Hostname: page-component-76fb5796d-qxdb6 Total loading time: 0 Render date: 2024-04-29T14:12:51.643Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access Rights & Permissions [Opens in a new window]

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 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Anderson, I. M. & Tomenson, B. M. (1994) The efficacy of selective serotonin re-uptake inhibitors in depression: a meta-analysis of studies against tricyclic antidepressants. Journal of Psychopharmacology. 8, 238–249.CrossRefGoogle ScholarPubMed
Arnott, S. & Nutt, D. (1994) Successful treatment of fluvoxamine-induced anorgasmia by cyproheptadine. British Journal of Psychiatry, 164, 838–839.CrossRefGoogle ScholarPubMed
Blier, P. & de Montigny, C. (1994) Current advances and trends in the treatment of depression. Trends in Pharmacological Sciences, 15, 220–226.CrossRefGoogle ScholarPubMed
Conover, W. J. & Iman, R. L. (1981) Rank transformations as a bridge between parametric and non-parametric statistics. American Statistician, 35, 124–129.Google Scholar
Cowen, P. J. (1993) Serotonin receptor subtypes in depression: evidence from studies in neuroendocrine regulation. Clinical Neuropharmacology, 16 (suppl. 3), S6–S18.Google ScholarPubMed
Deakin, J. F. W. & Graeff, F. G. (1991) 5-HT and mechanisms of defence. Journal of Psychopharmacology, 5, 305–315.CrossRefGoogle ScholarPubMed
Erzegovesi, S., Ronchi, P. & Smeraldi, E. (1992) 5-HT-2 receptor and fluvoxamine effect in obsessive compulsive disorder. Human Psychopharmacology, 7, 287–289.CrossRefGoogle Scholar
Fuller, R. W. (1981) Serotonergic stimulation of pituitary-adrenocortical function in rats. Neuroendocrinology, 32, 118–127.CrossRefGoogle ScholarPubMed
Gartside, S. E. & Cowen, P. J. (1990) Mediation of ACTH and prolactin responses to 5-HTP by 5-HT2 receptors. European Journal of Pharmacology, 179, 103–109.CrossRefGoogle Scholar
Gartside, S. E., Cowen, P. J. & Sharp, T. (1992) Effect of 5-hydroxy-L-tryptophan on the release of 5-HT in rat hypothalamus in vivo as measured by microdialysis. Neuropharmacology, 31, 9–14.CrossRefGoogle ScholarPubMed
Jenck, F., Moraeu, J.-L., Mutel, V., et al (1993) Evidence for a role of 5-HTIC receptors in the antiserotonergic properties of some antidepressant drugs. European Journal of Pharmacology, 231, 223–229.CrossRefGoogle Scholar
Johnson, A. M. (1991) The comparative pharmacological properties of selective serotonin re-uptake inhibitors in animals. In Selective Serotonin Re-uptake Inhibitors (eds Feighner, J. P. & Boyer, W. F.), pp. 37–70. Chichester: Wiley.Google Scholar
Katsuda, Y., Walsh, A. E. S., Ware, C. J., et al (1993) Meta-chlorophenylpiperazine decreases slow-wave sleep in humans. Biological Psychiatry, 33, 49–51.CrossRefGoogle ScholarPubMed
Lee, M. A., Nash, J. F., Barnes, M., et al (1991) Inhibitory effect of ritanserin on the 5-hydroxytryptophan-mediated Cortisol. ACTH and prolactin secretion in humans. Psychopharmacology, 103, 258–264.CrossRefGoogle ScholarPubMed
Meltzer, H. Y., Lowy, M., Robertson, A., et al (1984) Effect of 5-hydroxytryptophan on serum Cortisol levels in major affective disorders. 3. Effects of antidepressants and lithium carbonate. Archives of General Psychiatry, 41, 391–397.CrossRefGoogle Scholar
Meitzer, H. Y., & Maes, M. (1994) Effects of pindolol on the L-5-HTP-induced increase in plasma prolactin and Cortisol concentrations in man. Psychopharmacology, 114, 635–643.CrossRefGoogle Scholar
Piccinelli, M., Pini, S., Bellantuono, C., et al (1995) Efficacy of drug treatment in obsessive–compulsive disorder: a meta-analytic review. British Journal of Psychiatry, 166, 424–443.CrossRefGoogle ScholarPubMed
Preskom, S. H. (1995) Comparison of the tolerability of bupropion, fluoxetine, imipramine. nefazodone, paroxetine, sertraline and venlafaxine. Journal of Clinical Psychiatry, 56 (suppl. 6), 12–21.Google Scholar
Price, L. H., Chantey, D. S., Delgado, P. L., et al (1989) Effects of desipramine and fluvoxamine treatment on the prolactin response to tryptophan: serotonergic function and the mechanism of antidepressant action. Archives of General Psychiatry, 46, 625–631.CrossRefGoogle ScholarPubMed
Thompson, C., Mezey, G., Corn, T., et al (1985) The effect of desipramine on melatonin and Cortisol secretion in depressed and normal subjects. British Journal of Psychiatry, 147, 389–393.CrossRefGoogle ScholarPubMed
Yatham, L. N. & Steiner, M. (1993) Neuroendocrine probes of serotonergic function: a critical review. Life Sciences. 53, 447–463.CrossRefGoogle ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.