Clinical TrialDepressive DisordersKetaminePlaceboCompleted

Ketamine as an Adjunctive Therapy for Major Depression (2) (KARMA-Dep2)

This parallel-group, randomised, quadruple-blind, controlled trial (n=104 planned; 63 actual) compares up to eight IV ketamine infusions (0.05 mg/kg) versus midazolam (0.045 mg/kg) in inpatients with major depressive episodes.

Target Enrollment
63 participants
Study Type
Phase III interventional
Design
Randomized, quadruple Blind

Detailed Description

Pragmatic, randomised, parallel-group superiority trial in patients admitted to St Patrick's University Hospital for a major depressive episode; participants randomised 1:1 to up to eight twice-weekly infusions of ketamine or midazolam over up to four weeks.

Primary outcome compares mood-rating change from before first infusion to 24 hours after final infusion; participants followed for 24 weeks to assess relapse. Blinding includes participants and assessors; clinical and safety monitoring performed throughout.

Study Protocol

Preparation

sessions

Dosing

8 sessions

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Up to eight twice-weekly sub-anaesthetic ketamine infusions over up to four weeks (inpatient), administered by anaesthetist.

Interventions

  • Ketamine0.05 mg/kg
    via IV• twice weekly• 8 doses total

    Up to eight infusions over four weeks; administered by consultant anaesthetist.

Midazolam

active comparator

Up to eight twice-weekly midazolam infusions over up to four weeks (inpatient), administered by anaesthetist.

Interventions

  • Placebo0.045 mg/kg
    via IV• twice weekly• 8 doses total

    Midazolam (Hypnovel) 0.045 mg/kg given as active comparator; recorded as active comparator in registry.

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • ≥18 years old.
  • Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 20 at screening and start of the first infusion.
  • Voluntary admission for treatment of an acute depressive episode.
  • Meet DSM-5 criteria for a major depressive disorder or bipolar affective disorder (current episode depression). Diagnosis confirmed by the MINI (Version 7 for DSM-5).

Exclusion Criteria

  • Exclusion Criteria:
  • Current involuntary admission.
  • Medical condition rendering unfit for ketamine/midazolam.
  • Currently taking contraindicated medications that may alter the pharmacokinetics of ketamine.
  • Active suicidal intention.
  • Dementia.
  • Lifetime history of schizophrenia or schizoaffective disorder; active anorexia nervosa or bulimia nervosa in the past 12 months; alcohol or other substance use disorder (except nicotine) in the previous six months; any DSM-5 disorder other than a major depressive episode (unipolar or bipolar) as the primary presenting problem.
  • Electroconvulsive Therapy (ECT) administered within the last two months.
  • Pregnancy, breastfeeding or considering becoming pregnant whilst on the trial for up to 12 weeks after last dose or inability to confirm use of adequate contraception during the trial.
  • Breastfeeding women.

Study Details

  • Status
    Completed
  • Phase
    Phase III
  • Type
    interventional
  • Design
    Randomizedquadruple Blind
  • Target Enrollment63 participants
  • Timeline
    Start: 2021-09-13
    End: 2024-12-01
  • Compounds
    KetaminePlacebo
  • Topic
    Depressive Disorders

Locations

St Patrick's Univeristy Hospital — Dublin, Ireland

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