sadness Treatment-resistant depression
Conditions
Interventions
Participants will be provided either oral esketamine or ECT twice a week. Both
conditions are individually tailored for optimal effectiveness. The esketamine
arm will start with an initial dose of 0
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • 18 years or older of age at screening; • Sufficient level of spoken and written Dutch; • Ability to freely provide written informed consent prior to study participation; • Current DSM-5 diagnosis of MDD without psychotic symptoms, ascertained by the Mini International Neuropsychiatry Interview (MINI-plus); • At least moderate to severe depression, defined by a MADRS total score >= 20; • Indication for ECT treatment for the treatment of the current depressive episode. • TRD, defined as non-response to (or established non-tolerability of) treatment with at least two different antidepressants plus an augmentation step such as lithium, mirtazapine or quetiapine during lifetime, all prescribed in an adequate dose (i.e. defined daily dose) for at least four weeks; • Patients agree with initial clinical admission and subsequent daycare/outpatient treatment.
Exclusion criteria
Exclusion criteria: • Prior or current bipolar disorder, schizophrenia spectrum, other psychotic disorders, current MDD with psychotic features (previous MDD with psychotic features is allowed if the current episode is non-psychotic). All diagnoses according to DSM-5, assessed with MINI-plus interview at screening; • Current use of a MAOI in excess of a daily dose of 60 mg; • The presence of current moderate or severe dependence of alcohol or drugs at screening according to the DSM-5, not including tobacco-related and caffeine-related disorders, ascertained by the MINI-plus; • Recent (within the last four weeks of screening) or current use of cannabis or any other non-prescribed psychoactive compounds, including Saint John*s wort, assessed at screening; • Relevant neurological disorders, such as dementia or epilepsy; • Recent (within the last four weeks of screening) change of treatment with antidepressants; • Planned changes in antidepressant treatment during phase 1 of the study, not being part of the standard practice of ECT treatment like change in lithium or anti-epileptics; • Active suicidal plans, defined by a score higher than 5 (explicit plans for suicide when there is an opportunity or active preparations for suicide) on the MADRS*s item for suicidal ideation; • (Suspected) pregnancy, lactation, or insufficient contraception. If there is any doubt, a pregnancy test is performed; • Current use of benzodiazepine and benzodiazepine-like agents (zolpidem, zopiclone) in excess of 3 mg lorazepam or an equivalent per day; • Recent (within the last four weeks of screening) start or change in the use of somatic medication that commonly affects mood, like corticosteroids; • Previous treatment with ECT or esketamine during the current depressive episode; • Presence of any contra-indication for esketamine use, such as increased intracranial pressure, cerebrovascular accident, cerebral trauma, glaucoma, recent myocardial infarction (<6 months), or other relevant cardiac problems like unstable angina pectoris or myocardial disease, aneurysmal vascular disease, severe hypertension, severe hyperthyroidism, severe liver problems, severe kidney problems, the use of medication that esketamine interacts with on a major level, such as monoamine oxidase inhibitors and xanthine derivates (aminophylline, theophylline) or previous hypersensitivity to esketamine or its components; While not exclusion criteria, enrolling a potential participant who meets any of the relative contra-indications for esketamine use according to the Summary of Product Characteristics (SPC), like clinically significant respiratory conditions, will be decided based on a per patient assessment of potential risk; • Presence of any contra-indication for ECT according to the Dutch Richtlijn Electroconvulsietherapie (2010) (appendix A). While not exclusion criteria, enrolling a potential participant who meets any of the relative contra-indications for ECT according to the Richtlijn Electroconvulsietherapie will be decided based on a perpatient assessment of potential risk; • Mental incompetence to fully understand the informed consent of this study, based on the judgment of the general practitioner or treating psychiatrist of the participant; • Inability to understand or comply with study requirements, as judged
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To investigate whether oral esketamine is non-inferior to ECT, the short term effectiveness is measured by the percentage of patients with response to treatment at change from baseline in MADRS total score (defined as >=30% reduction or MCID) to 8 weeks of treatment, in patients with NTRD. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives and endpoints include: 1. To investigate whether oral esketamine is non-inferior to ECT in patients with NTRD on the short term in depression symptom severity, suicidality, clinical impression, functioning, and quality of life, measured by: a) Change in depressive symptom severity, defined as a reduction in IDS-SR total score between baseline and 8-weeks of treatment. b) Change in suicidal ideation, defined as a reduction in Columbia Suicide Severity Rating Scale (C-SSRS) scores between baseline and 8-weeks of treatment. c) Change in general clinical impression, defined as a reduction in the Clinical Global Impression (CGI) score, the Clinical Global Impression Severity scale (CGI-S) score, and an increase in the Clinical Global Impression Improvement scale (CGI-I) score between baseline and 8-weeks of treatment. d) Change in functioning, defined as a reduction in the WHO Disability Assessment Schedule (WHODAS) total score between baseline and 8-weeks of treatment. e) Change in health-related quality of life, defined as a reduction in the 5-level Euroqol-5D (EQ-5D-5L) total score between baseline and 8-weeks of treatment. 2. To explore long-term effectiveness of oral esketamine treatment compared to ECT treatment in participants who respond to initial treatment, as measured by: a) Remission rates, defined as MADRS total score 8 weeks of treatment and sustained during 1-year follow-up); b) Relapse (within 6 months of remission) and recurrence (after 6 months of remission) rates, defined as: • Meeting the MADRS criteria for depressive disorder (total score >= 19) for at least two consecutive measurements, OR; • Worsening of symptoms requiring treatment policy change, OR; • Readmission to hospital, OR; • Suicide attempt. c) Comparing the differences in course of depression during the 52 weeks of follow-up between the two conditions, based upon the monthly MADRS and IDS-SR total scores. d) Change in depressive symptom | — |
Countries
Netherlands
Outcome results
None listed