Two-stage trial (n=60): open-label six IV ketamine infusions (0.5 mg/kg over 40 min) followed by double-blind randomised maintenance D-cycloserine versus placebo (titrated to 1000 mg/day) in ketamine responders to prevent relapse in TRD.
This study first administers six IV sub-anesthetic ketamine infusions (0.5 mg/kg over 40 minutes) over three weeks; responders (≥25% MADRS reduction) enter a randomised, triple-blind, placebo-controlled maintenance phase.
Responders are randomised to oral D-cycloserine or matched placebo, titrated 250→500→750→1000 mg/day and continued for eight weeks to evaluate relapse prevention; outcomes include MADRS, CGI, safety and vitals.
Responders to six IV ketamine infusions randomised to oral D-cycloserine maintenance (titrated to 1000 mg/day).
0.5 mg/kg over 40 minutes per infusion, six infusions over 3 weeks.
Titrated 250→500→750→1000 mg/day across weeks 4–11 (maintenance 8 weeks).
Responders to six IV ketamine infusions randomised to oral placebo maintenance (titrated matching DCS schedule).
0.5 mg/kg over 40 minutes per infusion, six infusions over 3 weeks.
Placebo pills titrated to match DCS schedule (250→1000 mg/day equivalent schedule).