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Trends Neurosci. 1996 Sep;19(9):378-83.

Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists.

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  • 1Dept of Neurochemistry Instituto de Investigaciones Biomédicas de Barcelona (CSIC), Spain.

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/ beta-adrenoceptor antagonist, markedly reduced the latency of the antidepressant response in previously untreated patients and induced a rapid improvement in treatment-resistant patients.

PMID:
8873352
[PubMed - indexed for MEDLINE]
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