Adjunctive thyroid hormone treatment in rapid cycling bipolar disorder: A double‐blind placebo‐controlled trial of levothyroxine (L‐T₄) and triiodothyronine (T₃)

Abstract

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

The association of serologically documented maternal thyroid conditions during pregnancy with bipolar disorder in offspring

“…For example, hypothyroxinemia contributes to altered triiodothyronine‐regulated gene expression in the fetus, which is involved in neuronal and microglial migration, phagocytosis, and astrocyte and oligodendrocyte differentiation . Triiodothyronine has also recently been used as an adjunctive treatment for bipolar disorder . Lastly, if replicated, our findings could offer potential preventive measures including the possibility of supplementing pregnant hypothyroxinemic mothers with thyroid hormone.…”

Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms

“…While triiodothyronine (T3) demonstrated to be effective and safe in the treatment of affective disorders (Kelly and Lieberman 2009), the use of higher than normal, supplementary doses of levothyroxine (L-T4) has shown promise in several open-label studies, including for patients with rapid cycling (Bauer and Whybrow 1990), prophylaxis-resistance (Baumgartner et al 1994; Bauer et al 2002b), and with acute refractory uni- or bipolar depression (Bauer et al 1998, 2002a, 2005). These beneficial findings have been confirmed more recently in placebo-controlled studies (Stamm et al 2014; Bauer et al 2016; Walshaw et al 2018): in the multicenter placebo-controlled study of Stamm et al (2014), supraphysiologic doses of L-T4 were added to continuing treatment with mood stabilizer and/or antidepressant medication in 62 patients with bipolar depression. After 4 weeks but not at the study end at week 6 HAMD scores in the L-T4 group were significantly lower compared to the placebo group.…”

“…Adjunctive treatment with supraphysiologic doses of L-T4 produced a significant decline in depression scores during the 6-week treatment, which was paralleled by restoration of metabolic activity in brain regions that are critically involved in the regulation of emotional processing and homeostasis. Recently, Walshaw et al (2018) found that mood-stabilizing effects of adjunctive treatment with supraphysiologic doses of L-T4 were significantly higher compared to effects of T3 and placebo in 32 patients with treatment resistant rapid cycling.…”

Diagnosing and treating major depressive episodes that lie along the mood disorders spectrum: focus on depression with mixed features

“…In a randomized, placebo-controlled trial of levothyroxine vs triiodothyronine in 32 patients with lithiumresistant rapid-cycling bipolar disorder, levothyroxine recipients spent significantly less time in a depressed or mixed state and more time euthymic than triiodothyronine recepients. 67 Compared to placebo recipients, levothyroxine recipients had increased time euthymic and decreased time in a mixed state.…”