Intensified treatment for major depressive disorder after first treatment failure

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial investigates the effects of a six-week intensified pharmacological treatment for patients with major depressive disorder (MDD) who have experienced a first treatment failure. The study compares this intensified approach using esketamine nasal spray and other antidepressants to the standard treatment as usual. Participants will be closely monitored to assess the efficacy of the new treatment regimen in improving depressive symptoms. The trial aims to provide a more effective treatment option for individuals struggling with treatment-resistant depression.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. In- or outpatients, at least 18 years of age up until 65.
2. Being willing and able to provide written informed consent. Having a legal guardian to cosign is allowed. Informed consent will be signed at visit 1, before any study procedure.
3. Female subjects of child bearing potential must use effective contraception during the trial as per the requirements of the applicable SmPCs and should have a negative pregnancy test at visit 1 or 2 (before randomisation).
4. Meeting diagnostic criteria for a primary diagnosis of major depressive disorder (without psychotic features), according to DSM-5. The primary diagnosis will be confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2).
5. Subject experiences a treatment failure due to lack of efficacy in the current episode, as confirmed by a CGI-I ≥3; perferably, this treatment is a first-line pharmacotherapeutic agent for the primary DSM-5 diagnosis, and was prescribed for at least 4 weeks within an effective dose range as specified in the Summary of Product Characteristics (SmPCs).
6. Subject and clinician intend to change pharmacotherapeutic treatment. However, other lines of treatment are allowed as well.
7. A minimum symptom severity threshold needs to be present (moderate level; see below) and subject needs to experience functional impairment.

   * The minimum symptom severity threshold is a score of ≥20 on the Montgomery Åsberg Depression Rating Scale (MADRS)
   * Functional impairment is defined as a score of 5 or higher on any of the three scales of the Sheehan Disability Scale (SDS).

Exclusion criteria:

1. Being pregnant or breastfeeding.
2. Subject has used (es)ketamine previously for the treatment of depressive symptoms.
3. Subject has a known intolerance to (es)ketamine or to all TAU medication.
4. Meeting any of the contraindications for (es)ketamine, or to all TAU medication options, as specified within the applicable SmPC, supported by clinically significant abnormal values on local laboratory tests, electrocardiogram (ECG) or physical examinations.
5. Subject has participated in another clinical trial in which the subject received an experimental or investigational drug or agent within 30 days before visit 1.
6. Subject experiences any other significant disease or disorder which, in the opinion of the investigator, may either put the subjects at risk because of participation in the trial, or may influence the result of the trial, or the subject's ability to participate in the trial.
7. Subjects with active suicidal ideation with some intent to act, without specific plan ("Yes" to question 4 of the Columbia-Suicide Severity Rating Scale (C-SSRS)) or active suicidal ideation with specific plan and intent ("Yes" to question 5 of the C-SSRS), followed by an assessment by the treating clinician who determines it is not safe for the subject to participate in the study
8. Subject meets criteria for current substance use disorder, as confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2). Nicotine dependency is allowed, as well as mild and moderate alcohol and/or cannabis use disorder (as defined by MINI v7.0.2). Severe alcohol and/or cannabis use disorder are not allowed.
9. Subjects have not been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
10. Subjects dependent on the sponsor, investigator or trial site must be excluded from participation in advance.

Where it's running

• Medical University Innsbruck
  Innsbruck, Austria Recruiting
• Universitätsklinik für Psychiatrie und Psychotherapie Bielefeld
  Bielefeld, Germany Recruiting
• LWL-Klinik Dortmund, Bereich Forschung & Wissenschaft
  Dortmund, Germany Recruiting
• University Hospital Frankfurt am Main - Goethe University
  Frankfurt am Main, Germany Recruiting
• Westfälische Wilhelms-Universität Münster
  Münster, Germany Recruiting
• University of Cagliari
  Cagliari, Italy Recruiting

Study contacts

• Study coordinator: Inge Winter, Dr.
• Email: i.winter@umcutrecht.nl
• Phone: +31875553227

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Mindfulness‑augmented brain stimulation for treatment‑resistant depression

  This trial will test whether combining fast brain stimulation (iTBS) with a digital mindfulness program helps people with treatment‑resistant depression reduce symptoms and improve thinking.

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• Adding ketamine to ECT for treatment-resistant depression

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  Recruiting Phase 3 Università Vita-Salute San Raffaele · Milan · NCT07088380

• Maintenance treatment using rTMS for depression

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  Recruiting at 3 sites University of California, San Diego · San Diego, California and 2 other locations · NCT06938841

• Identifying brain biomarkers for treatment-resistant major depression using deep brain stimulation

  This study is testing if deep brain stimulation can help people with severe depression who haven't found relief from regular treatments by looking for brain signals that could predict their mood changes.

  Recruiting West China Hospital · Chengdu, Sichuan · NCT06542094

• Using gamma oscillations to predict ketamine therapy outcomes in depression

  This study is testing if brain activity measured during ketamine treatment can help predict how well it will work for people with depression that hasn't responded to other treatments.

  Recruiting at 2 sites Phase 1 Texas A&M University · Houston, Texas and 1 other locations · NCT06480201

• Understanding the impact of mood disorders and treatment responses

  This study is trying to learn more about how people with depression and bipolar disorder respond to treatment by talking to them weekly for up to 12 weeks to improve future care and predict how well medications might work.

  Recruiting National Institutes of Health Clinical Center (CC) · Bethesda, Maryland · NCT06462196

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.