title: Brain kinetics of paroxetine and fluoxetine on the third day of placebo substitution: a fluorine MRS study.
abstract: OBJECTIVE
  This study tested whether a relationship exists between concentration and response following discontinuation of selective serotonin reuptake inhibitors.
  
  
  METHODS
  Eight patients with remitted major depression who were taking 20 mg/day of either fluoxetine or paroxetine underwent placebo substitution for 3 days. Serum drug and brain fluorine levels were obtained before and after placebo substitution.
  
  
  RESULTS
  With placebo substitution, a mean of 88% (SD=13%) of brain fluorine signal from fluoxetine (plus fluorinated metabolites) remained, compared with a mean of 38% (SD=17%) of the brain fluorine signal from paroxetine (plus fluorinated metabolites). Among patients taking paroxetine, adverse events during placebo substitution correlated highly with steady-state brain drug levels.
  
  
  CONCLUSIONS
  The correlation of clinical effects with brain drug levels in the paroxetine group suggests that relationships between drug response and brain drug concentrations merit further investigation.
authors.affiliation: McLean Hospital, Belmont, MA 02478, USA. mehenry@mclean.harvard.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Henry
authors.forename: C M
authors.initials: CM
authors.lastname: Moore
authors.forename: M J
authors.initials: MJ
authors.lastname: Kaufman
authors.forename: D
authors.initials: D
authors.lastname: Michelson
authors.forename: M E
authors.initials: ME
authors.lastname: Schmidt
authors.forename: E
authors.initials: E
authors.lastname: Stoddard
authors.forename: A J
authors.initials: AJ
authors.lastname: Vuckevic
authors.forename: P J
authors.initials: PJ
authors.lastname: Berreira
authors.forename: B M
authors.initials: BM
authors.lastname: Cohen
authors.forename: P F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005461:Fluorine / Q000378:metabolism*; D005473:Fluoxetine / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017374:Paroxetine / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*
chemical_list: D005461:Fluorine; D005473:Fluoxetine; D017374:Paroxetine; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors