Depression sadness
Conditions
Interventions
Subjects are randomly assigned to treatment with oral S-ketamine or placebo
during 6 weeks. The tapering-in process consists of gradually increase dosages
in the 4 first days of the treatment. The l
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Male or female, age range: 18 to 80 years; - Signed informed consent; - Good understanding of spoken and written Dutch; - DSM-5 diagnosis of Major Depresive Disorder, first or recurrent episode, ascertained by the Mini International Neuropsychiatry Interview (MINI-plus); - Treatment Resistant Depression, 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.
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.;For the MRI-scanning, there are additional exclusion criteria: - MRI incompatible implants in the body, such as cochlear implants, insulin pumps or other metal implants; - Any risk of having metal particles in the eye, for example due to manual work without proper eye protections; - Tattoos containing red pigments; - Claustrophobia; - The refusal to be informed of structural brain abnormalities that could be detected during the experiment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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: 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) To examine whether oral S-ketamine, compared to placebo, will: - Have sustained effect on reducing the severity of depression after the discontinuation of treatment, as measured with the HDRS17; - Reduce self-reported severity of depression, as measured with the IDS-SR; - Have a different effect in subgroups of patients, as measured with the HDRS17 and IDS-SR; - Reduce the severity of symptom dimensions, as measured with the HDRS17 and IDS-SR; - Reduce the severity of suicidal ideation, as measured with the Beck Scale for Suicide Ideation (BSS); - Reduce the severity of anhedonia, as measures with the Snaith-Hamilton Pleasure Scale (SHAPS) and the functional MRI (fMRI) Reward task; - Improve general clinical impression, as measured with the Clinical Global Impression (CGI); - Reduce anxiety symptoms, as measured with the BAI; - Reduce pain, as measured with the Graded Chronic Pain Scale (GCPS); - Reduce nicotine dependence, as measured with the Fagerström Test for Nicotine Dependence (FTND); - Improve auto-biographical memory, as measured with the Autobiographical Memory Test (AMT); - Improve health-related quality of life, as measured with the EuroQol-5D 5 Level (EQ-5D-5L); - Increase brain activation in the prefrontal cortex, investigated with fMRI scanning; - Reduce brain activation of limbic structures, insula, and the default mode network in responders, investigated with fMRI scanning; - Alter the volume of the prefrontal cortex and limbic structures, investigated with MRI scanning; - Alter glutamate and glutamine concentrations in the anterior cingulate cortex, investigated with Magnetic Resonance Spectroscopy (MRS) scanning; - Alter cerebral blood flow, investigated with Arterial Spin Labelling (ASL) scanning; - Change biomarkers patterns in blood and urine, pointing to changes in underlying disease mechanisms; - Change gene expression patterns in white blood cells, which could point at changes in neuroplasticity; - Indu | — |
Countries
Netherlands
Outcome results
None listed