Low Plasma Thyroid Indices of Depressed Patients are Attenuated by Antidepressant Drugs and Influence Treatment Outcome

Abstract

Decreased turnover of thyroid indices and blunting of TSH release after TRH administration has been associated with depressive disorder. A further decrease in plasma thyroid hormone; during antidepressant treatment has been reported. However, the putative association between the plasma thyroid indices' concentration and response has not been addressed. In the present study 21 depressed inpatients underwent a four-week double blind antidepressant with amitriptyline and mianserin; their plasma thyroid hormone indices (total thyroxine [TT4], free thyroxine [FT4], total triiodothyronine [TT3], free triiodothyronine [FT3], thyrotropin [TSH], and thyroglobulin [TBG]) were quantified to elucidate their involvement in depression and during antidepressant drug treatment. Depressed patients' plasma TSH, when corrected for age, was significantly lower than that of healthy subjects. During antidepressant treatment the entire patient cohort showed a significant decrease in plasma TT4 and FT4 concentrations. Responders showed a significant drop in TT4 FT4, FT3, and T4/TBG, but nonresponders only a decrease in FT4. During mianserin treatment, a decrease was observed in TT4, FT4, FT3, and T4/TBG. FT4 and FT3 baseline levels correlated positively with the improvement in the Hamilton Depression Rating Score (HDRS). These findings show that depressed inpatients' serum TSH levels are within the reference range, but significantly lower than those of healthy subjects, and those patients who turn out to be nonresponders have potentially lower availability of thyroid hormones than responders. Therefore, we hypothesize that in order to assure clinical improvement in depression, an adequate capacity of the thyroid hormone pool is necessary to compensate for the additional antidepressant-provoked decrease in serum thyroid hormone availability.

Thyrotropin, but not a polymorphism in type II deiodinase, predicts response to paroxetine in major depression

“…Other studies measuring TSH in the morning did not find such a relation (8)(9)(10)(11)(12). We only found a significant association after exclusion of patients with positive TPO titers.…”

“…So far, the nature of a relation between thyroid function and response seems unclear; Duval et al (6) described higher evening TSH concentrations in treatment responders, while Sullivan et al (7) found that non-response was predicted by a high delta TSH in the TRH test. However, most studies were retrospective and included only small groups of patients (6,(9)(10)(11)(12). Furthermore, no studies so far included TPO antibodies in their analysis, although thyroid autoimmunity is an important determinant of TSH levels (13) or may be a predictor of response itself.…”

Thyroid Function and Mental Disorders: An Insight into the Complex Interaction

“…A number of previous studies have suggested that the thyroid function of depressed patients was within the normal range, while in overt thyroid dysfunction, it was extremely uncommon [12][13][14]. It has been reported that most of the patients with depression may have alterations in their thyroid functions, which include a slight elevation in the serum T4 level, a blunted TSH response to the TRH stimulation and loss of the nocturnal TSH rise.…”

Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors

“…Some studies report an association of clinical and sublinical hypothyroidism with reduced response to antidepressant treatment (Berlin et al, 1999;Corruble et al, 2004) but this is not consistently supported (Iosifescu et al, 2001;Joffe, 1999). Several changes have been reported in the thyroid function of depressed patients treated with antidepressants but their direction is not consistent (Gambi et al, 2005;Rao et al, 1996;Sagud et al, 2002). An association with response to treatment has been reported (Gendall et al, 2003;Shelton et al, 1993).…”