Association between Hypothyroidism, Depression, and Anxiety Disorder – Results of Meta-Analyses
The prevalence of autoimmune thyroiditis in the USA ranges between 4 and 13%. Subclinical hypothyroidism affects 3–8.5% of the general population. Patients with this condition are at risk not only from somatic manifestations. The meta-analyses presented below examined the association between hypothyroidism and the incidence of psychiatric disorders – depressive and anxiety disorders. One of the meta-analyses also evaluated the effect of levothyroxine administration on the incidence of depression in individuals with subclinical hypothyroidism.
First Meta-Analysis
The first meta-analysis1 included 19 clinical studies involving 36,174 participants, based on a systematic search of the databases Google Scholar, EBSCO Host, Web of Knowledge, and PubMed conducted as of December 5, 2017. Depression incidence was evaluated in 35,168 patients and anxiety incidence in 34,094 patients.
Patients with autoimmune thyroiditis, Hashimoto's thyroiditis, or subclinical or clinically manifest hypothyroidism scored significantly higher on standardized depression assessment tools (odds ratio [OR] 3.56; 95% confidence interval [CI] 2.14–5.94; I2 = 92.1) and anxiety (OR 2.32; 95% CI 1.40–3.85; I2 = 89.8 %) compared to individuals with a euthyroid thyroid gland. Patients with autoimmune thyroiditis had a greater chance of developing symptoms of depression and anxiety and being diagnosed with depressive or anxiety disorders.
Second Meta-Analysis
The second meta-analysis2 included studies from the PubMed, CINAHL, and OVID databases published up to June 2017. The analysis assessed the prevalence of depressive disorder in patients with subclinical hypothyroidism (elevated TSH with normal fT4 and fT3 levels), serum TSH levels in patients with depressive disorder, and the effect of levothyroxine substitution on depression scores in patients with subclinical hypothyroidism and coexisting depression.
The first analysis included 15 studies with 12,315 participants, of whom 1700 (13.8%) had subclinical hypothyroidism. The average TSH level was 16.2 vs. 2.09 mIU/l in the control group (p < 0.001). Patients with subclinical hypothyroidism had a higher risk of depressive disorder than euthyroid controls (relative risk [RR] 2.36; 95% CI 1.84–3.02; p < 0.001). In the geriatric cohort of patients with subclinical hypothyroidism (aged over 60), the risk of depressive disorder was 1.7 times higher compared to the control group (OR 1.72; 95% CI 1.10–2.70; p = 0.020).
The second analysis included 7 studies with a total of 7135 participants (80.3% males), of whom 753 patients (57.0% males) had a depressive disorder. No significant difference was found in average TSH levels between these patients and the control group (2.30 ± 1.18 vs. 2.13 ± 0.72 mIU/l; p = 0.513).
The third analysis included 6 studies with 266 participants. The duration of levothyroxine therapy ranged from 2 to 12 months (mean 5.95 ± 4.09 months). In individuals with subclinical hypothyroidism and coexisting depression, levothyroxine substitution was not associated with improvement on the Beck Depression Inventory (d+ = −1.05; 95% CI −2.72 to 0.61; p = 0.215) or the Hamilton Depression Rating Scale (d = 2.38; 95% CI −4.86 to 0.10; p = 0.060).
Conclusion
According to the aforementioned meta-analyses, (subclinical) hypothyroidism is associated with depressive and anxiety disorders. Early diagnosis and initiation of adequate antidepressant/anxiolytic treatment are key to reducing morbidity and other related risks. Screening for depression and anxiety should thus be considered in patients with hypothyroidism and vice versa.
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Sources:
1. Siegmann E. M., Müller H. H. O., Luecke C. et al. Association of depression and anxiety disorders with autoimmune thyroiditis. JAMA Psychiatry 2018; 75 (6): 577–584, doi: 10.1001/jamapsychiatry.2018.0190.
2. Loh H. H., Lim L. L., Yee A. Association between subclinical hypothyroidism and depression: an updated systematic review and meta-analysis. BMC Psychiatry 2019; 19 (1): 12, doi: 10.1186/s12888-018-2006-2.
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