Adjunctive thyroid hormone treatment in rapid cycling bipolar disorder: A double‐blind placebo‐controlled trial of levothyroxine (L‐T 4 ) and triiodothyronine (T 3 )

Objectives This report describes the first comparative double‐blind, placebo‐controlled trial of levothyroxine (L‐T 4 ) and triiodothyronine (T 3 ) as adjunctive treatments in rapid cycling bipolar disorder. Methods Thirty‐two treatment‐resistant, rapid cycling patients who had failed a trial of lithium were randomized into three treatment arms: L‐T 4 , T 3 , or placebo. They were followed for ≥4 months with weekly clinical and endocrine assessments. Results There were no statistically significant differences between the groups in age, gender, duration of illness, or thyroid status. Markov chain analyses were employed to assess treatment effects on cycling patterns among mood states (euthymia, depression, mania, and mixed). Within groups , post‐treatment the L‐T 4 group spent significantly less time depressed or in a mixed state and greater time euthymic. The T 3 and placebo groups did not differ significantly pre‐ and post‐treatment in any mood state, although the pattern of effects was the same for the T 3 group as for the L‐T 4 group. Between groups , the L‐T 4 group had a significantly greater increase in time euthymic and decrease in time in the mixed state than the placebo group. Other group differences were not significant, although they were in the expected direction. Conclusions The findings in this first double‐blind study directly comparing the effects of L‐T 4 and T 3 therapy against placebo provide evidence for the benefit of adjunctive L‐T 4 in alleviating resistant depression, reducing time in mixed states and increasing time euthymic. Adjunctive T 3 did not show statistically significant evidence of benefit over placebo in reducing the time spent in disturbed mood states.