title: Serotonin transporter occupancy of high-dose selective serotonin reuptake inhibitors during major depressive disorder measured with [11C]DASB positron emission tomography.
abstract: BACKGROUND
  Previous work has shown 80% serotonin transporter (5-HTT) occupancy to be a consistent finding at the minimum therapeutic dose during selective serotonin reuptake inhibitor (SSRI) treatment. [(11)C]N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine positron emission tomography ([(11)C]DASB PET) is currently the best method available to quantify 5-HTT occupancy in humans.
  
  
  OBJECTIVE
  The purpose of the present study is to determine 5-HTT occupancy during high dose SSRI treatment using [(11)C]DASB PET.
  
  
  METHODS
  Twelve healthy subjects and 12 subjects with major depressive disorder completed the protocol. Depressed subjects received one [(11)C]DASB PET scan after a minimum of 4 weeks treatment at high doses of venlafaxine, sertraline, or citalopram. Baseline 5-HTT binding potential (BP) was taken as the average 5-HTT BP of the 12 healthy subjects.
  
  
  RESULTS
  Mean striatal 5-HTT occupancy for each antidepressant group was approximately 85% at high therapeutic dose. This was significantly greater than 80% (one-sample t test; p < 0.04, venlafaxine group; p < 0.02, sertraline group; p < 0.01, citalopram group) for each high dose antidepressant group.
  
  
  CONCLUSIONS
  Significantly greater 5-HTT blockade at high dose provides a rationale for raising the dose from the minimum therapeutic dose in specific clinical circumstances. It is likely that 15% unoccupied 5-HTT remains, which should be addressed in future drug development.
authors.affiliation: Clarke site, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, ON, M5T 1R8, Canada.
authors.forename: Aristotle N
authors.initials: AN
authors.lastname: Voineskos
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Anahita
authors.initials: A
authors.lastname: Boovariwala
authors.forename: Sandra
authors.initials: S
authors.lastname: Sagrati
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Pablo
authors.initials: P
authors.lastname: Rusjan
authors.forename: Stephen
authors.initials: S
authors.lastname: Sokolov
authors.forename: Edgar P
authors.initials: EP
authors.lastname: Spencer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ginovart
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology; D003342:Corpus Striatum; D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D020280:Sertraline / Q000008:administration & dosage / Q000494:pharmacology; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D003511:Cyclohexanols; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D000069470:Venlafaxine Hydrochloride