Hypothyroidism, T3, Mental Function, and Depression: Medical Journals

Purpose of this compilation

To show that treating hypothyroidism with T3 (triiodothyronine) in addition to T4 (thyroxine) can markedly improve mental function and reduce depression in hypothyroid patients.

See also the links in the right column as well as in our Desiccated Thyroid References and TSH References sections.

A. T3 and mental function
B. T3 and depression

A. T3 and mental function

1. "Thyroxine vs thyroxine plus triiodothyronine in treatment of hypothyroidism after thyroidectomy for Graves' disease" (Lithuania, 2002)

The substitution of 10 microg of T3 for 50 microg of T4 caused a statistically significant decrease in free T4 concentration but no significant change in T3 or thyroid-stimulating hormone concentration. Symptoms of hypothyroidism and of hyperthyroidism tended to decrease on a standard symptom scale after combined treatment. With combined hormone replacement, mental state tended to improve on some mood scales but not on cognitive tests....These preliminary findings in a small group of patients with Graves' disease are consistent with earlier findings that thyroid replacement with T4-T3 combination improves mental functioning.

2. "Mental improvement after replacement therapy with thyroxine plus triiodothyronine: relationship to cause of hypothyroidism" (US, 2000)

After combined hormone treatment there were clear improvements in both cognition and mood, the latter changes being greater.

3. "Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism" (Lithuania and US, 1999)

In patients with hypothyroidism, partial substitution of triiodothyronine [T3] for thyroxine [T4] may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.

B. T3 and depression

1. "Algorithm-based treatment of major depression in an outpatient clinic: clinical correlates of response to a specific serotonin reuptake inhibitor and to triiodothyronine augmentation" (Israel, 2003)

Addition of T3 was effective [for treating depression] in 10 out of 16 women (62.5%) while none of the 9 males responded. Although values were within the normal range, patients who responded to T3 had higher serum thyroid-stimulating hormone levels than those who did not....The effect of T3 may be related to thyroid function even within the normal range.

2. "Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature." (US, 2001)

Six studies were identified. All were conducted with triiodothyronine (T(3)) and a tricyclic antidepressant. Five of the six studies found T(3) to be significantly more effective than placebo in accelerating clinical response....the effects of T(3) acceleration were greater as the percentage of women participating in the study increased.

3. "Hypothyroidism and Depression: A Therapeutic Challenge" (US, 2000)

Depressed patients should be screened for hypothyroidism. In hypothyroid patients, depression may be more responsive to a replacement regimen that includes T3 rather than T4 alone. Therefore, inclusion of T3 in the treatment regimen may be warranted after adequate trial with T4 alone.

4. "[Thyroid function in depressed patients]" [Article in French; abstract in English] (Switzerland, 1996)

...we concluded that FT3 and TSH levels were significantly lower in the depressed group...and that FT4 was slightly but not significantly increased in the depressed group. FT3 decrease and the slight FT4 increase in depression may be the consequence of a metabolic deviation of FT4 transformation into FT3. Its link with intensity and polarity of depression suggests that it can be considered as a biological marker of this disease.

5. "T3 augmentation of antidepressant treatment in T4-replaced thyroid patients" (Canada, 1992)

We now report on the successful use of T3 augmentation therapy in seven of nine depressed patients who were also receiving T4 for thyroid disease....Seven of the nine patients were judged to respond to T3 augmentation. CONCLUSION: These results are consistent with a report of differential effects for T3 versus T4 augmentation in depressed patients free of thyroid disease. The results have implications for the treatment of depression in the presence of thyroid disease and for the mechanism of thyroid hormone potentiation of antidepressants.