Levothyroxine Shows Efficacy in Rapid Cycling Bipolar Disorder

Pills Spilling Out Of Bottle
Pills Spilling Out Of Bottle
Investigators examined levothyroxine and triiodothyronine as adjunctive treatment therapy for patients with rapid cycling bipolar disorder.

Adjunctive levothyroxine (L-T4) has shown efficacy in mitigating treatment-resistant depression, decreasing the time spent in mixed states, and increasing the amount of time spent in a normal mood state, according to a study recently published in Bipolar Disorders

This study included 32 individuals with treatment-resistant, rapid cycling bipolar disorder who had not had success with a lithium trial. After random assignment into L-T4, triiodothyronine (T3), or a placebo control group, the study researchers performed weekly endocrine and clinical assessments for a follow-up period of at least 4 months. Sex, age, length of illness, and thyroid status were statistically similar across all 3 groups. The study researchers used Markov chain analyses to evaluate the effects of treatments on mood state cycling, including depression, mania, euthymia, and mixed.

After treatment, those treated with L-T4 experienced more time euthymic (+33.1%, P = .022) and less time in a depressed state (−18.1%, P = .022) or mixed mood state (−13.3%, P = .031). Participants given T3 or placebo showed no significant change from baseline for any mood state, though the T3 group showed an identical effects pattern as L-T4. Compared with the placebo group, the L-T4 group showed significant improvements in increased time euthymic (+33.1% vs −6.5%, P = .033) and decreased time in mixed mood states (−13.3% vs +9.3%, P = .045). Differences between other groups were non-significant but followed the expected directionality.

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The study researchers conclude that “[the] findings in this first double-blind study directly comparing the effects of L-T4 and T3 therapy against placebo provide evidence for the benefit of adjunctive L-T4 in alleviating resistant depression, reducing time in mixed states and increasing time euthymic. Adjunctive T3 did not show statistically significant evidence of benefit over placebo in reducing the time spent in disturbed mood states.”


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) [published online June 4, 2018]. Bipolar Disord. doi: 10.1111/bdi.12657