37-39 It has been suggested30 that blunted TRH-induced TSH stimulation might reflect downregulation of the TRH receptors in the pituitary gland secondary to a prolonged increase in hypothalamic TRH

stimulation. Furthermore, the shift to higher iodothyronine levels in euthyroid depressed inpatients, both in Inhibitors,research,lifescience,medical the morning40 and in the evening,37 may contribute to the blunting of TSH response to TRH.41,42 Predictive value of the TRH test So far, studies of the therapeutic predictive value of the TSH response to TRH test have yielded conflicting results.30,43 Some studies have found that the normalization of the test is associated with remission, in which case the blunted TSH response – and more obviously the reduced ΔTSH values- may be considered as a “state” marker of depression.38 Conversely, persistence of blunted responses during remission could represent a “vulnerability” marker to depression. Some investigators43 Inhibitors,research,lifescience,medical have found no link between the initial status of the TRH test and the subsequent response to a particular antidepressant Tipifarnib Transferase inhibitor treatment defined according to its biochemical

mechanism of action. Others44 have found an association between the blunted TSH response Inhibitors,research,lifescience,medical and the response to desipramine (which shows a predominant “noradrenergic” action). On the other hand, it has been observed that patients with the lowest pretreatment evening TSH secretion

(basal and after 11 pm TRH stimulation) have the lowest rate of antidepressant response, and this may contribute to antidepressant treatment resistance.38 In such cases, it has been speculated that adjunction of thyroid hormones,45 Inhibitors,research,lifescience,medical could be particularly beneficial to amplify antidepressant effects, since, by increasing the negative feedback on the hypothalamus, thyroid hormones may decrease Inhibitors,research,lifescience,medical TRH overproduction at this level. To date, only one study has examined the relationship between morning and evening TSH and prolactin (PRL) response to TRH tests prior to antidepressant treatment and 12-month outcome.46 Batimastat In this study, dissociation between 11 pm TRH-induced TSH and PRL stimulation (ie, blunted TSH response associated with normal PRL response) was indicative of poor clinical outcome. Thus, normal PRL response to TRH, despite decreased TRH receptor responsiveness, might reflect a decrease in dopaminergic tone, since dopamine (DA) inhibits PRL secretion. In such patients, one may hypothesize that adjunctive therapy with DA selleck inhibitor agonists might be useful to amplify antidepressant effects. Effects of antidepressants on the HPT axis A number of reports suggest that treatment with antidepressant drugs leads to changes in thyroid function tests: either decreased peripheral thyroid hormone levels and/or increased TSH levels (basal or post-TRH stimulation).