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Reviewing the Clinical Landscape
Published Online: 19 October 2018

Can Thyroid Elevations Settle the Bipolar Peaks and Valleys?

Rapid-cycling variants of bipolar disorder present an ongoing challenge to psychiatrists attempting to control the illness. Their patients’ mood episodes may jump from one polarity to another, making the efficacy of clinical interventions unclear and leaving patients exhausted from the constant shifts. For this reason, my attention turned quickly to an article by Walshaw et al. (1), recently published online in Bipolar Disorders. They studied the adjunctive use of supraphysiological doses of levothyroxine (T4) and triiodythyronine (T3) in lithium-resistant, euthyroid patients with rapid-cycling bipolar disorder.
Open-label studies of adjunctive supraphysiological thyroid hormone doses in the treatment of rapid-cycling bipolar disorder have been positive but considered preliminary because of concerns about placebo effects (2, 3). Walshaw et al.’s (1) article is noteworthy because of the authors’ efforts to discover whether similar findings can be seen in the setting of a placebo-controlled, double-blind trial. In addition, the authors attempted to discriminate between the efficacy of supraphysiological T4 and T3 by randomly assigning research participants to three treatment groups (T4, T3, or placebo). Most important, the authors focused on rapid-cycling patients, seeking to identify an effective treatment for this group of patients, who are often excluded from clinical trials.
The study concluded that supraphysiological T4 reduced the time patients spent depressed and in mixed states and increased euthymia, whereas T3 did not show any benefit over placebo. Side effects were minimal, and only one patient withdrew because of side effects. The most significant limitation to this study was the small sample size, which ranged from nine to 13 per group. This study should be replicated with more subjects enrolled but for now offers a novel, inexpensive, and relatively safe approach to treating patients who have rapid-cycling, lithium-resistant bipolar disorder.

References

1.
Walshaw PD, Gyulai L, Bauer M, et al: Adjunctive thyroid hormone treatment in rapid cycling bipolar disorder: a double-blind placebo-controlled trial of levothyroxine (L-T4 ) and triiodothyronine (T3 ). Bipolar Disord (Epub ahead of print, June 4, 2018)
2.
Bauer MS, Whybrow PC: Rapid cycling bipolar affective disorder. II. Treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study. Arch Gen Psychiatry 1990; 47:435–440
3.
Kelly T, Lieberman DZ: The use of triiodothyronine as an augmentation agent in treatment-resistant bipolar II and bipolar disorder NOS. J Affect Disord 2009; 116:222–226

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Published in print: Fall 2018
Published online: 19 October 2018

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Jeffrey J. Rakofsky, M.D.
Dr Rakofsky is with the Mood and Anxiety Disorders Program, Emory University School of Medicine, Atlanta.

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