Clinical TrialTreatment-Resistant Depression (TRD)EsketaminePlaceboNot yet recruiting

A randomised controlled trial of oral S-ketamine as add-on medication for patients with treatment-resistant major depressive disorder

Double-blind, randomised controlled add-on trial (n=128) testing oral S‑ketamine (vs placebo) TID for 6 weeks in patients with treatment-resistant major depressive disorder.

Target Enrollment
128 participants
Study Type
Phase NA interventional
Design
Randomized, double Blind
Registry
NTR / NL6030

Detailed Description

Randomised, double‑blind, parallel‑group add‑on trial comparing oral S‑ketamine versus matched placebo in 128 inpatients and outpatients with treatment‑resistant major depressive disorder (HDRS17 >18), continuing their existing antidepressant medication.

Treatment is administered three times daily for 6 weeks with tapered start and finish. Primary outcome is change in HDRS17 score and response rates; secondary assessments include multiple clinical scales, neuroimaging, pharmacokinetics, biomarkers and health‑economic outcomes.

Study Arms & Interventions

S-ketamine

experimental

Oral S-ketamine as add-on to ongoing antidepressant treatment for 6 weeks (tapered start and finish).

Interventions

  • Esketamine
    via Oral• three times daily

    Oral S‑ketamine TID for 6 weeks with tapered start and finish; exact mg not specified in registry.

Placebo

inactive

Matched oral placebo given as add-on for 6 weeks.

Interventions

  • Placebo
    via Oral• three times daily

    Matched placebo TID for 6 weeks.

Participants

Ages
18 – 80
Sexes
Male & Female

Inclusion Criteria

  • Male or female, age 18 to 80 years;
  • Signed informed consent;
  • Good understanding of spoken and written Dutch;
  • DSM-5 diagnosis of major depressive disorder (first or recurrent), confirmed by the MINI-plus;
  • Treatment-resistant depression (nonresponse to ≥3 different classes of antidepressants in lifetime, each given at adequate dose for ≥4 weeks);
  • At least moderately severe depression (HDRS17 score >18);
  • Current treatment with an approved antidepressant medication.

Exclusion Criteria

  • Bipolar depression or depression with psychotic features (DSM-5);
  • Previous or comorbid schizophrenia spectrum or other psychotic disorder;
  • Comorbid severe personality disorder that is the main reason for treatment;
  • Previous or comorbid moderate or severe dependence on alcohol or drugs (excluding tobacco and caffeine);
  • Recent (within 4 weeks) or current use of cannabis or other non-prescribed psychoactive compounds, including St John’s wort;
  • Relevant neurological disorder (e.g., dementia, epilepsy);
  • Recent (within 4 weeks) change of antidepressant treatment;
  • ECT sessions or any other planned antidepressant treatment change during the study;
  • Active suicidal intent (see suicidalityDetails);
  • Suspected pregnancy, insufficient contraception or lactation (pregnancy test if in doubt);
  • Recent/current use of benzodiazepines or Z-drugs in excess of 2 mg lorazepam equivalent per day;
  • Recent/current use of somatic medication that commonly affects mood (e.g., oral corticosteroids);
  • Any contraindication for ketamine use (e.g., increased intracranial pressure, recent myocardial infarction or relevant cardiac problems, severe hypertension, severe hyperthyroidism, severe liver or kidney problems, or use of major interacting medications such as MAOIs);
  • Uncorrected vision or hearing problems interfering with compliance;
  • Mental incompetence to provide informed consent;
  • Inability to comply with treatments and assessments.

Study Details

Locations

Netherlands

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