title: Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients recovered on paroxetine.
abstract: 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.
authors.affiliation: Psychopharmacology Unit, School of Medical Sciences, University of Bristol, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bell
authors.forename: Sam
authors.initials: S
authors.lastname: Forshall
authors.forename: Mariona
authors.initials: M
authors.lastname: Adrover
authors.forename: Jon
authors.initials: J
authors.lastname: Nash
authors.forename: Sean
authors.initials: S
authors.lastname: Hood
authors.forename: Spilios
authors.initials: S
authors.lastname: Argyropoulos
authors.forename: Ann
authors.initials: A
authors.lastname: Rich
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D000368:Aged; D000379:Agoraphobia / Q000188:drug therapy / Q000523:psychology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D017374:Paroxetine / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D014364:Tryptophan / Q000097:blood / Q000502:physiology*
chemical_list: D005442:Flumazenil; D018757:GABA Modulators; D017374:Paroxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan