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Closed Access item Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists

Authors:Artigas, Francesc
Romero, Luz
Montigny, Claude de
Blier, Pierre
Keywords:Antidepressants, Dorsal raphe nucleus, Hippocampus, Dindolol, Serotonin, 5-HT1a antagonists
Issue Date:Sep-1996
Citation:Trends in Neurosciences 19 (9) : 378-383 (1996)
Abstract:At clinically relevant doses, selective serotonin (5-HT) reuptake inhibitors (SSRIs) and MAO inhibitors (MAOIs) increase the extracellular concentration of 5-HT in the midbrain raphé nuclei, thereby activating inhibitory somatodendritic 5-HT1A autoreceptors. Consequently, the firing activity of 5-HT neurons is reduced and the enhancement of extracellular 5-HT concentration in forebrain is dampened. Overriding this feedback by using antagonists of 5-HT1A autoreceptors permits SSRIs to produce a marked increase of extracellular 5-HT in the forebrain. Hence, combined treatment with an SSRI and a 5-HT1A antagonist increases the extracellular concentration of 5-HT more so than the former drug alone. The treatment of patients with major depression using an SSRI and pindolol, a 5-HT1A/β-adrenoceptor antagonist, markedly reduced the latency of the antidepressant response in previously untreated patients and induced a rapid improvement in treatment-resistant patients.
Publisher version (URL):http://dx.doi.org/10.1016/S0166-2236(96)10037-0
E-ISSNmetadata.dc.identifier.doi = DOI:1878-108X
Appears in Collections:(IIBB) Artículos

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