A randomised non-inferiority trial of esketamine versus electroconvulsive therapy in treatment-resistant depressio

Phase 3

• Conditions: sadness; Treatment-resistant depression; 10027946

• Registration Number: NL-OMON51415
• Lead Sponsor: niversitair Medisch Centrum Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 180

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

• 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To investigate whether oral esketamine is non-inferior to ECT, the short term<br /><br>effectiveness is measured by the percentage of patients with response to<br /><br>treatment at change from baseline in MADRS total score (defined as >=30%<br /><br>reduction or MCID) to 8 weeks of treatment, in patients with NTRD.</p><br>