This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Bell, C. Articles by Nutt, D. J. Search for Related Content PubMed PubMed Citation Articles by Bell, C. Articles by Nutt, D. J. Social Bookmarking                         What's this?

Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients recovered on paroxetine

Sam Forshall

Mariona Adrover

Jon Nash

Sean Hood

Spilios Argyropoulos

Ann Rich

Psychopharmacology Unit, School of Medical Sciences, University of Bristol, Bristol, UK

David J. Nutt

Department of Psychopharmacology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK

The neurobiological basis of panic disorder has not been clearly established, although a role for serotonin (5-HT) has been postulated. It is clear that drugs which increase 5-HT neurotransmission are effective in treating the condition but how they do so remains a point of debate. The aim of this study was to determine if lowering brain serotonin activity using the technique of tryptophan depletion provoked a short-term relapse of panic symptoms in patients with panic disorder who had responded to drug treatment. Fourteen patients with panic disorder who had responded to treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind crossover design. In addition, they received an infusion of flumazenil (used as a pharmacological challenge) and placebo on each day. The tryptophan depleted drink produced an 87% reduction in plasma tryptophan concentration. Flumazenil produced a panic attack (defined by changes in the panic inventory) in seven out of 14 patients when tryptophan depleted and one out of 14 on the control day (p < 0.02). Three patients also experienced temporary depressive symptoms when tryptophan depleted, with no mood changes being seen on the control days. We conclude that rapid lowering of brain serotonin function can allow the precipitation of panic symptoms in response to flumazenil in panic disorder patients who have responded to treatment with an SSRI. This implies that in panic disorder increased 5-HT availability is important in maintaining the response to SSRIs.

Key Words: 5HT • flumazenil • panic disorder • SSRIs • tryptopha • depletion

Journal of Psychopharmacology, Vol. 16, No. 1, 5-14 (2002)
DOI: 10.1177/026988110201600116


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S Hood, G O'Neil, and G Hulse The role of flumazenil in the treatment of benzodiazepine dependence: physiological and psychological profiles J Psychopharmacol, June 1, 2009; 23(4): 401 - 409. [Abstract] [PDF]

				J. R. Nash, P. A. Sargent, E. A. Rabiner, S. D. Hood, S. V. Argyropoulos, J. P. Potokar, P. M. Grasby, and D. J. Nutt Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study The British Journal of Psychiatry, September 1, 2008; 193(3): 229 - 234. [Abstract] [Full Text] [PDF]

				J. E. Bailey, A. Kendrick, A. Diaper, J. P. Potokar, and D. J. Nutt A validation of the 7.5% CO2 model of GAD using paroxetine and lorazepam in healthy volunteers J Psychopharmacol, January 1, 2007; 21(1): 42 - 49. [Abstract] [PDF]

				R. Mossner, C. M. Freitag, L. Gutknecht, A. Reif, R. Tauber, P. Franke, J. Fritze, G. Wagner, G. Peikert, B. Wenda, et al. The novel brain-specific tryptophan hydroxylase-2 gene in panic disorder J Psychopharmacol, July 1, 2006; 20(4): 547 - 552. [Abstract] [PDF]

				K. Schruers and E. Griez The effects of tianeptine or paroxetine on 35% CO2 provoked panic in panic disorder J Psychopharmacol, December 1, 2004; 18(4): 553 - 558. [Abstract] [PDF]

				D. N. D'Souza, Y. Zhang, F. Garcia, G. Battaglia, and L. D. Van de Kar Fluoxetine-induced changes in body weight and 5-HT1A receptor-mediated hormone secretion in rats on a tryptophan-deficient diet Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R390 - R397. [Abstract] [Full Text] [PDF]