Clinical TrialCrossoverTreatment-Resistant Depression (TRD)KetaminePlaceboCompleted

A randomised, double blind, active placebo-controlled crossover trial to evaluate the short term efficacy of an N-Methyl-D-Aspartate antagonist for patients with treatment resistant depression

This randomised, double-blind, active placebo-controlled crossover trial (n=30) investigates the short-term efficacy of ketamine for patients with treatment-resistant depression (TRD).

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Target Enrollment
30 participants
Study Type
Phase II/III interventional
Design
Randomized, double Blind

Detailed Description

Randomised, double-blind crossover comparing single IV ketamine (bolus 0.25 mg/kg then infusion 0.25 mg/kg/hr for 45 minutes) with an active remifentanil comparator; 3-week washout between sessions.

Primary outcome assessed with MADRS; ancillary measures include plasma BDNF at 4 hours post-intervention and follow-ups at days 1, 7, 14 and 21 during a 42-day study period.

Study Protocol

Preparation

sessions

Dosing

2 sessions
45 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Single IV ketamine session (bolus + short infusion) as active treatment in crossover.

Interventions

  • Ketamine0.25 mg/kg
    via IV• single dose• 1 doses total

    IV bolus 0.25 mg/kg then infusion 0.25 mg/kg/hr for 45 minutes.

Remifentanil

active comparator

Active placebo comparator using remifentanil target-controlled infusion.

Interventions

  • Placebo1.7 ng/mL
    via IV• single dose• 1 doses total

    Target-controlled remifentanil infusion to a 1.7 ng/mL plasma concentration over 9 minutes; active placebo in crossover.

Participants

Ages
18 – 60
Sexes
Male & Female

Inclusion Criteria

  • Participant is willing and able to give informed consent for participation in the trial.
  • Male or female, aged 18 years or above and less than 60.
  • In the Investigators’ opinion, is able and willing to comply with all trial requirements.
  • Major depressive disorder for at least three months, as assessed by a Clinical Interview using DSM-IV criteria.
  • MADRS >20.
  • An inadequate response to at least two antidepressant courses (Antidepressant Treatment History Form) one of which can include the current episode.
  • Stable on antidepressant medication for four weeks prior to Study Day 1.

Exclusion Criteria

  • Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
  • Significant renal or hepatic impairment.
  • Cardiovascular conditions including abnormal heart rate and blood pressure checked at screening.
  • Participants who have participated in another research trial involving an investigational product in the past 12 weeks.
  • History of psychosis.
  • Any unstable medical or neurologic condition.
  • Planned major changes to psychotropic medication.
  • Imminent risk of suicide as determined by the CSSRS.
  • Planned or probable use of ECT.
  • Substance abuse or dependence in previous 6 months.
  • Any history of abuse of ketamine or phencyclidine.
  • Contraindication to the use of ketamine according to manufacturer guidelines.
  • Planned use of ketamine, for example, for pain control.
  • Unable to fast for four hours prior to each administration of trial drug.
  • Any other condition judged by the treating clinician as likely to impact on the ability of the participant to complete the trial.
  • Body-weight <50kg or >120kg.
  • Current use of NMDA antagonist medications (e.g. memantine / amantadine / rimantadine / lamotrigine / dextromethorphan/procyclidine).
  • Inability to speak or read English.
  • Contraindications for MRI scanning.

Study Protocol, Arms & Participants

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Study Details

Locations

Unknown facility — Australia

Related Publications

PaywallindividualPrimary

Ketamine improves short-term plasticity in depression by enhancing sensitivity to prediction errors

This EEG study (n=30) in patients with depression shows that prediction error sensitivity (a possible proxy for brain plasticity, lacking in this population) is improved by ketamine (30.8mg/70kg).

Published
Journal
European Neuropsychopharmacology
Authors
Sumner, R. L., Mcmillan, R., Spriggs, M. J., Campbell, D., Malpas, G., Maxwell, E., Deng, C., Hay, J., Ponton, R., Sundram, F., Muthukumaraswamy, S. D.
PaywallindividualSecondary analysis

A qualitative and quantitative account of patient’s experiences of ketamine and its antidepressant properties

In 32 people with major depressive disorder given subanaesthetic ketamine versus an active placebo, larger 24‑hour antidepressant responses correlated with psychedelic dimensions (spirituality, unity, insight) and qualitative interviews documented pervasive perceptual changes, loss of control, emotional shifts and a lasting afterglow that altered perspectives on life and treatment. These findings give preliminary evidence that the acute psychedelic experience and afterglow contribute to ketamine’s antidepressant effects and that common questionnaires may not fully capture its phenomenology.

Published
Journal
Journal of Psychopharmacology
Authors
Sumner, R. L., Chacko, E., Mcmillan, R., Spriggs, M. J., Anderson, C., Chen, J., French, A., Jung, S., Rajan, A., Malpas, G., Hay, J., Ponton, R., Muthukumaraswamy, S. D., Sundram, F.

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