INTRODUCTION: Adjunctive treatment with supraphysiological doses of levothyroxine (L-T4) in bipolar depression shows promise, but the neurobiological mechanisms underlying clinical improvement are unknown. It has been postulated from animal studies that exogenous thyroid hormones may exert their modulatory effects in patients with affective disorders via an increase in serotonergic neurotransmission. Therefore, we investigated the loudness dependence of auditory evoked potentials (LDAEP) as a measure of central serotonergic activity and response to L-T4.

METHODS: This 6-week, double-blind, randomized, placebo-controlled study assessed the efficacy of L-T4 adjunctive to continuing treatment with mood stabilizer and/or antidepressant medication in 20 patients with bipolar depression. LDAEP was assessed before and after treatment with L-T4.

RESULTS: Scores of the Hamilton Depression Rating Scale and Montgomery Asberg Depression Rating Scale decreased significantly during the study. There was no difference in pre- and post-treatment LDAEP between the groups, and no correlation between LDAEP and psychometric measures in the course of the study.

DISCUSSION: The hypothesis of a relationship between response of augmentation therapy with levothyroxine in bipolar depression and serotonergic activity could not be confirmed.