Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study.
OBJECTIVE
Selective serotonin reuptake inhibitors are commonly used to treat major depression; however, the percentage of serotonin (5-HT) transporter (5-HTT) sites occupied during clinical dosing is unknown. This study measured the proportion of 5-HTT sites blocked during paroxetine and citalopram treatment of depression and assessed the relationship between serum paroxetine levels and the proportion of 5-HTT sites blocked.


METHODS
Twelve medication-free depressed patients completed a 6-week trial of either paroxetine (N=8) or citalopram (N=4). Striatal 5-HTT binding potential was measured with [(11)C]DASB and positron emission tomography, before and after 4 weeks of treatment. The binding potential is proportional to receptor density. Striatal 5-HTT binding potential was measured twice in six healthy subjects and once in 11 healthy subjects.


RESULTS
A significant decrease in striatal 5-HTT binding potential was found after either treatment, compared to changes found over a 4-week period in healthy subjects. For patients treated with 20 mg/day of paroxetine (N=7), the mean proportion of 5-HTT sites occupied was 83%. For patients treated with 20 mg/day of citalopram (N=4), the mean 5-HTT occupancy was 77%. 5-HTT occupancy increased in a nonlinear relationship with serum levels of paroxetine such that a plateau of occupancy around 85% occurred for serum paroxetine levels greater than 28 microg/liter.


CONCLUSIONS
During treatment with clinical doses of paroxetine or citalopram, approximately 80% of 5-HTT receptors are occupied. This change in 5-HTT binding potential is greater than the known physiological range of changes in 5-HTT binding potential but may be necessary for some therapeutic effects.
Meyer
J H
JH
PET Centre, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Ontario, Canada. jmeyer@camhpet.on.ca
Wilson
A A
AA
Ginovart
N
N
Goulding
V
V
Hussey
D
D
Hood
K
K
Houle
S
S
D000328:Adult; D001665:Binding Sites; D001692:Biological Transport / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D017397:Prefrontal Cortex / Q000378:metabolism; D011699:Putamen / Q000378:metabolism; D012044:Regression Analysis; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013788:Thalamus / Q000378:metabolism; D014055:Tomography, Emission-Computed
D015283:Citalopram; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors