Beyond Lithium in the Treatment of Bipolar Illness

Post, Robert M.

doi:10.1016/s0893-133x(98)00020-7

Cited by 75 publications

(36 citation statements)

References 96 publications

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“…1,2 In this regard, adjunctive use of levothyroxine (L-T 4 ) at supraphysiological doses offers promise for patients who suffer rapid cycling [3][4][5][6] and prophylaxis-resistant bipolar disorders, [6][7][8][9] for patients with bipolar and unipolar disorder during a phase of refractory major depressive episode, 10 and patients with refractory chronic depression and dysthymia. 11 Despite knowledge of the role of thyroid hormones in the maturation and the differentiation of the brain, 12,13 and the association between thyroid status and behavioral disturbances in thyroid disease, 14,15 the action of thyroid hormones in the adult brain has received comparatively little attention.…”

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confidence: 99%

“…[16][17][18] Recent studies of the mature mammalian brain have begun to change this situation, 13,[19][20][21][22][23] with new evidence suggesting that thyroid hormones are critically important in maintaining the optimal level of metabolic activity in the mature brain. 20,[24][25][26] For example, hypothyroid adult rats exhibit deficits in 2-deoxy-D [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]glucose uptake by most brain regions, indicating a general cerebral metabolic deficiency. 27 In addition, serum TSH (inversely related to thyroid hormone levels) is inversely related to cerebral metabolism and blood flow in the dorsolateral and mesial prefrontal cortices of human euthyroid patients with major depression.…”

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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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“…In view of that, other ACs started to be tested with success, including carbamazepine, oxcarbazepine, gabapentin, lamotrigine, among others (Post et al, 1998;Moreno et al, 2004;Muzina et al, 2005). In addition to ACs, some atypical antipsychotics (AAPs) were also introduced for the treatment of BD concomitant with the use of mood stabilizers for acute mania or its moderate/severe states (Perlis, 2007;Fountoulakis et al, 2016) as well as for depressive episodes (Fountoulakis et al, 2005).…”

Section: Treatments Available For Bipolar Disordermentioning

confidence: 99%

Kinins and microglial responses in bipolar disorder: a neuroinflammation hypothesis

Naaldijk¹,

Bittencourt²,

Sack

et al. 2016

Biological Chemistry

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Bipolar disorder (BD) is a severe psychiatric disorder that affects up to 15% of the worldwide population. Characterized by switches in mood between mania and depression, its etiology is still unknown and efforts have been made to elucidate the mechanisms involved in first episode, development and progression of the disorder. Microglia activation, abnormal activity of GSK-3β and reduction in neurotrophic factor expression related to neuroinflammatory processes have been indicated to be part of the disorder's pathophysiology. Lithium, the main mood stabilizer used for the treatment and prevention of relapses, acts as an anti-inflammatory agent. Based on that, here we suggest a neuroinflammatory pathway for would be BD progression, in which microglia activation states modulated via constitutive induction of kinin-B1 receptor and reduction of kinin-B2 receptor expression and activity.

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“…There is growing recognition that prophylactic treatment of affective disorders may be inadequate in a substantial proportion of patients (Post et al 1998). Psychiatrists in private practice, as well as in academic referral centers and research settings, increasingly observe patients with mood disorders that respond inadequately to mood stabilizing drugs (Frye et al 2000).…”

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confidence: 99%

Supraphysiological Doses of L-Thyroxine in the Maintenance Treatment of Prophylaxis-Resistant Affective Disorders

Bauer

Berghöfer

Bschor³

et al. 2002

Neuropsychopharmacology

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Beyond Lithium in the Treatment of Bipolar Illness

Abstract: Dramatic changes have recently occurred in the availability

Cited by 75 publications

References 96 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

Kinins and microglial responses in bipolar disorder: a neuroinflammation hypothesis

Supraphysiological Doses of L-Thyroxine in the Maintenance Treatment of Prophylaxis-Resistant Affective Disorders

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