Treatment resistant major depressive disorder
Conditions
Interventions
Pharmaceutical Form: Capsule
INN or Proposed INN: Esketamine
CAS Number: 33795-24-3
Other descriptive name: ESKETAMINE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
University Medical Centre Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all the following criteria: - Male or female, age range: 18 to 80 years; - Signed informed consent; - Good understanding of spoken and written Dutch; - DSM-5 diagnosis of MDD, first or recurrent episode, ascertained by the Mini International Neuropsychiatry Interview (MINI-plus); - TRD, defined as nonresponse to at least 3 different classes of antidepressants during lifetime, all given in an adequate dose (i.e. defined daily dose) for at least 4 weeks; - At least moderately severe depression, defined by a score higher than 18 on HDRS17; - Current treatment with an officially approved antidepressant medicine. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 118 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation: - Bipolar depression or depression with psychotic features, according to the DSM-5; - Previous or comorbid schizophrenia spectrum or other psychotic disorder according to the DSM-5, not including MDD with psychotic features; - Comorbid severe personality disorder according to the DSM-5, that is the main reason for treatment; - Previous or comorbid moderate or severe dependence of alcohol or drugs according to the DSM-5, not including tobacco-related and caffeine-related disorders; - Recent (within the last 4 weeks) or current use of cannabis or any other non-prescribed psychoactive compounds, including Saint John’s wort; - Relevant neurological disorder, such as dementia or epilepsy; - Recent (within the last 4 weeks) change of antidepressant treatment; - ECT sessions or any other antidepressant treatment change planned for the period of the study; - Active suicidal intent, defined by scores higher than 2 on HDRS17 for suicidal ideation; - (Suspected) pregnancy, insufficient contraception or lactation. If there is any doubt, a pregnancy test is performed; - Recent (within the last 4 weeks) or current use of benzodiazepine and benzodiazepine-like agents (zolpidem, zopiclone) in excess of 2 mg lorazepam or an equivalent per day; - Recent (within the last 4 weeks) or current use of somatic medication that commonly affects mood, like oral corticosteroids; - Presence of any contra-indication for ketamine use, such as increased intracranial pressure, recent myocardial infarction or other relevant cardiac problems, severe hypertension, severe hyperthyroidism, severe liver problems, severe kidney problems, or the use of medication that ketamine interacts with on a major level, such as monoamine oxidase inhibitors; - Vision or hearing problems that cannot be corrected and that interfere with the ability to comply with treatments and/or assessments; - Mental incompetence to provide informed consent, based on the judgment of the general practitioner or treating psychiatrist of the participant; - Inability to comply with treatments and/or assessments, based on the judgment of the general practitioner or treating psychiatrist of the participant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The proposed study aims to examine the antidepressant efficacy of oral S-ketamine augmentation in patients with treatment resistant depression, treated with regular antidepressants in a double-blind randomised controlled trial. ;Secondary Objective: Secondary questions involve the effects of oral S-ketamine on sleep, autobiographical memory, pain, anxiety, anhedonia, suicidal ideation, nicotine dependence, quality of life and consumption of medical care, as well as a detailed assessment of possible side effects caused by the ketamine treatment. Brain activation, brain blood flow and volume parameters, neuroplasticity, glutamate and glutamine concentrations in the brain, biomarkers, and the genotype of the CYP enzyme(s) involved in the metabolism of ketamine will be assessed, to develop a better understanding of the mechanisms of action and metabolism of S-ketamine. Furthermore, the study will also investigate the duration of effects after discontinuation of S-ketamine add-on treatment.;Primary end point(s): The primary objective of this trial is to examine the antidepressant efficacy of oral S-ketamine augmentation in patients with TRD. This will be measured by the following main study endpoints at the end of treatment: 1) change in symptom severity, expressed as a change in total score on the HDRS17; 2) response, defined as = 50% decrease in total score on the HDRS17; 3) partial response, defined as 25-49% decrease in total score on the HDRS17.;Timepoint(s) of evaluation of this end point: At the end of treatment (week 6) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: There will be different timepoints for the secondary end points: - During treatment (week 0 - week 6); - At the end of treatment (week 6); - At follow-up (week 7, 8 and 10); ;Secondary end point(s): The secondary objectives of this trial will be measured by the following secondary study endpoints: - HDRS17 changes in total sum score after the discontinuation of treatment; - IDS-SR changes in total sum score during and after the discontinuation of treatment; - HDRS17 changes and IDS-SR changes in symptom dimension scores during and after the discontinuation of treatment; - BSS changes in total sum score during and after the discontinuation of treatment; - SHAPS changes in total sum score during and after the discontinuation of treatment; - fMRI reward task changes in total sum score during treatment; - CGI severity changes and CGI improvement scores during and after the discontinuation of treatment; - BAI changes in total sum score during and after the discontinuation of treatment; - GCPS changes in item scores during and after the discontinuation of treatment; - FTND changes in total sum score during and after the discontinuation of treatment; - AMT changes in total specific sum score during and after the discontinuation of treatment; - EQ-5D-5L changes in total sum score calculated using the Dutch tariff and in VAS score, during and after the discontinuation of treatment; - Changes of brain activation in the prefrontal cortex, limbic structures, insula and default mode network during treatment; - Changes of the prefrontal cortex and limbic structures volumes during treatment; - Changes of glutamate and glutamine concentrations in the anterior cingulate cortex of the brain during treatment; - Changes of blood flow in the brain during treatment; - Changes of biomarker patterns in blood and urine during and after the discontinuation of treatment; - Changes in gene expression patterns, measured by the use of RN | — |
Countries
Netherlands
Contacts
Public ContactUniversity Centre of Psychiatry
University Medical Centre Groningen
Outcome results
None listed