An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms

Abstract

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck’s Depression Inventory (BDI) scale (range 0–63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval = − 0.17 to 0.76, I2 = 15.6) or subclinical hyperthyroidism (− 0.10, 95% confidence interval = − 0.67 to 0.48, I2 = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.

Thyroid Function and Mood Disorders: A Mendelian Randomization Study

“…As our genetic variants do not only associate with normal-range thyroid function, but a genetic risk score based on our TSH-associated variants also strongly associates with both subclinical hypo- and hyperthyroidism ( 35 ), the results of the current study suggest that there is neither any noteworthy causal effect of subclinical thyroid dysfunction on MDD risk. While in contrast to some previous observational studies ( 8 ), this is in line with the results of a recent large-scale (N=23,038) analysis of individual-level data from several prospective cohorts ( 65 ).…”

Effect of Levothyroxine Therapy on the Development of Depressive Symptoms in Older Adults With Subclinical Hypothyroidism

“… 32 , 33 , 34 , 35 , 36 , 37 , 38 However, our recently conducted individual participant data (IPD) analysis, including younger and older participants, revealed no prospective association between subclinical hypothyroidism and depressive symptoms. 39 Previous clinical trials were rather small and could not find an effect of levothyroxine therapy on depressive symptoms. 29 , 30 , 31 , 40 …”

Interaction Mechanisms Between Major Depressive Disorder and Non-alcoholic Fatty Liver Disease

“…About 4-40% of patients with affective disorders have SCH (171,172), and the prevalence of SCH in female MDD patients is about twice that of males (173). However, some studies have reported contrasting conclusions to the effect that there is no correlation between SCH and depression (174,175). Other studies have documented that the prevalence and incidence of hypothyroidism or hyperthyroidism in patients with severe MDD are higher than those of the general population (176).…”