Randomized, quadruple-blind PET study (n≈74) comparing (S)-ketamine 0.25 mg/kg i.v. vs saline to assess ketamine binding to SERT with [11C]DASB in severe depression.
This study uses [11C]DASB PET to measure serotonin transporter binding after intravenous ketamine (multiple substudies including a main randomized double-blind esketamine vs saline comparison and several pilot dosing regimens of R,S- and S-ketamine).
Outcomes include PET SERT binding measures and the relationship between ketamine-induced SERT changes and antidepressant efficacy in severely depressed patients; multiple dosing regimens include bolus+infusion and single infusions timed before PET acquisition.
Esketamine infusion (main study) 0.25 mg/kg i.v. vs saline, single infusion before PET.
0.25 mg/kg i.v. infusion over 40 minutes (ending ~10 minutes before PET)
0.9% saline i.v. comparator
0.9% saline i.v. over 40 minutes (ending ~10 minutes before PET)
Esketamine bolus + infusion in crossover Pilot II (5 subjects).
0.10 mg/kg bolus over 5 min (start ~15 min before PET) plus 0.30 mg/kg infusion over 130 minutes (crossover)
R,S-ketamine bolus + infusion in crossover Pilot II (5 subjects).
0.20 mg/kg bolus over 5 min (start ~15 min before PET) plus 0.60 mg/kg infusion over 130 minutes (crossover)
R,S-ketamine single infusion Pilot I (12 subjects).
0.50 mg/kg i.v. over 40 minutes (ending ~10 minutes before PET)
R,S-ketamine single infusion Pilot III (12 subjects).
0.80 mg/kg i.v. over 50 minutes