Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboCompleted

Ketamine for Depression Relapse Prevention Following ECT

Randomised, triple-blind, parallel pilot trial (n=6) comparing once-weekly IV ketamine 0.5 mg/kg vs midazolam 0.045 mg/kg for up to four weeks to prevent relapse after successful ECT in adults with major depressive disorder.

Target Enrollment
6 participants
Study Type
Phase I interventional
Design
Randomized, triple Blind

Detailed Description

This pilot trial recruited ECT responders with major depressive disorder and randomised consenting responders to once-weekly intravenous ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) infusions for up to four weeks, with six-month follow-up for relapse.

The primary aim was feasibility and process outcomes to inform a definitive trial; the clinical secondary outcome was relapse rate at six months measured by the HRSD-24. Safety, cognitive effects and dissociative/psychotomimetic symptoms were assessed during and after infusions.

Assessments included baseline and weekly HRSD-24 scores, CADSS and BPRS for dissociative and psychotomimetic effects, cognitive battery including ACE-R and K-AMI, and monitoring of adverse events throughout the study.

Study Protocol

Preparation

sessions

Dosing

4 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Intravenous ketamine infusions 0.5 mg/kg over 40 minutes, up to four once-weekly infusions.

Interventions

  • Ketamine0.5 mg/kg
    via IV• weekly• 4 doses total

    Infusion over 40 minutes; course up to four once-weekly infusions.

Midazolam

active comparator

Intravenous midazolam 0.045 mg/kg over 40 minutes, up to four once-weekly infusions (active comparator).

Interventions

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

    Midazolam 0.045 mg/kg (Roche Products Ireland Ltd) as active comparator; prepared as 50 ml saline infusion over 40 minutes.

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Patients ≥18 years with unipolar major depressive disorder (DSM-IV)
  • 24-item Hamilton Rating Scale for Depression (HRSD-24) score of ≥21
  • Referred for ECT
  • For the randomised Phase 2, patients must have
  • received a substantial course of ECT in Phase 1 (i.e. at least five sessions)
  • achieved at least response criteria (i.e. ≥60% decrease from baseline HRSD-24 score and score ≤16 on two consecutive weekly ratings)
  • have a nominated adult who can stay with them for 24-hours on out-patient treatment days
  • Mini-Mental State Examination (MMSE) score of ≥24
  • able to provide informed consent

Exclusion Criteria

  • Exclusion Criteria:
  • Any condition rendering patient medically unfit for ECT; general anaesthesia, ketamine or midazolam - assessed by physical examination, routine haematology and biochemistry investigations prior to enrolment in Phase I (routine care)
  • Active suicidal intention
  • Dementia, intellectual disability, or MMSE <24
  • Lifetime history of bipolar affective disorder
  • Current history of post-traumatic stress disorder
  • Other Axis I diagnosis (DSM-IV)
  • ECT in the six months prior to recruitment
  • Alcohol dependence or substance misuse in the six months prior to recruitment
  • Pregnancy or breast-feeding
  • Residing in a nursing home
  • Prisoner
  • Diagnosis of terminal illness
  • Inability or refusal to provide valid informed consent

Study Details

Locations

St Patrick's University Hospital — Dublin, Ireland

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