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; - Sufficiënt 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. - Treatment Resistant Depression, 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; • The presence of current moderate or severe dependence of alcohol or drugs 6 months within screening according to the DSM-5, not including tobacco-related and caffeine-related disorders, ascertained by the MINI-plus interview at screening; • Current use of a MAOI in excess of a daily dose of 60 mg; • 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. In fertile women, a urine pregnancy test will be performed prior to Phase 1 (screening) and prior to Phase 2 (month 1) of the study. 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 absolute contra-indication for esketamine use (according to the Summaries of Product Characteristics) or ECT (according to Dutch ECT guidelines, Appendix A), namely pheochromocytoma, increased intracranial pressure, intracranial surgery ( 6 months ago), intracranial process, unstable cervical spine, carcinoid, severe COPD, severe obesity, pseudocholinesterase deficiency, malignant hyperthermia and congenital muscle diseases. Cardiovascular relative contra-indications will lead to consultation with a colleague from the cardiology department. Thi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1 The primary objective in phase 1 is to investigate whether oral esketamine treatment is non-inferior to ECT in terms of response rates. The main study parameter comprises the percentage of patients with a treatment response, defined as a >=30% reduction (i.e., MICD) on the MADRS, in the esketamine relative to the ECT condition after eight weeks of treatment. Phase 2 The primary objective in phase 2 is to compare the efficacy of maintenance treatment with either oral esketamine or ECT in preventing relapse (i.e., loss of response) in patients who responded to the acute treatment (phase 1). The main study parameter comprises the percentage of patients with a depression relapse (i.e., loss of response), defined as a | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives and respective study parameters include: 1. To investigate whether oral esketamine is non-inferior to ECT in patients with NTRD on the short-term in with regard to depression symptom severity, suicidality, clinical impression, functioning, and quality of life, measured by: a) Response rates, more strictly defined as a >=50% reduction on the MADRS. b) Change in self-rated depressive symptom severity, defined as a reduction in IDS-SR total score between baseline and 8-weeks of treatment. c) Change in suicidal ideation, defined as a reduction in Columbia Suicide Severity Rating Scale (C-SSRS) scores between baseline and 8-weeks of treatment. d) 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. e) Change in functioning, defined as a reduction in the WHO Disability Assessment Schedule (WHODAS) total score between baseline and 8-weeks of treatment. f) 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 on variables other than loss of response, as measured by: a) Remission rates, defined as MADRS total score 8 weeks of treatment and sustained during 1-year follow-up); b) Relapse in terms of loss of remission (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) Compar | — |
Countries
Netherlands
Outcome results
None listed