‘Reconsider the paradigm’ of hypothyroidism, depression link, study suggests

The effect size for the correlation between hypothyroidism and clinical depression appeared significantly lower than previously thought, according to results of a systematic review and meta-analysis published in JAMA Psychiatry.

The correlation may exist solely among those with overt hypothyroidism and female individuals.

“A 2018 meta-analysis reported a substantial association of subclinical and clinical depression with hypothyroid autoimmunity,” Henry Bode, of the department of psychiatry and psychotherapy at the University of Cologne in Germany, and colleagues wrote. “With an odds ratio (OR) of 3.31, Siegmann [and colleagues] estimated that each year, more than 20% of patients with autoimmune thyroiditis experience depression. This meta-analysis has been criticized, for example, for its combination of population-based studies with results from outpatient clinics, with their bias toward more severely affected patients.”

Another meta-analysis showed a weak, nonsignificant link between hypothyroidism and depression (OR = 1.24); however, this individual patient data meta-analysis used only six studies and was restricted to subclinical hypothyroidism. Thus, it is unclear whether and how significantly hypothyroidism is associated with clinical depression, Bode and colleagues noted.

In the current study, they aimed to address this research gap by searching three databases from inception until May 2020 for epidemiologic and population-based studies that evaluated this potential association using ICD diagnoses of hypothyroidism and diagnoses of depression based on operationalized criteria or cutoffs in established rating scales. The association of clinical depression with either hypothyroidism or autoimmunity served as the prespecified coprimary outcomes.

The researchers included 25 studies, with a total of 348,014 participants, in the meta-analysis. They found an association between hypothyroidism and clinical depression (OR = 1.3; 95% CI, 1.08-1.57); however, the OR for autoimmunity was inconclusive (OR = 1.24; 95% CI, 0.89-1.74). According to subgroup analyses, a stronger association existed for overt than for subclinical hypothyroidism, with respective ORs of 1.77 (95% CI, 1.13-2.77) and 1.13 (95% CI, 1.01-1.28). Sensitivity analyses showed more conservative estimates. A post hoc analysis confirmed the association among female individuals (OR = 1.48; 95% CI, 1.18-1.85) but not among male individuals (OR = 0.71; 95% CI, 0.4-1.25).

“It may be time to reconsider the paradigm of a strong connection between hypothyroidism and depression,” Bode and colleagues wrote. “The results of other groups and our own findings indicate the contribution of hypothyroidism to the pandemic of depression is probably small. This is good news for patients with hypothyroidism or, in particular, with thyroid autoimmunity.”