Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: A [C-11]DASB PET imaging study

Objective: Selective serotonin reuptake inhibitors are commonly used to tre at major depression; however, the percentage of serotonin (5-HT) transporte r (5-HTT) sites occupied during clinical dosing is unknown. This study meas ured the proportion of 5-HTT sites blocked during paroxetine and citalopram treatment of depression and assessed the relationship between serum paroxe tine levels and the proportion of 5-HTT sites blocked. Method: Twelve medication-free depressed patients completed a 6-week trial of either paroxetine (N=8) or citalopram (N=4). Striatal 5-HTT binding pote ntial was measured with [C-11]DASB and positron emission tomography, before and after 4 weeks of treatment. The binding potential is proportional to r eceptor 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 fou nd after either treatment, compared to changes found over a 4-week period i n 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 treate d with 20 mg/day of citalopram (N=4), the mean 5-HTT occupancy was 77%. 5-H TT occupancy increased in a nonlinear relationship with serum levels of par oxetine such that a plateau of occupancy around 85% occurred for serum paro xetine levels greater than 28 mug/liter. Conclusions: During treatment with clinical doses of paroxetine or citalopr am, 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 effec ts.