title: Effects of acute tryptophan depletion in serotonin reuptake inhibitor-remitted patients with generalized anxiety disorder.
abstract: BACKGROUND
  Serotonergic antidepressants [selective serotonin reuptake inhibitor (SSRI)] are first-line treatments for generalised anxiety disorder (GAD); however, it is not known if synaptic serotonin (5-HT) availability is important for SSRI efficacy. The present study tested the hypothesis that temporary reduction in central 5-HT transmission, through acute tryptophan depletion (ATD), would reverse the therapeutic effect of the SSRIs in GAD patients.
  
  
  METHODS
  Twelve patients (six males) with GAD, who showed sustained clinical improvement with SSRI treatment, underwent ATD in a double-blind, placebo-controlled, within-subjects design over 2 days, 1 week apart. At the peak time of depletion, the participants inhaled 7.5% CO2 and air in random order for at least 12 min each. Psychological responses were measured using the Spielberger State Anxiety Inventory (STAI-S) and GAD-symptom visual analogue scales (VASs; e.g., worry and tense) and Profile of Mood States.
  
  
  RESULTS
  Free plasma tryptophan to large neutral amino acid (LNAA) ratio decreased by 92% on the depletion day and decreased by 2% on the control day. Irrespective of depletion condition, 7.5% CO(2) inhalation significantly increased STAI-S and GAD-related VAS scores (all p < 0.05) compared with air inhalation. ATD had no effect on any of these measures despite the substantial reduction in free tryptophan/LNAA ratio.
  
  
  CONCLUSIONS
  Although SSRIs treat GAD effectively, the present results suggest that the mechanism of action is different to that seen in panic, social anxiety, and post-traumatic stress disorders. Successful SSRI treatment of GAD may involve long-term receptor changes or alterations in other neurotransmitter systems downstream of serotonin.
authors: School of Psychiatry and Clinical Neurosciences (M521), University of Western Australia, Perth, Australia, sean.hood@uwa.edu.au.
authors: Sean D
authors: SD
authors: Hood
authors: Dana A
authors: DA
authors: Hince
authors: Simon J C
authors: SJ
authors: Davies
authors: Spilios
authors: S
authors: Argyropoulos
authors: Hayley
authors: H
authors: Robinson
authors: John
authors: J
authors: Potokar
authors: David J
authors: DJ
authors: Nutt
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000339:Affect / Q000187:drug effects; D000596:Amino Acids / Q000008:administration & dosage*; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D001628:Beverages; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000008:administration & dosage*; D004311:Double-Blind Method; D004739:England; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D014364:Tryptophan / Q000097:blood / Q000172:deficiency*; D014904:Western Australia
chemical_list: D000596:Amino Acids; D014151:Anti-Anxiety Agents; D002245:Carbon Dioxide; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan