Background: Many studies of thyroid augmentation in refractory depression are methodologically weak, have had mixed results, and often do not include biological measures of hormonal effects. In this paper, recent clinical and preclinical research on thyroid dysfunction in refractory depression is reviewed.
Method: A search of MEDLINE for articles published from 1970 to the present was conducted, in addition to a search of the bibliographies of published papers in this area. The clinical studies chosen for review included those in which the patient population was identified as having refractory depression and where a specific measure of thyroid function was used, such as thyroid indices, thyroid-releasing hormone stimulation, or basal metabolic rate. Animal studies of depression using the learned helplessness experimental paradigm were also reviewed and included if they examined the factors involved in antidepressant treatment response.
Results: Fifty-two percent of patients with refractory depression in six clinical studies evidenced subclinical hypothyroidism (range, 29%-100%), which can be contrasted with a prevalence of approximately 8% to 17% in unselected populations of depressed patients. Four studies investigating an animal model of refractory depression strongly implicate a pathophysiologic role for hypothyroidism, perhaps mediated by altered beta-adrenergic function.
Conclusion: These findings indicate that hypothyroidism is significantly associated with refractory depression, suggesting that this characterizes one biological subtype of refractory depression. Failure to rigorously investigate the effects of thyroid augmentation, including measures of thyroid and beta-adrenergic function, may partly explain the ambiguous results from many treatment studies, and future research should incorporate these measures in the study of refractory depression.