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Next, let’s look at thyroid augmentation in the treatment of major depression.
If you’re augmenting with thyroid hormone, what is your target TSH? Or, if it’s someone else’s thyroid treatment and you’re treating the patient with depression, what TSH should you encourage your colleagues to get the patient to? In a 2018 article by Harvard’s Bruce Cohen and colleagues in the American Journal of Psychiatry, they assert that a TSH of 2.5—even though that’s well within the normal range—is not normal. The title of the article is, “Antidepressant-Resistant Depression in Patients with Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels.” In other words, we’re looking at people with antidepressant-resistant depression, where you might think about thyroid augmentation, particularly if their TSH was kind of on the high end of normal. This paper asserts that a full trial of thyroid supplementation should get your target TSH down near 1, not just into the normal range, like 4. So, basically, what we’re looking at here is that high-normal TSH levels are not normal because they’re based on TSH scores from the general population.
Now, remember, a laboratory normal range is defined by taking a bell-shaped curve of the distribution of a value in a population and then cutting off 2.5% at each end by convention such that we have 95% of the population within the bell-shaped curve. But the problem here is that TSH is not bell shaped. Its distribution in the population is not bell shaped. There is a big skew such that the majority of the population is down around 1.5. There’s a long tail that begins around 2. And by 2.5, you’re well out into the tail of this skewed curve such that 90% to 95% of the population lives below 2.5.
According to Cohen and colleagues in this article, the upper limit of normal of TSH (at least for our purposes, in terms of treating mood disorders) is more like 2.5. It strengthens the justification for using thyroid as your augmentation agent when TSH is up there around 3.5 or 4 even though it’s in the normal range. So, this paper is sort of a review of the use of thyroid hormone in depression, and they emphasized a large study in which the depression rate was twice as high in women with TSH levels above 2.3. In other words, they think the optimum level of TSH in patients with mood disorders is well below the upper limit of normal.
What about the risks of adding thyroid hormone and pushing TSH down below 2.5? Cohen and colleagues note that the most common worrisome side effect of thyroid hormone treatment is atrial fibrillation. But according to them, that’s “rare and usually seen only if TSH is driven very low, below 0.1.” Well, one of our colleagues, Dr. Tam Kelly, argues that atrial fibrillation is not clearly associated with exogenous thyroid at all, and that the association comes from patients with afib who have endogenous high levels of thyroid. In other words, they’re hyperthyroid. So, hyperthyroidism and afib are clearly associated. But for exogenous thyroid, Dr. Kelly urges us to look at the endocrinology research on high-dose thyroid for the suppression of thyroid cancer. He’s published literature reviews from 2015 both on afib and decreased bone density that suggest that exogenous thyroid may not carry those kinds of risks. For more on that, see Tam Kelly’s “The Art and Science of Thyroid Supplementation.” That’s a monograph of his summarizing his literature reviews.
Back to Cohen et al., who are not quite as aggressive as Dr. Kelly, but they’re publishing in the American Journal of Psychiatry. They assert that TSH level should be driven below 2 unless side effects, such as agitation, intervene. They even go so far as to say that, in their own practice, unless response is seen at a lower dose, “we often attempt to achieve enough thyroid hormone supplementation to drive the TSH to 1.0 or just below.” In other words, in their view, if you’re going to use it, get below 2, and target something maybe closer to 1.
In summary, we are possibly not being aggressive enough when we use thyroid hormone targeting mood. And if the patient is already on thyroid from one of our colleagues and the patient has depression, we should be talking to our colleagues about trying to drive that TSH down somewhere between 1 and 2. Dr. Kelly would assert that we ourselves ought to take over that prescribing. And if you lack confidence in that area, you now have an additional reason to read his monograph, “The Art and Science of Thyroid Supplementation.”
Abstract
Antidepressant-Resistant Depression in Patients With Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels
Bruce M. Cohen, M.D., Ph.D., Barbara R. Sommer, M.D., Alexander Vuckovic, M.D.
No abstract available
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Reference
Cohen, B. M., Sommer, B. R., & Vuckovic, A. (2018). Antidepressant-resistant depression in patients with comorbid subclinical hypothyroidism or high-normal TSH levels. American Journal of Psychiatry, 175(7), 598-604.
