Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboCompleted

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

Randomised, quadruple-blind, parallel-group pilot trial (n=25) of four once-weekly IV ketamine infusions (0.05 mg/kg) versus midazolam infusions (0.045 mg/kg) as adjunctive treatment for inpatients with acute depressive episodes to assess trial processes and preliminary outcomes.

Target Enrollment
25 participants
Study Type
Phase I interventional
Design
Randomized, quadruple Blind

Detailed Description

Pragmatic, randomised, controlled, parallel-group pilot trial enrolling inpatients admitted to St Patrick's University Hospital for an acute depressive episode; participants were randomised 1:1 to ketamine or midazolam.

Intervention comprised four once-weekly sub-anaesthetic IV infusions (ketamine 0.05 mg/kg or midazolam 0.045 mg/kg) administered by a consultant anaesthetist; both participants and assessors were blinded.

Outcomes included physical, psychotomimetic and cognitive measures collected before, during and after infusions; blood samples were taken at four time-points during the first infusion and before the final infusion for neuroplasticity biomarker studies, with follow-up over three months.

Study Protocol

Preparation

sessions

Dosing

4 sessions

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Four once-weekly sub-anaesthetic ketamine infusions administered by a consultant anaesthetist.

Interventions

  • Ketamine0.05 mg/kg
    via IV• weekly• 4 doses total

    Four once-weekly infusions; blood sampling at four time-points during first infusion and before final infusion for biomarker studies.

Midazolam

active comparator

Four once-weekly sub-anaesthetic midazolam infusions administered by a consultant anaesthetist.

Interventions

  • Placebo0.045 mg/kg
    via IV• weekly• 4 doses total

    Midazolam 0.045 mg/kg (active comparator; recorded as compoundReport.placebo with name in notes).

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • ≥18 years old
  • Hamilton Rating Scale for Depression-24 item version (HRSD-24) score of ≥21
  • Voluntary admission for treatment of an acute depressive episode
  • Meet DSM‑V criteria for a major depressive disorder (MDD) or bipolar affective disorder (current episode depression)

Exclusion Criteria

  • Exclusion Criteria:
  • Current involuntary admission
  • Medical condition rendering unfit for ketamine/midazolam
  • Active suicidal intention
  • Dementia
  • History of Axis I diagnosis other than major depression
  • Electroconvulsive Therapy (ECT) administered within the last two months
  • Alcohol/substance dependence in previous six months
  • Pregnancy or inability to confirm use of adequate contraception during the trial
  • Breastfeeding women

Study Details

Locations

St Patrick's University Hospital — Dublin, Ireland

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