Depression thyroid hormones

The adult brain is endowed with nuclear as well as cytosolic and membrane T3 receptors that have been visualized by autoradiography and studied biochemically [30-33]. Both neurons and neuropil are labeled by [ 1251]T3, and the labeling is selective across brain regions. Functionally, one of the most prominent features of neural action of thyroid hormone in adulthood is subsensitivity to norepinephrine as a result of a hypothyroid state [27], These changes may be reflections of loss of dendritic spines in at least some neurons of the adultbrain. Clinically, thyroid hormone deficiency increases the probability of depressive illness, whereas thyroid excess increases the probability of mania (Ch. 52) in susceptible individuals [27],... 

A number of medical conditions are associated with high rates of depression (see Table 3.4). In some instances, the distinction between MDD and depression due to a general medical condition is largely academic with little bearing on treatment selection. For example, pancreatic cancer may induce depression directly through the release of tumor-secreted substances however, depression in the pancreatic cancer patient is treated with conventional antidepressant medications. In other cases, the diagnostic distinction bears important treatment implications. One commonly cited example is depression occurring in association with hypothyroidism. Patients with depression and hypothyroidism do not respond to antidepressant treatment alone but require a thyroid hormone supplement. 

Triiodothyronine (Cytomel, T3). T3 is also an effective augmenting agent. It is important to use the T3 thyroid hormone instead of thyroxine (T4). T4 is the form most often used to treat hypothyroidism, but T3 crosses from the bloodstream to the brain more easily and thus is better for treating depression. T3 is usually tolerated well and is taken at 25-50 pg/day in split doses. When taking T3, laboratory tests to check thyroid function should be performed periodically. 

Thyroid Hormone (Thyroxine, Synthroid). The most common use of thyroxine in bipolar patients is the treatment of lithium-induced hypothyroidism. Approximately 5% of patients receiving long-term lithium treatment ultimately develop hypothyroidism. When this occurs, the patient with bipolar disorder may present with symptoms of a depressive episode. Therefore, periodic thyroid axis monitoring, that is, a serum thyroid stimulating hormone (TSH) test, is required for all patients taking lithium and should always be performed when the bipolar patient experiences a depressive episode. 

The next step in the management of the depressed bipolar patient is to evaluate thyroid function. This is especially important for patients treated with lithium in order to rule out lithium-induced hypothyroidism. When this occurs, the addition of thyroid hormone replacement may relieve the depressive symptoms without any additional changes to the bipolar treatment regimen. 

Dorn, L.D., Burgess, E.S., Dichek, H.L., Putnam, F.W., Chrousos, G.P., and Gold, P.W. (1996) Thyroid hormone concentrations in depressed and nondepressed adolescents group differences and behavioral relations [see comments]. / Am Acad Child Adolesc Psychiatry 35 299-306. 

The mechanisms by which thyroid hormones enhance antidepressant activity are still unknown. It is of interest that thyroid hormone increases net activity of several neurotransmitters that are putatively involved in the pathophysiology of depression in a way that is descriptively similar to that of estrogens. Receptors for the two hormones belong to the same superfamily. As was previously mentioned [Pfaff 1996], these issues are currently being explored, and clarifications are expected shortly. 

Gorman JM, Hatterer JA TTie role of thyroid hormone in refractory depression, in Refractory Depression Current Strategies and Future Directions. Edited by Nolen WA, Zohar J, Roose SP, et al. Chichester, England, Wiley, 1994, pp 121-128... 

Targum SD, Greenberg RD, Harmon RE, et al Thyroid hormone and the TRH stimulation test in refractory depression. J Chn Psychiatry 45 345-346, 1984 Tariot PN, Cohen RM, Sunderland T L-Deprenyl in Alzheimer s disease. Arch Gen Psychiatry 44 427-433, 1987... 

A common mistake is to treat bipolar depression in the same manner that one treats unipolar depression, overlooking the need for a mood stabilizer. In bipolar depression, the first pharmacological intervention should be to start or optimize treatment with a mood stabilizer rather than to start administering an antidepressant medication. In addition, thyroid function should be evaluated, particularly if the patient is taking lithium. Subclinical hypothyroidism, manifested as an increased thyroid-stimulating hormone level and normal triiodothyronine and thyroxine levels, may present as depression in affectively predisposed individuals. In such cases, the addition of thyroid hormones may be beneficial, even if there is no other evidence of hypothyroidism. 

Thyroid dysregulation has also been reported in depressed patients. Up to 25% of depressed patients are reported to have abnormal thyroid function. These include a blunting of response of thyrotropin to thyrotropin-releasing hormone, and elevations in circulating thyroxine during depressed states. Clinical hypothyroidism often presents with depressive symptoms, which resolve with thyroid hormone supplementation. Thyroid hormones are also commonly used in... 

Thyroid hormones are not effective and can be detrimental in the management of obesity, abnormal vaginal bleeding, or depression if thyroid hormone levels are normal. Anecdotal reports of a beneficial effect of T3 administered with antidepressants were not confirmed in a controlled study. 

Since thyroid illness is commonly associated with depression, especially in women, it has long been observed that treating the thyroid abnormalities also can reverse the depression. This is especially true for treating hypothyroidism with thyroid hormone replacement (either T3 or T4). It has even been observed that giving supplemental thyroid hormone to depressed patients unresponsive to first-line antidepressants but without overt hypothyroidism can boost the antidepressant response of the first-line antidepressant (thyroid combo in Fig. 7—30). Thyroid hormone is also commonly administered to bipolar patients resistant to mood stabilizers, particularly those with rapid cycling (see discussion of combinations for bipolar disorders below). 

Herlihy JT, Stacy C, Bertrand HA. Long-term food restriction depresses serum thyroid hormone concentrations in the rat. Mech Ageing Dev 1990 53 9-16. 

Acute effects of 2,3,7,8-TCDD on thyroid function have been also reported in mice. In contrast with observations in rats, in which 2,3,7,8-TCDD appears to have independent effects on T4 and T3 levels, serum T4 and T3 levels were decreased in a dose-dependent fashion in male C57BL/6J mice 8 days after a single gavage dose of 0.03-235 g 2,3,7,8-TCDD/kg (Weber et al. 1995). A similar effect was observed in male DBA/2J mice treated with a single dose of 1-3,295 g/kg. In C57BL/6J mice, maximum depression of thyroid hormones (35% of controls) was achieved with a dose of 133 g/kg. In male DBA/2J mice, maximum reductions in T3 and T4 levels (40 and 20% of controls, respectively) were attained with the highest dose level (Weber et al. 1995). It should be noted that the Weber et al. (1995) study did not include statistical analysis of the results. 

Other interventions used for refractory bipolar depressed patients include atypical antipsychotics, thyroid hormones, stimulants (often used in the treatment of attention-deficit/hyperactivity disorder), and phototherapy. Repetitive transcraneal magnetic stimulation (rTMS) and vagal nerve stimulation (VNS) are techniques currently being researched. 

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