David Baxter PhD
Late Founder
Thyroid Augmentation: Reassessing an Overlooked Strategy
by Norman Sussman, MD
Primary Psychiatry. 2007;14(7):14-15
The interview with Russell T. Joffe, MD, that appeared in the June 2007 issue of Primary Psychiatry1 focused my attention on the use of thyroid augmentation in psychiatry to enhance antidepressant drug response. It reminded me of when I was a resident and first heard Arthur Prange, Jr., MD, in 1975 describe the successful use of this strategy. I then wondered why I do not routinely use thyroid hormone as an intervention for my treatment-resistant patients. Study results are mixed. However, as Dr. Joffe pointed out, a meta-analysis of clinical trials showed that patients taking triiodothyronine (T3) are twice as likely to respond to antidepressant treatment versus placebo. He noted that there is consistency across these studies that augmentation with T3 is effective with tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs).
A small study published last year involved the addition of T3 to treat depression in patients with non-hypothyroid major depressive disorder (MDD) who failed to respond to an adequate course of standard SSRI treatments.2 All patients continued taking the same SSRI that they had been taking before they entered the study and were started on 25 μg of T3. The dose was increased to 50 μg within a week when tolerated. It was found that T3 augmentation resulted in improvement of mood scores, with a response rate of 42%. The authors concluded that, ?with the availability of T3?a viable, safe, inexpensive, and effective augmentation treatment?the recent trend of replacing T3 with other novel strategies appears unwarranted.?
Nierenberg and colleagues3 compared the effectiveness of lithium versus T3 augmentation as a third-step in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study protocol for treating patients with MDD. A total of 142 adult outpatients with nonpsychotic MDD who had not achieved remission or who were intolerant to an initial prospective treatment with citalopram and a second switch or augmentation trial were randomly assigned to augmentation with lithium (up to 900 mg/day; n=69) or with T3 (up to 50 μg/day; n=73) for up to 14 weeks. After approximately 10 weeks of treatment, remission rates were 15.9% with lithium augmentation and 24.7% with T3 augmentation. The difference between treatments was not statistically significant, but this may simply reflect the small sample size involved. The authors reported that lithium was more frequently associated with side effects, which led more participants from the lithium group to leave treatment. Echoing the comments made by the investigators in the study mentioned above,2 the STAR*D study team concluded that the lower side-effect burden and ease of using T3 augmentation suggest that it is slightly more advantageous than lithium augmentation for depressed patients who have experienced several failed medication trials.3
Despite the evidence that thyroid augmentation can improve and accelerate antidepressant response in euthyroid depressed patients, almost every endocrinologist I have talked to is either skeptical or hostile to the practice. The most common objection is that it does not make physiologic sense. Some are concerned about serious long-term complications. One such complication is osteoporosis. While some studies are reassuring on this issue,4 very little available data address long-term effects of T3 or thyroxine (T4) on bone mineral density in patients with mood disorders. Some evidence does suggest that thyroid hormone treatment for ≥1 year may adversely affect postmenopausal women with mood disorders.5
Some endocrinologists focus on cardiac risks. Long-term thyroid hormone augmentation may produce cardiac hypertrophy, lead to high output failure, and increase atrial irritability.6
The concerns of my colleagues have made me more cautious about using T3 or T4 with my patients. Based on my clinical experience, some patients do remarkably well when thyroid hormone is added to their antidepressants. Compared to some of the side effects associated with antidepressants, the tolerability profile of thyroid hormone is typically benign. Clearly, we need to conduct more studies of this intervention. Endocrinologists should take part in the design and analysis of these studies. The issue, it seems, is not whether thyroid augmentation works, but whether there are possible long-term complications that need to be recognized.
References
1 Joffe RT, Sussman N. In session with Russell T. Joffe, MD: the impact and psychological manifestations of thyroid dysfunction. Primary Psychiatry. 2007;14(6):36-38.
2 Abraham G, Milev R, Stuart Lawson J. T3 augmentation of SSRI resistant depression. J Affect Disord. 2006;91(2-3):211-215.
3 Nierenberg AA, Fava M, Trivedi MH, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry. 2006;163(9):1519-1530.
4 Gyulai L, Jaggi J, Bauer MS, et al. Bone mineral density and l-thyroxine treatment in rapidly cycling bipolar disorder. Biol Psychiatry. 1997;41(4):503-506.
5 Gyulai L, Bauer M, Garcia-Espana F, et al. Bone mineral density in pre- and post-menopausal women with affective disorder treated with long-term L-thyroxine augmentation. J Affect Disorder. 2001;66(2-3):185-191.
6 Bedotto JB, Gay RG, Graham SD, Morkin E, Goldman S. Cardiac hypertrophy induced by thyroid hormone is independent of loading conditions and beta adrenoceptor blockade. J Pharmacol Exp Ther. 1989;248(2):632-636.
by Norman Sussman, MD
Primary Psychiatry. 2007;14(7):14-15
The interview with Russell T. Joffe, MD, that appeared in the June 2007 issue of Primary Psychiatry1 focused my attention on the use of thyroid augmentation in psychiatry to enhance antidepressant drug response. It reminded me of when I was a resident and first heard Arthur Prange, Jr., MD, in 1975 describe the successful use of this strategy. I then wondered why I do not routinely use thyroid hormone as an intervention for my treatment-resistant patients. Study results are mixed. However, as Dr. Joffe pointed out, a meta-analysis of clinical trials showed that patients taking triiodothyronine (T3) are twice as likely to respond to antidepressant treatment versus placebo. He noted that there is consistency across these studies that augmentation with T3 is effective with tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs).
A small study published last year involved the addition of T3 to treat depression in patients with non-hypothyroid major depressive disorder (MDD) who failed to respond to an adequate course of standard SSRI treatments.2 All patients continued taking the same SSRI that they had been taking before they entered the study and were started on 25 μg of T3. The dose was increased to 50 μg within a week when tolerated. It was found that T3 augmentation resulted in improvement of mood scores, with a response rate of 42%. The authors concluded that, ?with the availability of T3?a viable, safe, inexpensive, and effective augmentation treatment?the recent trend of replacing T3 with other novel strategies appears unwarranted.?
Nierenberg and colleagues3 compared the effectiveness of lithium versus T3 augmentation as a third-step in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study protocol for treating patients with MDD. A total of 142 adult outpatients with nonpsychotic MDD who had not achieved remission or who were intolerant to an initial prospective treatment with citalopram and a second switch or augmentation trial were randomly assigned to augmentation with lithium (up to 900 mg/day; n=69) or with T3 (up to 50 μg/day; n=73) for up to 14 weeks. After approximately 10 weeks of treatment, remission rates were 15.9% with lithium augmentation and 24.7% with T3 augmentation. The difference between treatments was not statistically significant, but this may simply reflect the small sample size involved. The authors reported that lithium was more frequently associated with side effects, which led more participants from the lithium group to leave treatment. Echoing the comments made by the investigators in the study mentioned above,2 the STAR*D study team concluded that the lower side-effect burden and ease of using T3 augmentation suggest that it is slightly more advantageous than lithium augmentation for depressed patients who have experienced several failed medication trials.3
Despite the evidence that thyroid augmentation can improve and accelerate antidepressant response in euthyroid depressed patients, almost every endocrinologist I have talked to is either skeptical or hostile to the practice. The most common objection is that it does not make physiologic sense. Some are concerned about serious long-term complications. One such complication is osteoporosis. While some studies are reassuring on this issue,4 very little available data address long-term effects of T3 or thyroxine (T4) on bone mineral density in patients with mood disorders. Some evidence does suggest that thyroid hormone treatment for ≥1 year may adversely affect postmenopausal women with mood disorders.5
Some endocrinologists focus on cardiac risks. Long-term thyroid hormone augmentation may produce cardiac hypertrophy, lead to high output failure, and increase atrial irritability.6
The concerns of my colleagues have made me more cautious about using T3 or T4 with my patients. Based on my clinical experience, some patients do remarkably well when thyroid hormone is added to their antidepressants. Compared to some of the side effects associated with antidepressants, the tolerability profile of thyroid hormone is typically benign. Clearly, we need to conduct more studies of this intervention. Endocrinologists should take part in the design and analysis of these studies. The issue, it seems, is not whether thyroid augmentation works, but whether there are possible long-term complications that need to be recognized.
References
1 Joffe RT, Sussman N. In session with Russell T. Joffe, MD: the impact and psychological manifestations of thyroid dysfunction. Primary Psychiatry. 2007;14(6):36-38.
2 Abraham G, Milev R, Stuart Lawson J. T3 augmentation of SSRI resistant depression. J Affect Disord. 2006;91(2-3):211-215.
3 Nierenberg AA, Fava M, Trivedi MH, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry. 2006;163(9):1519-1530.
4 Gyulai L, Jaggi J, Bauer MS, et al. Bone mineral density and l-thyroxine treatment in rapidly cycling bipolar disorder. Biol Psychiatry. 1997;41(4):503-506.
5 Gyulai L, Bauer M, Garcia-Espana F, et al. Bone mineral density in pre- and post-menopausal women with affective disorder treated with long-term L-thyroxine augmentation. J Affect Disorder. 2001;66(2-3):185-191.
6 Bedotto JB, Gay RG, Graham SD, Morkin E, Goldman S. Cardiac hypertrophy induced by thyroid hormone is independent of loading conditions and beta adrenoceptor blockade. J Pharmacol Exp Ther. 1989;248(2):632-636.
