T3 Supplementation for Treatment-Resistant Depression

Condition: DepressionResources: Depression Treatment
Written By Dr. David Danish

Dr. Danish frequently works with patients using various treatments to manage depression, including T3 supplementation. T3, or triiodothyronine, is a thyroid hormone that plays a crucial role in regulating metabolism, energy production, and mood. For patients with treatment-resistant depression, adding T3 supplementation can offer considerable efficacy when other medications have not. 

T3 supplementation has shown promise in enhancing the effects of antidepressants and improving mood in patients with both unipolar and bipolar depression. This treatment is based on the understanding that individuals with depression often have lower production of adenosine triphosphate (ATP), which is necessary for transporting thyroid hormone into cells where it can exert its actions. Even if thyroid hormone levels are normal in the blood, those with depression might still experience symptoms of hypothyroidism. By addressing this imbalance, T3, or Cytomel, which is shorter-acting and reaches a steady state more quickly than other thyroid medications, can help alleviate depressive symptoms and improve overall well-being, particularly in patients with treatment-resistant depression.

Theories and Evidence

Research suggests that those with depression tend to have lower production of ATP, which is required to transport thyroid hormone into the cells. This means that even with normal blood levels of thyroid hormone, patients may experience hypothyroidism-like symptoms. Additionally, evidence indicates that T3 supplementation does not trigger mania in patients with bipolar depression and can actually improve mixed states.

In augmentation studies, two RCTs and three open-label studies examined adding T3 to ongoing SSRI treatment in patients who had not responded to SSRIs alone. Agid and Lerer (2003) reported a 40% response rate and a 36% remission rate. Iosifescu et al. (2005) found a 35% response rate and a 30% remission rate. Abraham et al. (2006) reported a 41.7% response rate and a 25% remission rate. Nierenberg et al. (2006) in the STAR*D study found a 24.7% remission rate with T3 augmentation, compared to 15.9% with lithium augmentation.

Side Effects and Considerations

Starting T3 supplementation may cause:

  • Feeling hot

  • Increased anxiety

  • Higher heart rate (it is recommended to lower caffeine intake)

If there is tachycardia (HR > 100 at rest), the dose may need to be lowered. Long-term side effects of hyperthyroidism, such as osteoporosis and heart arrhythmias, have not been observed in studies focused on depression treatment. For a comprehensive list of side effects, please visit webmd.com. 

Dosing and Duration

The typical dosing schedule for T3 is:

  • Start at 25 mcg/day for 7 days

  • Increase to 50 mcg/day for 7 days, then get vitals

  • Increase to 75 mcg/day for 7 days, then 100 mcg/day for 7 days before follow-up

The goal dose ranges from 50-150 mcg/day, and treatment typically continues for at least six months, with many patients remaining on T3 for several years.

Pre-Treatment Lab Tests

Before starting T3 supplementation, it is important to conduct thyroid studies to rule out existing hypothyroidism or hyperthyroidism. If these conditions are present, a consultation with an endocrinologist is recommended.

Additional Benefits

Interestingly, T3 supplementation can also help with anxiety, despite seeming counterintuitive. This makes it a valuable addition to the treatment plans for patients struggling with both depression and anxiety.

For More on This Topic and Related Subjects, Check Out These Blogs:

  • Ketamine for Depression provides an overview of the use of ketamine in treating depression, including its efficacy and potential side effects.

  • Discover just how powerful TMS is for depression.

  • In some patients, inflammation may be playing at least a partial role in their depressive symptoms. 

  • Learn about the off-label use of pramipexole in treating unipolar and bipolar depression. 

  • TCAs, or Tricyclic Antidepressants are an older class of antidepressants with more side effects than newer options; however, for some patients they are a lifesaver. 

  • Monoamine oxidase inhibitors (MAOIs) are one of the oldest, yet most effective classes of antidepressants. But they come with strict warnings about certain foods and medications. 

Disclaimer

Dr. Danish creates these handouts based on research, but they are not meant to be 100% comprehensive. Patients are invited to discuss the ideas brought up in this document with their provider. For full lists of side effects on medications and supplements, visit drugs.com and webmd.com, as these lists are always expanding with more research.

Sources



Dr. David Danish
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