The Effect of a Four 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. (INTENSIFY MDD)
Major Depressive Disorder, Treatment Resistant Depression
About this trial
This is an interventional treatment trial for Major Depressive Disorder focused on measuring Major Depressive Disorder, Treatment as usual, Early treatment-resistance
Eligibility Criteria
Inclusion Criteria: In- or out patients, at least 18 years of age up until 70. Being willing and able to provide written informed consent. If unable, having a legal guardian to provide written informed consent is allowed (subject's opinion will also be considered in these cases). Female subjects of child bearing potential must use effective contraception during the trial and as per the requirements in the protocol (section 8.2). 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 experienced (in total) one treatment failure due to lack of efficacy; this treatment is a first-line pharmacotherapeutic agent for the primary DSM-5 diagnosis, and was prescribed for at least 4 weeks within the dose range as specified in the Summary of Product Characteristics (SmPCs). The psychopharmacological treatment failure (inclusion criterion 5) should be confirmed by a CGI-I ≥3. Subject and clinician intend to change pharmacotherapeutic treatment. 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 failed previously on (es)ketamine due to inefficacy (after treatment duration of ≥ 4 weeks within an efficacious dose range according to the SmPC. 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. 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 currently uses more than the allowed psychotropic concomitant medication and needs to stay on this medication during the study. 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. Moderate or high suicidal ideation within the last 2 weeks, defined as a score of 9 or higher on Module B (Suicidality) of the Mini International Neuropsychiatric Interview (MINI v7.0.2). 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 alcohol and/or cannabis use disorder (as defined by MINI v7.0.2). Moderate and severe alcohol and/or cannabis use disorder are not allowed. Subjects who are admitted in the (psychiatric) clinic due to a court or administrative order are not allowed to participate in the study.
Sites / Locations
- Medical University Innsbruck
- University Augsburg, BKH Augsburg, Department of Psychiatry, Psychotherapy and Psychosomatics
- Universitätsklinik für Psychiatrie und Psychotherapie Bielefeld
- University Hospital Frankfurt am Main - Goethe University
- Klinik für Psychiatrie und Psychotherapie der Universitätsmedizin Mainz
- Westfälische Wilhelms-Universität Münster
- Universita degli Studi di Brescia
- University of Cagliari
- Università degli studi della Campania Luigi Vanvitelli
- Azienda Ospedaliero-Universitaria "Città della Salute e della Scienza di Torino"
- Fundació Clínic per a la Recerca Biomèdica
- King's College London, Psychiatry & Cognitive Neuroscience
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Major Depressive Disorder EIPT: second-line antidepressant + esketamine nasal spray
Major Depressive Disorder TAU: second-line antidepressant
Major depressive disorder randomized to EIPT: Switch to second-line antidepressant + esketamine nasal spray or (es)ketamine infusion. Antidepressant: Compound, brand, dosage, frequency and duration up to the investigator's discretion (in accordance with SmPC). Esketamine nasal spray: 2 times per week for 4 weeks. Initial dose 28 mg, after that increases can be made with 28 mg per increase (up to 84 mg per week). This decision is up to the investigator's discretion (in accordance with SmPC). (Es)ketamine infusion: performed twice weekly for 4 weeks. Compound, brand up to the investigator's discretion (in accordance with SmPC).
Subject with major depressive disorder, randomized to TAU: switch to second-line antidepressant. When randomized to second-line anti-depressants, this means participants will receive treatment as usual. The physician has the choice to administer any second-line anti-depressant. More specification is not possible, as this is a choice the physician makes with the participant based on the characteristic and preference of the participant (in line with standard clinical practice).