[Contributions of pharmacology in the treatment of resistance to antidepressive agents].
Pharmacology can contribute in four ways to our understanding and to the management of resistant depression: 1) Dosage: some antidepressants have an inverted-U dose-response curve, i.e. the response disappears when dosage is increased. In man, dose-response relationships are not well established because the curves are obtained with groups of patients and they reflect an overall mean rather than the reality of each individual patient. 2) Secondary regulatory adaptive mechanism such as: down regulation of beta, 5-HT2, alpha-2 receptors--increased reactivity of 5-HT1A, alpha-1 and dopaminergic systems. Defective development of these mechanisms is thought to originate resistance in certain cases, which could therefore be corrected more or less specifically by adding thyroid hormone, lithium, an alpha-2 agonist or even by switching to a 5-HT1A agonist or a dopaminergic drug. 3) Biological resistance factors: it has been shown in the rat that hypothyroidism, diabetes, weight loss cause a decrease in beta-adrenergic system reactivity, and therefore a resistance to noradrenergic antidepressants. 4) Co-prescription: the efficacy of noradrenergic antidepressants is known to involve the activation of beta-adrenergic receptors. Animal studies have shown that the co-prescription of a beta-blocker nullifies this efficacy. Benzodiazepines decrease serotonergic and noradrenergic neuronal activity: animal studies have shown that they antagonize most antidepressants. What happens in depressed humans who are often co-prescribed these drugs? I would like to share with you a few data from experimental pharmacology which may help us to think differently, not when faced to a patient with resistant depression, but when confronted with the failure of a well conducted antidepressant treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Puech
A
A
Hôpital de la Salpêtrère, Paris.
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002908:Chronic Disease; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D006728:Hormones / Q000097:blood; D006801:Humans; D017981:Receptors, Neurotransmitter / Q000187:drug effects
D000928:Antidepressive Agents; D006728:Hormones; D017981:Receptors, Neurotransmitter
Apports de la pharmacologie dans l'approche des résistances aux traitements antidépresseurs.