Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboTerminated

Ketamine for Relapse Prevention in Recurrent Depressive Disorder

Randomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam for depression relapse prevention in persons at high risk. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.

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

Detailed Description

Participants admitted to St Patrick's University Hospital with DSM-IV recurrent unipolar depression receive treatment-as-usual and, if meeting response criteria, are randomised to four two-weekly infusions of ketamine (0.05 mg/kg) or midazolam (0.045 mg/kg) administered by an anaesthetist.

Outcomes include relapse over six months, physical, psychotomimetic and cognitive monitoring during infusions (observation ~200 minutes), and biomarker/epigenetic measures from blood sampled at multiple time points.

Design: randomised, double-blind, parallel-group pilot with block randomisation; anaesthetist administering infusions was unblinded while participants and raters were masked.

Study Protocol

Preparation

sessions

Dosing

4 sessions
200 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Four two-weekly intravenous infusions of ketamine (0.05 mg/kg) administered by a consultant anaesthetist.

Interventions

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

    Blood samples for biomarker/epigenetic studies; observation ~200 minutes post-infusion.

Midazolam

active comparator

Four two-weekly intravenous infusions of midazolam (0.045 mg/kg) administered by a consultant anaesthetist.

Interventions

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

    Midazolam (Hypnovel) 0.045 mg/kg; encoded as active comparator (compound set to placebo reference).

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • ≥18 years old
  • Hamilton Rating Scale for Depression, 24-item (HRSD-24) score of ≥21
  • Voluntary admission for treatment of acute depressive episode
  • Meet DSM-IV criteria for recurrent depressive disorder (RDD): ≥2 previous depressive episodes with at least 2-months(consecutive) subthreshold or no symptoms in between PLUS(to enrich the sample for those at high risk for relapse) must also have experienced ≥3 major depressive episodes(including index episode) within the previous 2 years
  • For the randomised pilot trial, RDD patients must have:
  • received antidepressant treatment for the acute depressive episode(pharmacological, psychotherapeutic or multidisciplinary)
  • ≥60% decrease from baseline HRSD-24 score and score ≤16
  • Standardised Mini-Mental State Examination (sMMSE) score of ≥24
  • able to provide informed consent

Exclusion Criteria

  • Exclusion Criteria:
  • Current involuntary admission
  • Medical condition rendering unfit for ketamine/midazolam
  • Active suicidal intention
  • Dementia
  • History of Axis 1 diagnosis other than RDD
  • Electroconvulsive therapy (ECT) for treatment of current depressive episode
  • Alcohol/substance abuse in previous six months
  • Pregnancy or inability to confirm use of adequate contraception during the trial

Study Details

Locations

St Patrick's University Hospital — Dublin, Ireland

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