What is the role of Triiodothyronine (T3) augmentation in the treatment of depression?

From the Guidelines

T3 augmentation is a viable treatment strategy for patients with treatment-resistant depression, as evidenced by its successful use in augmenting standard antidepressant treatments 1. The role of Triiodothyronine (T3) augmentation in the treatment of depression is supported by research indicating that some patients with depressive disorders exhibit subclinical forms of hypothyroidism, and T3 has been used to augment standard first-line treatments, such as antidepressants 1. Key considerations for T3 augmentation include:

• Starting with a dose of 25 mcg daily, which can be increased to 50 mcg if needed after 2-4 weeks
• Taking the medication in the morning to avoid sleep disturbances
• Monitoring thyroid function and heart rate regularly
• Being aware of potential side effects, including palpitations, anxiety, insomnia, and weight loss
• Contraintications, such as hyperthyroidism, recent heart attack, or uncorrected adrenal insufficiency T3 augmentation works by enhancing neurotransmitter activity and improving brain metabolism, complementing the effects of traditional antidepressants, and most patients see improvement within 2-4 weeks 1. It is essential to note that T3 augmentation should be managed by a psychiatrist or physician experienced with this approach, and treatment typically continues for at least 6-12 months if effective. Before starting T3 augmentation, thyroid function tests should be performed to ensure the patient does not have hyperthyroidism or other contraindications 1.

From the FDA Drug Label

Thyroid hormones enhance oxygen consumption by most tissues of the body and increase the basal metabolic rate and the metabolism of carbohydrates, lipids and proteins. The clinical features of myxedema coma include depression of the cardiovascular, respiratory, gastrointestinal and central nervous systems, impaired diuresis, and hypothermia. Administration of thyroid hormones reverses or attenuates these conditions Thyroid hormones increase heart rate, ventricular contractility and cardiac output, as well as decrease total systemic vascular resistance. They also increase the rate and depth of respiration, motility of the gastrointestinal tract, rapidity of cerebration, and vasodilatation

The role of Triiodothyronine (T3) augmentation in the treatment of depression is not directly addressed in the provided drug label. The FDA drug label does not answer the question.

From the Research

Role of Triiodothyronine (T3) Augmentation in Depression Treatment

• T3 augmentation has been used in treatment-resistant depression, with studies showing varying degrees of success 2, 3, 4, 5.
• A study published in 2007 found that adding l-thyroxine (T4) to serotonergic antidepressants resulted in remission in 64.7% of female patients with treatment-resistant depression 2.
• However, a 2004 study found that T3 addition to paroxetine did not accelerate clinical response or improve treatment outcomes in non-refractory major depressive disorder 3.
• Another study published in 2003 found that T3 augmentation was effective in 62.5% of female patients who did not respond to SSRI treatment, but none of the male patients responded 4.
• A review of the literature on T3 supplementation of SSRIs found that the evidence base is limited, but suggests that T3 may be an effective supplement to SSRIs in patients with major depressive disorder 5.
• T3 augmentation is also mentioned as a strategy for treatment-resistant depression, with lithium and T3 augmentation of tricyclic agents being the best-studied strategy 6.

Efficacy and Safety of T3 Supplementation

• The efficacy and safety of T3 supplementation in patients with major depressive disorder treated with SSRIs has been reviewed, with findings suggesting that T3 is well-tolerated and may be an effective supplement to SSRIs 5.
• However, the evidence base is limited, and further research is needed to establish the effectiveness of T3 supplementation in this population 5.
• T3 augmentation has been found to be effective in some studies, but not others, highlighting the need for further research to determine the optimal timing, dose, and duration of T3 treatment 3, 4, 5.

Clinical Correlates of Response to T3 Augmentation

• Some studies have identified clinical and thyroid function correlates of response to T3 augmentation, including higher serum thyroid-stimulating hormone levels in patients who responded to T3 4.
• Further research is needed to investigate these correlates and determine the optimal patient population for T3 augmentation 5.