Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors

Abstract

The thyroid hormone, triiodothyronine (T3), is used as a supplement to antidepressant treatment of major depression, to accelerate and enhance response and as an augmenter in patients who have not responded. While there is support from controlled trials and meta-analyses for the use of T3 in conjunction with tricyclic antidepressants, the evidence base for supplementation of specific serotonin reuptake inhibitors (SSRIs) with T3 is more limited. We reviewed the available literature on T3 supplementation of SSRIs including open-label studies and randomized controlled trials (RCTs). Five RCTs were identified. Three were enhancement studies in which T3 was administered concurrently with the antidepressant from the start of treatment and two were augmentation studies in which T3 was added to the antidepressant treatment of patients who had not responded. Three open augmentation studies were identified. The RCTs were too disparate in methodology to allow a meta-analysis to be performed. The enhancement studies are inconclusive in that one showed strongly positive effects of T3, one showed no effect and one showed a trend. The open augmentation studies supported an effect of T3 in SSRI non-responsive patients with some support from a large RCT; a smaller, underpowered RCT did not show efficacy. T3 was well tolerated in most of the studies and adverse effects do not seem to be an impediment to clinical use. Some of the studies identified clinical and thyroid function correlates of response that require further investigation. Further research is needed before it can be definitively established whether T3 is an effective supplement to SSRIs in patients with MDD. The appropriate timing of T3 supplementation needs to be explored and also the dose and length of treatment.

The Integrative Management of Treatment-Resistant Depression: A Comprehensive Review and Perspectives

“…There are several open-label trials supporting the efficacy of T 3 augmentation of SSRI for TRD, as reviewed by Cooper-Kazaz and Lerer [64]. However, a single RCT did not show differences between T 3 , lithium and T 3 plus lithium as augmenting agents for TRD [65].…”

Utilizing the <em>DSM-5</em> Anxious Distress Specifier to Develop Treatment Strategies for Patients With Major Depressive Disorder

“…Thyroid hormone supplementation may be useful in some patients with treatment-resistant depression; evidence in the literature is mixed. 67 Lithium is another augmentation option, with a meta-analysis 68 confirming its effectiveness. A third option is l-methylfolate, which is well tolerated and also may be useful in some patients.…”

Evidence for the Benefits of Nonantipsychotic Pharmacological Augmentation in the Treatment of Depression

“…Previous studies have focused on the augmentation of T3 in TCA-refractory depression; therefore, Cooper-Kazaz and colleagues [34] conducted a meta-analysis on five RCTs; three were enhancement studies in which T3 was administered concurrently with the SSRIs from the start of treatment, and two were augmentation studies in which T3 was added for patients who had not responded to SSRI treatment. They found that the two open augmentation studies were too disparate in methodology to allow metaanalysis.…”