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Brain 5-HT neurotransmission during paroxetine treatment

Published online by Cambridge University Press:  03 January 2018

P. A. Sargent ,
D. J. Williamson  and
P. J. Cowen
P. A. Sargent
Affiliation:
Warneford Hospital, Oxford
D. J. Williamson
Affiliation:
Warneford Hospital, Oxford
P. J. Cowen*
Affiliation:
Warneford Hospital, Oxford
*
Professor P. J. Cowen, Psychopharmacology Research Unit, Warneford Hospital. Headington, Oxford OX3 7JX. Fax: 01865 251076
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Abstract

Background

Animal experimental studies suggest that repeated administration of selective serotonin reuptake inhibitors (SSRIs) produces complex adaptive changes in brain serotonin (5-HT) pathways. The effect of these adaptive changes on different aspects of brain 5-HT neurotransmission and their clinical consequences are not well understood.

Method

We studied the effect of repeated administration of the SSRI, paroxetine (20 mg daily), on the Cortisol responses to the 5-HT precursor, 5-hydroxytryptophan (5-HTP), in healthy subjects and depressed patients.

Results

In healthy subjects, following one week of paroxetine treatment there was a large increase in the Cortisol response to 5-HTP. This increase had all but disappeared following 3 weeks treatment. In contrast, in depressed patients treated with paroxetine for 8 weeks, the Cortisol response to 5-HTP was significantly increased.

Conclusions

SSRI treatment in depressed patients produces a persistent increase in the Cortisol response to 5-HTP, a probable measure of neurotransmission at central 5-HT2 receptors. Potentiation of 5-HT2 neurotransmission is unlikely to account for the efficacy of SSRIs in major depression but might underlie their actions in obsessive–compulsive disorder and also perhaps certain of their adverse effects, notably sexual dysfunction.

Type
Papers
Information
The British Journal of Psychiatry , Volume 172 , Issue 1 , January 1998 , pp. 49 - 52
Copyright
Copyright © 1998 The Royal College of Psychiatrists 

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