Worse Outcomes in Patients With Depression Linked to Low Thyroid Hormones

Lower levels of certain thyroid hormones may predict a poor treatment response in people with depression, even when these hormones fall within the normal range, a study in the Journal of Affective Disorders suggests.

Lead author Zhifen Liu, M.D., an associate professor in the Department of Psychiatry at First Hospital of Shanxi Medical University, in Taiyuan, China, told Psychiatric News that the findings build upon both existing research and the researchers’ own clinical observations of patients with depression.

“From the clinical point of view, we noticed that depressive symptoms were frequently associated with clinical hypothyroidism and subclinical hypothyroidism. Such hypothyroidism also seems to affect the clinical outcome of patients with depression,” Liu said. “However, most patients with depression do not have biochemical evidence of thyroid dysfunction, with their hormones still not extending [outside the normal] range.”

Liu and colleagues studied data from 2,086 patients who were admitted to the hospital with depression between 2014 and 2020. All patients had thyroid function evaluations—including measures of serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH)—the morning after they were admitted. The patients’ depression symptoms were measured using the Hamilton Depression Scale (HAM-D). The researchers analyzed changes in the patients’ HAM-D scores from the time the patients were admitted until they were discharged.

After controlling for the patients’ age, education level, and other factors, the researchers found that lower levels of FT4 on admission were significantly associated with higher HAM-D scores; lower levels of FT3 on admission were significantly associated with longer stays in the hospital—even when the levels of these hormones were within the normal range. The researchers also found that higher FT4 levels on admission were associated with greater improvements in HAM-D scores over the course of treatment between admission and discharge.

Liu said that the findings underscore the need for thyroid and depression screening.

“When treating patients with depression, we think patients with lower levels of thyroid hormone may be most in need of earlier and more intensive interventions to prevent continued dysfunction,” Liu said. “We advise psychiatrists to run thyroid tests for all of their patients with depression. Considering the relationship between thyroid disorders and depression, and the higher comorbidity rate in these two diseases, we also advise physicians to screen patients with thyroid disorders for depression.”

Liu said that supplementing thyroid hormones may augment and accelerate treatment with antidepressants and added that thyroid hormones are part of an overall picture that mental health professionals should consider with respect to depression.

“In my opinion, in clinical diagnosis and treatment, psychiatrists and other mental health professionals should not only pay attention to the symptoms of patients with depression, but also pay more attention to [the patients’] physiological indicators, including but not limited to metabolic indicators such as thyroid hormone and uric acid, vital signs such as heart rate and blood pressure, and even imaging markers such as brain function and structure.”

Bruce Cohen, M.D., Ph.D., Robertson-Steele Professor of Psychiatry at Harvard Medical School and director of the Program for Neuropsychiatric Research at McLean Hospital in Belmont, Mass., said the results of this study confirm those of prior research, including his own.

“Past research and reviews consistently observe that individuals without outright thyroid disease, but with evidence of lower-than-average thyroid function, tend to be poorer responders to antidepressant treatment,” Cohen told Psychiatric News. “Of immediate note is the additional evidence that patients with thyroid function tests in the ‘normal’ range, as defined by standard lab reports, may experience inadequate treatment response related to thyroid inadequacy.”

In a study in the July 2018 American Journal of Psychiatry, Cohen and his team had previously reported that TSH levels at the high end of normal, which tend to be associated with low thyroid hormone levels, indicated a greater risk of poor response to antidepressants. “In the current paper, they note that low levels of the thyroid hormones T3 and T4, themselves, may be associated with poor response,” Cohen explained. “Clinicians should be aware of the value of obtaining thyroid tests in patients with poor response to antidepressants or other treatments. [However], exactly what steps to take in patients with thyroid measures suggesting inadequate hormone levels remains a matter of discussion and investigation.”

Liu’s study was supported by the National Natural Science Foundation of China, the Key Research and Development Project (International Cooperation) of Shanxi Province, Shanxi Province Science Foundation for Youths, Shanxi Scholarship Council of China, and The First Hospital of Shanxi Medical University Foundation for Youths Innovation. ■

“Exploring the Potential of Thyroid Hormones to Predict Clinical Improvements in Depressive Patients: A Machine Learning Analysis of the Real-World Based Study” is posted here.

“Antidepressant-Resistant Depression in Patients With Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels” is posted here.