Serotonin transporter occupancy of high-dose selective serotonin reuptake inhibitors during major depressive disorder measured with [11C]DASB positron emission tomography.
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.
Voineskos
Aristotle N
AN
Clarke site, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, ON, M5T 1R8, Canada.
Wilson
Alan A
AA
Boovariwala
Anahita
A
Sagrati
Sandra
S
Houle
Sylvain
S
Rusjan
Pablo
P
Sokolov
Stephen
S
Spencer
Edgar P
EP
Ginovart
Nathalie
N
Meyer
Jeffrey H
JH
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
D000928:Antidepressive Agents; D015283:Citalopram; D003511:Cyclohexanols; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D000069470:Venlafaxine Hydrochloride