Does Thyroid Supplementation Accelerate Tricyclic Antidepressant Response? A Review and Meta-Analysis of the Literature

Altshuler, Lori L.; Bauer, Michael; Frye, Mark A.; Gitlin, Michael; Mintz, Jim; Szuba, Martin P.; Leight, Kristin; Whybrow, Peter C.

doi:10.1176/appi.ajp.158.10.1617

Cited by 210 publications

(123 citation statements)

References 43 publications

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“…Only women were studied here because previous work has indicated that women benefit more than do men from thyroid hormone supplementation. [39][40] On the basis of previous findings from functional PET studies in bipolar depression, we hypothesized that patients with bipolar depression would have lower relative activity in the middle frontal gyri (within the DLPFC) 35 and the region described by Drevets et al 34 as subgenual prefrontal cortex (here renamed more descriptively as the subgenual cingulate cortex), and higher activity in subcortical and limbic structures 36 compared to healthy controls. We further hypothesized that adjunctive L-T 4 treatment would improve mood in bipolar depressed patients, and that clinical improvement would be associated with increased activity in the prefrontal cortex and decreased activity in limbic and subcortical structures, including the basal ganglia and thalamus.…”

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Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression

et al. 2005

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Supplementation of standard treatment with high-dose levothyroxine (L-T 4 ) is a novel approach for treatment-refractory bipolar disorders. This study tested for effects on brain function associated with mood alterations in bipolar depressed patients receiving high-dose L-T 4 treatment adjunctive to ongoing medication (antidepressants and mood stabilizers). Regional activity and whole-brain analyses were assessed with positron emission tomography and [ 18 F]fluorodeoxyglucose in 10 euthyroid depressed women with bipolar disorder, before and after 7 weeks of open-label adjunctive treatment with supraphysiological doses of L-T 4 (mean dose 320 lg/day). Corresponding measurements were acquired in an age-matched comparison group of 10 healthy women without L-T 4 treatment. The primary biological measures were relative regional activity (with relative brain radioactivity taken as a surrogate index of glucose metabolism) in preselected brain regions and neuroendocrine markers of thyroid function. Treatment-associated changes in regional activity (relative to global activity) were tested against clinical response. Before L-T 4 treatment, the patients exhibited significantly higher activity in the right subgenual cingulate cortex, left thalamus, medial temporal lobe (right amygdala, right hippocampus), right ventral striatum, and cerebellar vermis; and had lower relative activity in the middle frontal gyri bilaterally. Significant behavioral and cerebral metabolic effects accompanied changes in thyroid hormone status. L-T 4 improved mood (remission in seven patients; partial response in three); and decreased relative activity in the right subgenual cingulate cortex, left thalamus, right amygdala, right hippocampus, right dorsal and ventral striatum, and cerebellar vermis. The decrease in relative activity of the left thalamus, left amygdala, left hippocampus, and left ventral striatum was significantly correlated with reduction in depression scores. Results of the whole-brain analyses were generally consistent with the volume of interest results. We conclude that bipolar depressed patients have abnormal function in prefrontal and limbic brain areas. L-T 4 may improve mood by affecting circuits involving these areas, which have been previously implicated in affective disorders. Molecular Psychiatry (2005) 10, 456-469.

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Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression

et al. 2005

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“…Another meta-analysis by Altshuler et al [33] found that in five of six studies, T3 was significantly more effective than placebo in accelerating clinical response to TCAs in nonrefractory depression (weighted effect size index = 0.58). They also found that women were more likely than men to benefit from this strategy.…”

Section: Level 2: Triiodothyroninementioning

confidence: 99%

Evidence for the Benefits of Nonantipsychotic Pharmacological Augmentation in the Treatment of Depression

Chang

Sato²,

Han

2013

CNS Drugs

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Failure to achieve an adequate response after initial antidepressant treatment in patients with depression is common and remains a clinical challenge. In recent years, some atypical antipsychotic agents have been approved by the US Food and Drug Administration for use in an augmentation strategy for major depressive disorder, and other agents are already in common use in clinical practice. We conducted a search of MEDLINE for relevant studies of augmentation strategies using randomized controlled trials and meta-analyses, and we summarize and discuss the various agents other than atypical antipsychotics. Lithium and thyroid hormone augmentation may improve the response of tricyclic antidepressants but not that of selective serotonin reuptake inhibitors. The efficacy of augmentation with modafinil, buspirone, methylphenidate, folic acid, pindolol and lamotrigine is limited or equivocal. Most of the studies have not focused on treatment-resistant depression (TRD). More trials are needed to help develop evidence-based options for augmentation in TRD.

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“…Thyroid hormones (TH) have a profound influence on behavior and mood, and appear to be capable of modulating the phenotypic expression of major affective illness 3,4,5,6 . Thyroid supplementation is now widely accepted as an effective treatment option for patients with affective disworders 7,8,9 .…”

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The Relationships between Thyroid Hormones and the Brain Serotonin (5-HT) System and Mood: Of Synergy and Significance in the Adult Brain- A Review

Rahman

Ali²

2015

Faridpur Med Coll J

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Abstract:The use of thyroid hormones as an effective adjunct treatment for affective disorders has been studied over the past three decades and has been conformed repeatedly. Interaction of the thyroid and monoamine neurotransmitter systems has been suggested as a potential underline mechanism of action. While catecholamine and thyroid interrelationships have been reviewed in detail, the serotonin system has been relatively neglected. Thus, the goal of this article is to review the literature on the relationship between thyroid hormones and the brain serotonin (5-HT) system. In humans, neuroendocrine challenge studies in hypothyroid patients have shown a reduced 5-HT responsiveness that is reversible with replacement therapy.In the majority of the studies, the effects of thyroid hormone administration in animals will experimentally-induced hypothyroid sates include an increase in cortical 5-HT concentrations and a desensitization of auto inhibitory 5-HT 1A receptors in the rap he area, resulting in disinhibition of cortical hippocampal 5-HT release. Furthermore, there is some indication that thyroid hormones may increase cortical 5-HT 2 receptor sensitivity. In conclusion, there is robust evidence, particularly from animal studies, that the thyroid economy has a modulating impact in the brain serotonin system. Thus it is postulated that one mechanism, among others, through which exogenous thyroid hormones may exert their modulatory effects in affective illness is via an increase in serotonergic neurotransmission, specifically by reducing the sensitivity of 5-HT 1A auto receptors in the raphe area, and by increasing 5-HT 2 receptor sensitivity.

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Does Thyroid Supplementation Accelerate Tricyclic Antidepressant Response? A Review and Meta-Analysis of the Literature

Abstract: This meta-analysis supports the efficacy of T(3) in accelerating clinical response to tricyclic antidepressants in patients with nonrefractory depression. Furthermore, women may be more likely than men to benefit from this intervention.

Cited by 210 publications

References 43 publications

Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression

Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression

Evidence for the Benefits of Nonantipsychotic Pharmacological Augmentation in the Treatment of Depression

The Relationships between Thyroid Hormones and the Brain Serotonin (5-HT) System and Mood: Of Synergy and Significance in the Adult Brain- A Review

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