Time-course of serotonin transporter occupancy by single dose of three SSRIs in human brain: A positron emission tomography study with [11C]DASB

• Time-courses of SERT occupancy of three SSRIs were measured.
• 10 and 20 mg escitalopram and 50 mg sertraline showed high and sustained occupancy.
• 20 mg paroxetine showed relatively low and rapidly decreasing occupancy.
• This discrepancy may be related to the single-dosing schedule.
• These drugs and doses would be sufficient for the treatment of depression.

Sixteen healthy volunteers were enrolled and divided into four groups according to the single administration of 10 mg or 20 mg escitalopram, 50 mg sertraline, or 20 mg paroxetine. Four positron emission tomography scans with [11C]DASB were performed on each subject, the first prior to taking the drug, followed by the others at 4, 24, and 48 h after. Serotonin transporter occupancies of the drugs at each time point were calculated. All drugs showed maximum occupancy at 4 h after dosing and then decreasing occupancies with time. Escitalopram and sertraline showed high occupancies of 69.1–77.9% at 4 h, remaining at 52.8–57.8% after 48 h. On the other hand, paroxetine showed relatively low occupancy of 44.6%, then decreasing to 10.3% at 48 h. Escitalopram (both 10 mg and 20 mg) and sertraline (50 mg) showed high and sustained occupancy. Paroxetine (20 mg) showed relatively low and rapidly decreasing occupancy, possibly due to the low plasma concentration by single dosing schedule. Applying the reported concentration of multiple dosing, 20 mg paroxetine will induce over 80% occupancy. The present study suggested that these drugs and doses would be sufficient for the treatment of depression.