Clinical TrialTreatment-Resistant Depression (TRD)KetamineKetaminePlaceboUnknown status

D-cycloserine for Relapse Prevention Following Intravenous Ketamine in Treatment-resistant Depression

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.

Target Enrollment
60 participants
Study Type
Phase IV interventional
Design
Randomized, triple Blind

Detailed Description

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.

Study Protocol

Preparation

sessions

Dosing

6 sessions
40 min each

Integration

sessions

Study Arms & Interventions

DCS

experimental

Responders to six IV ketamine infusions randomised to oral D-cycloserine maintenance (titrated to 1000 mg/day).

Interventions

  • Ketamine0.5 mg/kg
    via IV• six infusions• 6 doses total

    0.5 mg/kg over 40 minutes per infusion, six infusions over 3 weeks.

  • Compound1000 - 1000 mg
    via Oral• daily• 56 doses total

    Titrated 250→500→750→1000 mg/day across weeks 4–11 (maintenance 8 weeks).

Placebo

inactive

Responders to six IV ketamine infusions randomised to oral placebo maintenance (titrated matching DCS schedule).

Interventions

  • Ketamine0.5 mg/kg
    via IV• six infusions• 6 doses total

    0.5 mg/kg over 40 minutes per infusion, six infusions over 3 weeks.

  • Placebo
    via Oral• daily• 56 doses total

    Placebo pills titrated to match DCS schedule (250→1000 mg/day equivalent schedule).

Participants

Ages
18 – 74
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Patients aged 18-75 meeting DSM-V criteria for moderate-severe depression (MADRS≥25), who did not respond to two adequate antidepressant courses of treatment. Subjects will be required to continue on a stable dose of any psychotropic medication they are taking, for 8 weeks prior to ketamine infusion. Participants who respond to ketamine (reduction of 25% in symptoms) would be invited to participate in a second stage of the experiment, in which participants would consume DCS for 8 weeks (weeks 4-11).

Exclusion Criteria

  • Exclusion Criteria:
  • Patients will be excluded if they have current or history of psychotic or dissociative symptoms, or severe personality disorder with psychosis or dissociative symptoms. Additional exclusion criteria will be a lifetime history of psychotic mania, a substance abuse or use of alcohol. Medical exclusion criteria will include - uncontrolled elevated blood pressure, non-sinus rhythm, unstable ischemic heart disease, uncorrected hyper thyroidism, and for women, pregnancy or the initiation of female hormonal treatment <3 months. Before ketamine treatment women of childbearing age will be required to use a medical accepted contraceptive or abstain from sexual activity. In addition patients will be excluded if they suffer from chronic renal failure, epilepsy, organic brain disorder or neurological or an unstable medical condition. Due to neurotoxicity and convulsions, patients will be prohibited to consume alcohol.

Study Details

Locations

Psychiatry Clinic - Sheba Medical Center — Ramat Gan, Israel

Your Library