The Effect of a Six Week Intensified Pharmacological Treatment for Major Depressive Disorder Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.
Recruiting · NCT05973851 · Interventional (participants receive a specific treatment)
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
Over 28 million people suffer from current depressive disorder in the European Union. Major depressive disorder (MDD) is one of the most common psychiatric illnesses. The symptoms cause clinically significant distress or impairment in social, occupational, and other important areas of functioning. To treat MDD, there are several antidepressants available and prescribing medication is a process of trial-and-error. Guidelines do not explicitly advise on the order in which antidepressant medication should be prescribed. The choice of antidepressant should be tailored to the patient, while involving the patient in the decision-making process. In general, the choice for the first- and second-line treatment will be a second-generation antidepressant. Recently, esketamine nasal spray (intranasal (IN) administration) was approved for patients with treatment-resistant MDD (TRD). A patient is diagnosed with TRD when having used two antidepressants in sufficient duration and adequate dose without sufficient effect. TRD is associated with a negative impact on quality of life, higher risk for hospitalisations and suicide, comorbidities, poorer social and occupational functioning and a high carer burden. The efficacy of intranasal use of esketamine has been demonstrated in MDD subjects with treatment-resistant symptoms but also in subjects with non-treatment resistant depression, and is approved by the FDA and EMA as a third-line treatment. Besides the registered esketamine nasal spray, which is not available in all countries to all patients because of the high costs, off-label utilization of (es)ketamine infusions (IV) is growing extensively over time to treat TRD. Research conducted so far indicates an unequivocal initial substantial response to (es)ketamine IV in MDD populations, regardless of whether or not patients suffer from treatment resistant MDD. However, until now, there has not been a study investigating this in a sufficiently large population. This may be a unique opportunity to potentially prevent patients progressing into a treatment resistant illness stage. The potential implications of the results of the current study are the prevention of unnecessary trials of ineffective treatments, reducing subject burden substantially, as well as a reduction of healthcare and societal costs.
Who can take part
Inclusion criteria
- In- or outpatients, at least 18 years of age up until 65.
- 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.
- 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).
- 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).
- 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).
- Subject and clinician intend to change pharmacotherapeutic treatment. However, other lines of treatment are allowed as well.
- 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
- Being pregnant or breastfeeding.
- Subject has used (es)ketamine previously for the treatment of depressive symptoms.
- Subject has a known intolerance to (es)ketamine or to all TAU medication.
- 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.
- 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.
- 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.
- 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
- 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.
- Subjects have not been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
- Subjects dependent on the sponsor, investigator or trial site must be excluded from participation in advance.
Where it is running
12 locations listed.
- Eginition Hospital, department of psychiatry - Athens, Greece
- Fundació Clínic per a la Recerca Biomèdica - Barcelona, Spain
- Universitätsklinik für Psychiatrie und Psychotherapie Bielefeld - Bielefeld, Germany
- Universita degli Studi di Brescia - Brescia, Italy
- University of Cagliari - Cagliari, Italy
- LWL-Klinik Dortmund, Bereich Forschung & Wissenschaft - Dortmund, Germany
- University Hospital Frankfurt am Main - Goethe University - Frankfurt am Main, Germany
- Medical University Innsbruck - Innsbruck, Austria
- King's College London, Psychiatry & Cognitive Neuroscience - London, United Kingdom
- Westfälische Wilhelms-Universität Münster - Münster, Germany
- Università degli studi della Campania Luigi Vanvitelli - Naples, Italy
- Azienda Ospedaliero-Universitaria "Città della Salute e della Scienza di Torino" - Turin, Italy