Skip to content
Clinical Trials – home

Rare diseases

Investigational molecules

Locations

Our offerNewsroom

Not yet recruitingRare disease

Title: Comparison of Oral Esketamine versus Electroconvulsive Therapy in Patients with Treatment-Resistant Depression

Fast replyRegistered drugNo placebo
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

What is this trial about?

A plain-language summary of the goals, design and what participants do

This study focuses on patients with non-psychotic therapy resistant unipolar depression, a severe form of depression that has not improved with standard treatments. The research compares two different treatments: oral esketamine (a medication) and Electroconvulsive Therapy (ECT). The purpose is to determine if oral esketamine works as effectively as ECT in treating this type of depression.

The study is divided into two phases. In the first phase, lasting eight weeks, patients receive either oral esketamine or ECT treatment. The second phase extends for one year and examines how well these treatments prevent the depression from returning in patients who showed improvement during the first phase.

During the treatment period, patients initially receive care in a hospital setting and then continue their treatment as outpatients. The medication being tested, esketamine, is a modified version of an existing injectable solution that has been adapted for oral use by adding ingredients to make it suitable for taking by mouth. The maximum daily dose of esketamine is 3.0 mg per kilogram of body weight, and treatment can continue for up to 60 days.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial assessment

    A medical evaluation will confirm if you have non-psychotic therapy resistant depression

    Your depression severity will be measured using a special assessment tool called MADRS to ensure your score is 20 or higher

    The evaluation will verify that you have previously tried at least two different antidepressants plus additional medication without success

  2. Step 2

    Treatment phase 1 - First 8 weeks

    You will be randomly assigned to receive either oral esketamine or ECT (Electroconvulsive Therapy)

    The treatment will be adjusted to your individual needs during this 8-week period

    Your depression symptoms will be monitored to measure if there is at least 30% improvement in your condition

  3. Step 3

    Response evaluation

    After 8 weeks, your response to the treatment will be evaluated

    A successful response is defined as at least 30% reduction in depression symptoms

    This evaluation will determine if you continue to phase 2 of the study

  4. Step 4

    Treatment phase 2 - Maintenance period

    If you responded well to the initial treatment, you will continue with the same treatment approach

    This maintenance phase will last for 12 months

    Regular evaluations will monitor if your improvement is maintained

    The goal is to prevent the return of depression symptoms

  5. Step 5

    Final assessment

    After the 12-month maintenance period, a final evaluation will be conducted

    The assessment will determine the long-term effectiveness of your treatment

    The study will conclude in November 2026

Who can join the trial?

10 criteria

  • Age 18 years or older at the time of screening
  • Must be able to understand and communicate in both written and spoken Dutch
  • Must be able to provide written informed consent (formal agreement to participate) voluntarily
  • Current diagnosis of Major Depressive Disorder (MDD) without psychotic symptoms, confirmed through a specialized psychiatric interview
  • Depression must be moderate to severe, as measured by a specific depression rating scale score of 20 or higher
  • Must have a medical indication for ECT treatment (Electroconvulsive Therapy) for current depression
  • Must have treatment-resistant depression, meaning:
    • Previous unsuccessful treatment with at least two different antidepressants
    • Failed additional treatment with medications such as lithium, mirtazapine, or quetiapine
    • Each medication must have been taken at adequate doses for at least 4 weeks
    • Must agree to initial hospital admission followed by day treatment or outpatient care

Who cannot join the trial?

13 criteria

  • Current or past diagnosis of bipolar disorder (a mental health condition causing extreme mood swings)
  • Presence of psychotic symptoms (loss of touch with reality, such as hallucinations or delusions)
  • History of substance abuse within the past 6 months
  • Severe medical conditions that could interfere with treatment safety
  • Pregnant or breastfeeding women
  • Previous unsuccessful treatment with ECT (Electroconvulsive Therapy) or esketamine
  • Known allergy or hypersensitivity to ketamine or esketamine
  • Severe liver or kidney disease
  • Uncontrolled high blood pressure
  • History of bleeding in the brain
  • Current use of certain medications that might interact with study treatments
  • Inability to provide informed consent
  • Participation in another clinical trial within the past 30 days
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Not yet recruiting
Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

Investigated drugs

  • Esketamine

    (oral form) is a medication used to treat severe depression that hasn't responded to other treatments. It works by targeting brain receptors involved in mood regulation. This medication is a modified form of ketamine and is taken by mouth to help improve depressive symptoms in people who haven't found relief with standard antidepressants.

  • Electroconvulsive Therapy (ECT)

    is a medical procedure that involves passing small electrical currents through the brain while the patient is under anesthesia. This treatment causes brief changes in brain chemistry that can quickly reverse symptoms of certain mental health conditions, particularly severe depression. It's typically used when other treatments haven't been successful.

What is already known about the treatment

Esketamine - An advanced antidepressant medication administered orally that represents the S-enantiomer of ketamine, specifically designed for treatment-resistant unipolar depression. This medication works by acting as an NMDA receptor antagonist in the brain, helping to restore neural connections and reduce depressive symptoms in patients who haven't responded to conventional antidepressant treatments. Currently undergoing clinical trials as a potential alternative to electroconvulsive therapy (ECT), esketamine belongs to the class of glutamate modulators and represents a novel approach in treating severe depression, with studies focusing on both its acute therapeutic effects and long-term maintenance potential in preventing depressive relapses.

Investigated diseases

Non-psychotic Therapy Resistant Unipolar Depression - A severe form of major depressive disorder that has not responded to at least two different antidepressant treatments. It is characterized by persistent low mood, loss of interest in activities, changes in sleep and appetite, and reduced energy levels that continue despite standard treatments. The condition affects daily functioning and occurs without psychotic symptoms such as hallucinations or delusions. This form of depression shows minimal or no improvement with conventional antidepressant medications over extended periods.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2024-517485-42-00Estimated enrolment172 patientsSponsorUniversitair Medisch Centrum Groningen

sourced from the EU Clinical Trials Register and site verification

Want to learn more about this trial or check if you can participate?

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.