use of thyroid hormone in BD with a specific focus on its potential mechanism of action.

Ion dysregulation with mood-state-related reduced sodium pump activity and increased intracellular sodium and calcium are among the most reproduced biologic findings in manic and depressed bipolar patients. Thyroid hormone directly increases sodium pump expression and activity, and indirectly improves energy utilization in bipolar patients. Across the reviewed literature, approximately 300-350 patients received supraphysiologic doses of thyroid hormone (T3 or T4), with the majority comprising individuals with BD and yielding generally very positive outcomes and minimal harm. Thyroid hormone augmentation can improve depression and reduce rapid cycling, and while never studied to treat mania, it does not increase the risk of manic episodes in all of the studies. Inconsistencies in data are related to different dosing regimens in different studies.

Thyroid hormone appears to directly correct known pathophysiologic abnormalities in patients with bipolar disorder. While additional studies are needed to confirm these findings, sufficient data are available to warrant the use of supertherapeutic thyroid hormone augmentation in selected patients.