Clinical TrialTreatment-Resistant Depression (TRD)EsketaminePlaceboActive not recruiting

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

This double-blind, placebo-controlled parallel-group Phase III trial (n=128) evaluates oral S-ketamine capsules as add-on treatment over 6 weeks for patients with treatment-resistant major depressive disorder (TRD).

Target Enrollment
128 participants
Study Type
Phase III interventional
Design
Randomized, double Blind

Detailed Description

Randomised, double-blind, placebo-controlled Phase III trial testing oral S-ketamine as an adjunct to standard antidepressants in patients with treatment-resistant major depressive disorder, with primary endpoint at week 6.

Secondary assessments include sleep, autobiographical memory, pain, anxiety, anhedonia, suicidal ideation, nicotine dependence, quality of life, health-care utilisation, pharmacokinetics of S-ketamine and norketamine, biomarkers, neuroimaging measures, and pharmacogenetic analyses.

The study is multicentre within the Netherlands (anticipated 4 sites), includes an independent data monitoring committee, and offers an open-label off-label ketamine extension after final follow-up for eligible participants.

Study Protocol

Preparation

sessions

Dosing

sessions

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

S-ketamine

experimental

Oral S-ketamine capsules as add-on to standard antidepressant treatment for 6 weeks.

Interventions

  • Esketamine
    via Oral• per protocol

    Oral S-ketamine capsules (strengths described 10 mg and 30 mg in protocol); dosing schedule given in protocol, treatment period 6 weeks.

Placebo

inactive

Matching oral placebo capsules as add-on to standard antidepressant treatment.

Interventions

  • Placebo
    via Oral• per protocol

    Matching capsule placebo.

Participants

Ages
18 – 80
Sexes
Male & Female

Inclusion Criteria

  • Male or female, age 18–80 years; signed informed consent; good understanding of spoken and written Dutch; DSM-5 diagnosis of major depressive disorder (first or recurrent) confirmed by MINI-plus; treatment-resistant depression defined as nonresponse to at least 3 different classes of antidepressants in lifetime (adequate dose ≥4 weeks); HDRS-17 score >18; current treatment with an approved antidepressant medication.

Exclusion Criteria

  • Bipolar depression or depression with psychotic features; current or past schizophrenia spectrum or other psychotic disorder (excluding MDD with psychotic features); comorbid severe personality disorder that is primary reason for treatment; 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 disorders (e.g., dementia, epilepsy); recent (within 4 weeks) change of antidepressant treatment; planned ECT or other antidepressant treatment changes during study; active suicidal intent (HDRS-17 suicidal ideation score >2); suspected pregnancy, insufficient contraception or lactation; recent (within 4 weeks) or current use of benzodiazepines/excessive hypnotics above lorazepam 2 mg/day equivalent; recent or current use of somatic medications that commonly affect mood (e.g., oral corticosteroids); contraindications to ketamine (increased intracranial pressure, recent MI or major cardiac problems, severe hypertension, severe hyperthyroidism, severe liver or kidney problems, interacting medications such as MAO inhibitors); uncorrected vision or hearing problems interfering with assessments; mental incompetence to consent; inability to comply with treatments or assessments.

Study Details

Locations

Netherlands

Your Library