Effects of selective serotonin reuptake inhibitors on thyroid function in depressed patients with primary hypothyroidism or normal thyroid function

Abstract

BACKGROUND: Several studies with ambiguous results have examined the effects of selective serotonin reuptake inhibitors (SSRIs) on thyroid function. This study aimed to establish the effects of fluoxetine and sertraline treatments on thyroid function and thyroid autoimmunity in patients with major depression and primary hypothyroidism and in patients with major depression and normal thyroid function. METHODS: This was a prospective, controlled, intervention study involving 67 subjects: 28 patients with major depression and hypothyroidism on adequate levothyroxine therapy randomized for treatment with fluoxetine (n = 13) or sertraline (n = 15); 29 patients with major depression and normal thyroid function treated with fluoxetine (n = 15) or sertraline (n = 14) and 10 control patients with hypothyroidism on adequate levothyroxine therapy without depression. Main outcome measures included thyrotropin, thyroxine (T(4)), free thyroxine, triiodothyronine (T(3)), anti-thyroid peroxidase antibodies, and Hamilton depression (HAM-D) rating scale. RESULTS: Patients with normal thyroid function who were treated with fluoxetine demonstrated a significant reduction of T(3) after 15 and 30 days of treatment (p = 0.034 and p = 0.011) and a significant reduction of T(4) throughout the intervention period (p = 0.04 after 15 days; p = 0.015 after 30 days; and p = 0.029 after 90 days). However, all thyroid parameters remained within the euthyroid range. No changes were observed among hypothyroid patients on levothyroxine replacement therapy who were treated with either SSRI. The degree of improvement in depression symptoms (HAM-D rating scale) after 90 days of SSRI treatment was correlated with T(3) levels reduction among patients with normal thyroid function randomized for sertraline and among patients with hypothyroidism randomized for fluoxetine. T(3) levels remained within the euthyroid range during the study period. CONCLUSIONS: Neither fluoxetine nor sertraline was associated with clinically significant changes in thyroid function or thyroid autoimmunity in either primary hypothyroid or normal thyroid function patients with depression. However, results suggest that patients with normal thyroid function who were treated with fluoxetine are more susceptible to minor changes within the serotoninergic system than patients with hypothyroidism on the same SSRI therapy. To the best of our knowledge, this is the first study to demonstrate the safety of administering SSRIs in hypothyroid patients.