An Open Study of Triiodothyronine Augmentation of Tricyclic Antidepressants in Inpatients with Refractory Depression

Abstract

Several studies, mainly performed in outpatients, suggest that triiodothyronine (T3) addition may convert depressed patients who are nonresponders to tricyclic antidepressants (TCAs) into responders. This study is to our knowledge the first study of T3 augmentation performed in severely depressed inpatients. In our study no evidence for the efficacy of adjunctive T3 treatment was found in a sample of 14 inpatients. T3 augmentation was performed over a four-week period; during the last three weeks the daily dosage was 37.5 micrograms. The patients involved were suffering from refactory depression and previously had not responded to an adequate six-week course of treatment with a TCA (mainly nortriptyline). Many of the patients were suffering from depression with melancholic and/or psychotic features. During follow-up, eleven of the patients responded to further treatment with either an MAOI or electroconvulsive therapy.

Does Thyroid Supplementation Accelerate Tricyclic Antidepressant Response? A Review and Meta-Analysis of the Literature

“…Since then, two types of studies have been reported in the literature: 1) studies of acceleration strategies, which assess whether thyroid hormones prescribed initially with antidepressants speed the time for response to antidepressants in depressed subjects, and 2) studies of augmentation strategies, which assess whether thyroid supplementation added to treatment after a partial or minimal antidepressant response can potentiate the therapeutic response. The usefulness of thyroid augmentation for the treatment of a partial response or nonresponse to antidepressants has been assessed repeatedly over the past two decades (10)(11)(12)(13)(14)(15), culminating in the positive meta-analysis by Aronson et al (16). In contrast, the potential usefulness of thyroid hormones as a primary treatment to accelerate antidepressant response seems to have been lost in the literature.…”

31P-Magnetic Resonance Spectroscopy and Thyroid Hormones in Major Depressive Disorder: Toward a Bioenergetic Mechanism in Depression?

“…In severely treatment-resistant inpatient MDD subjects, there was no evidence of T3 augmentation of tricyclic antidepressants. 55 Out of five double-blind, controlled studies 56−60 on thyroid hormone augmentation of tricyclic antidepressants, three 57,59,60 reported positive results, with response rates ranging from 50 to 65%. The earlier studies in this group, 56−58 including the two negative studies, 56,58 had important methodological limitations.…”

Hormones in the Treatment of Depression

“…In addition, reduced thyroid activity may result in decreased β-adrenergic receptor Hormones in the treatment of depression -REVIEW activity, in which catecholamine transmission is functionally decreased [79]. Ever since antidepressant effects were reported for T3 in 1958 [80], several case studies and clinical trials have examined the treatment of depressive disorders with the use of adjunctive T3 [81][82][83][84][85][86][87][88][89][90][91][92][93][94][95]. Three case reports described the use of T3 augmentation of trazodone [81], phenelzine [82] and fluoxetine [83], in which the addition of T3 potentiated the effects of the respective antidepressants.…”

“…Three case reports described the use of T3 augmentation of trazodone [81], phenelzine [82] and fluoxetine [83], in which the addition of T3 potentiated the effects of the respective antidepressants. Open-label trials examined the use of adjunctive T3 (25-50 μg) in selective serotonin-reuptake inhibitor (SSRI)- [84][85][86] and tricyclic antidepressent (TCA)-resistant [87] MDD (Table 1). Two recent double-blind, placebo-controlled studies of adjunct T3 treatment for depression have shown the reverse with regard to the antidepressants [88,89].…”