title: Brain 5-HT neurotransmission during paroxetine treatment.
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.
  
  
  METHODS
  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.
authors.affiliation: Warneford Hospital, Oxford.
authors.forename: P A
authors.initials: PA
authors.lastname: Sargent
authors.forename: D J
authors.initials: DJ
authors.lastname: Williamson
authors.forename: P J
authors.initials: PJ
authors.lastname: Cowen
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000627:therapeutic use*; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016037:Single-Blind Method; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D006854:Hydrocortisone; D017374:Paroxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors