Effects of Selective Serotonin Reuptake Inhibitors on Thyroid Function in Depressed Patients with Primary Hypothyroidism or Normal Thyroid Function

SEMPR, Serviço de Endocrinologia e Metabologia, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
Thyroid: official journal of the American Thyroid Association (Impact Factor: 4.49). 08/2009; 19(7):691-7. DOI: 10.1089/thy.2008.0261
Source: PubMed


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.
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.
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.
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.

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    • "In addition, many studies performed in patients reveled controversial results and most of them have used tricyclic antidepressant instead selective serotonin reuptake inhibitors, SSRIs (de Carvalho et al., 2009). As considered by de Carvalho et al. (2009), it's important to know about the possible effects of SSRIs on thyroid function given its widespread utilization. Thus, to better define the complex relationship between thyroid hormones and stress-induced psychiatric disturbances, the present study evaluated the effects of short and long-term psychosocial stress on serum TH as well as on type 1 and type 2-deiodinase activity in many tissues of rats. "
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    ABSTRACT: Although serotonergic system has been classically implicated in mood modulation, there has been relatively little study on the relationship between this system and thyroid hormones (TH) economy in stress models. When TH are studied, the effects of stress on thyroid function seems to be complex and depend on the kind and time of stress which counts for the elusiveness of mechanisms underlying changes in TH economy. Herein, we hypothesized that serum TH are affected in a time-dependent fashion after repeated social stressful stimuli and serotonergic system is implicated in these changes. Therefore, we aimed to investigate the possible alterations in thyroid hormone economy and type 1 (D1) and type 2 (D2) deiodinase activity in a model of social defeat stress. Thereafter, we tested the responsiveness of these changes to fluoxetine treatment. Both short (STS) and a long-term (LTS) stress were performed. Blood samples were drawn just before and 1 (STS) or 4 and 8 weeks (LTS) after the beginning of stress to assess serum T4, T3 and corticosterone. Deiodinases activity was assessed at the end of each protocol. Stress-induced behavior studied in open field arena and hypercorticosteronemia were mainly observed in LTS (week 4). Stress-induced behavior was associated to hypothyroidism which occurred before, since week 1 in stressed group. Serum TH was restored to control levels in week 8, when behavior changes were not observed anymore, and was mainly associated with high brown adipose tissue D2 activity since thyroid and liver D1 activity were low or normal in the STS and LTS respectively in stressed rats compared to control. Antidepressant study revealed that fluoxetine treatment (10mg/kg po during four weeks) fully reversed stress-induced behavior and normalized serum T4, but not T3 levels and hypercorticosteronemia in stressed group compared to control. The current work adds new concepts concerning TH metabolism changes induced by social stress and suggests that serotonergic system impairment may take part in the key events which ultimately lead to hypothyroxinemia and behavioral changes induced by chronic social defeat. This article is part of a Special Issue entitled 'Anxiety and Depression'.
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