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Potentialisation par les hormones thyroïdiennes des traitements tricycliques et sérotoninergiques dans les dépressions résistantes

Doi : ENC-6-2004-30-3-0013-7006-101019-ART9 

F. Sintzel [1],

M. Mallaret [2],

T. Bougerol [3]

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Résumé

L’émergence d’un nombre non négligeable de tableaux dépressifs résistants aux traitements antidépresseurs disponibles a conduit à de nombreuses recherches ces 30 dernières années. Celles-ci ont porté de façon privilégiée sur le « statut thyroïdien pré-morbide » des patients déprimés résistants à un traitement tricyclique bien mené. Le concept d’anomalies thyroïdiennes « subtiles » sera ainsi mis à jour, tout comme celui d’anomalies thyroïdiennes centrales pouvant échapper à une détection fiable par le biais des dosages plasmatiques. Après avoir exposé les principes pharmacologiques sous-jacents au phénomène de potentialisation des traitements tricycliques et sérotoninergiques par les hormones thyroïdiennes, nous aborderons les modalités pratiques de cette démarche qui, à ce jour, n’a pas encore trouvé sa place dans la pratique quotidienne, faute de consensus reposant sur des études méthodologiquement fiables. Par ailleurs, nous ferons le point sur les travaux récents et encore peu nombreux concernant la potentialisation des antidépresseurs sérotoninergiques par les hormones thyroïdiennes.

Abstract

Potentializing of tricyclics and serotoninergics by thyroid hormones in resistant depressive disorders

In response to the increase of resistant depressive disorders and in spite of improved treatments, numerous studies were conducted in the last thirty years aiming at assessing the pre-morbid thyroid state of depressed patients resistant to well conducted tricyclic treatments. « Minimal » thyroid abnormalities were evidenced as well as central thyroid disorders which may not be detected by peripheral-i.e plasmatic- dosages. Regarding the premorbid thyroid status, the hypothesis of subclinical hypothyroidism was considered by many authors.It is marked by four grades including T3 and T4 decreased levels, basal TSH concentration abnormalities as well as increased TSH response to TRH stimulation, and the presence of antimicrosomal and antithyroglobulin antibodies. Although, there are different views on the existence or not of these abnormalities, we’ll focus our attention on a metaanalysis including six studies.It shows in a population with a resistant depression, 52 % of patients with subclinical hypothyroidism, against 8 to 17 % in patients with simple depression and 5 % in the overall population.Similarly, antithyroid antibody levels (group IV hypothyroidism) were significantly higher in depressed patients (9 % to 20 % against 7,5 % in the overall population). For many years, a central hypothyroidism was hypothesized on the basis of an exhausted T3-T4 transference mechanism and a lowered TRH hypothalamic biodisponibility.In the last years, new data emerged on the role of transthyretin, a cerebral carrier T4 protein, whose concentration in the CSF was found significantly lower in depressed patients than in a control group, the lowest levels being observed in the most severely depressed.This decreased level of transthyretin would result in a lower central T4 biodisponibility-hence, in view of a T4-T3 desiodation insufficiency, a T3 deficit is observed. A low transthyretin level associated or not to subclinical hypothyroidism could be a factor of depressive vulnerability on one hand, of resistance to tricyclic treatment on the other one. Conversely, subclinical hypothyroidism could be a predictive factor of a good response to a potentializing strategy. The pharmacological mechanisms involved in this potentializing phenomenon are now well known : they consist in an interaction between depression, adrenergic receptors and thyroid hormones biodisponibility. The decreased norepinephrine level observed in depressive patients is associated, in case of increased thyroid hormones biodisponibility, with a higher sensitivity of adrenergic receptors, mostly betaadrenergic. This seems to underly the recovery process. According to some authors, the serotoninergic system might be involved in the potentialization of tricyclics by thyroid hormones. We know that in animals with hypothyroidism, the serotonin synthesis is decreased and that the administration of T3 increases the brain levels of serotonin and its 5HIA catabolite. In addition, T3 could correct the down-regulation induced by serotoninergics on beta-adrenergic receptors. On the basis of numerous studies carried out on the potentializing of tricyclics, we suggest practical modalities of treatment – which until today did not materialize in every day practice in the absence of a clear consensus based on statistically reliable data : after four to six weeks of inefficient tricyclic or serotoninergic treatment on a correct dosage testified by plasmatic dosages, it is recommended to initiate a T3 treatment on a effective posology (25 to 50 micrograms per day), which must be reached in 2 or 3 days, except in case of rare and transitory side effects (sweating, shaking, tachycardia, nervousness, anxiety). If the treatment is not rapidly efficient, it must be discontinued in case there is no improvement after 3 weeks. Until today, there is no consensus about the duration of a T3 treatment. It is important to take into account the predictive criteria of good or bad response to a T3 potentialization, since they have direct consequences on the management of depressed patients. For example, a high degree of chronic evolution with resistance to numerous treatments, associated disorders according to the DSM IV axis I and a comorbidity of addiction, point to a bad prognosis of a potentialization treatment. In addition, we’ll examine the few recent studies on the potentializing of serotoninergic antidepressant drugs by thyroid hormones.


Mots clés : Antidépresseurs , Dépression résistante , Hormones thyroïdiennes , Hypothyroïdisme subclinique , Neurotransmission adrénergique , Neurotransmission sérotoninergique , Transthyrétine.

Keywords: Adrenergic neurotransmission , Antidepressants , Resistant depression , Serotoninergic neurotransmission , Subclinical hypothyroidism , Thyroid hormones , Transthyretin.


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© 2004 Elsevier Masson SAS. Tous droits réservés.
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Vol 30 - N° 3

P. 267-275 - juin 2004 Retour au numéro
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