Major depressive disorder Mental and Behavioural Disorders
Conditions
Interventions
Randomization
Participants are randomised using an online randomisation tool (www.sealedenvelope.com) to either placebo or ketamine arms. The randomisation code is drawn up by a researcher not involve
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female 2. Aged 20-60 years old 3. Willing and able to give informed consent for participation in the study 4. Sufficiently fluent English to understand and complete the tasks 5. Registered with a GP and consents to GP being informed of participation in the study 6. Participants need to meet a number of concurrent clinical criteria: Current criteria for Major Depressive Disorder, in a current major depressive episode, as determined by the SCID-5 7. Inadequate response to at least one and no more than three antidepressant treatments; Currently taking a licensed antidepressant at a therapeutic dose for at least four weeks 8. Pre-menopausal women and male participants engaging in sex with a risk of pregnancy must agree to use a highly effective method of contraception from Screening Visit until 30 days after receiving the study medication treatment 9. Male participants must not donate sperm until 30 days after receiving the study medication 10. Participants taking non-prescription/prescription medication may still be entered into the study, if, in the opinion of the Investigator, the medication received will not interfere with the study procedures or compromise safety 11. Willingness to refrain from driving, cycling, or operating heavy machinery, until the following morning or a restful sleep has occurred, whichever is later 12. Willingness to refrain from drinking alcohol for 3 days before the infusion visit and one day before any of the other visits throughout the study
Exclusion criteria
Exclusion criteria: 1. History of /or current DSM.5 bipolar disorder, schizophrenia or emotionally unstable personality disorder [co-morbid anxiety disorders (including agoraphobia, generalized anxiety disorder, social anxiety disorder and panic disorder) and Posttraumatic Stress Disorder (PTSD) are allowed] 2. Participants who fulfill current criteria for other comorbid disorders may still be entered into the study, if, in the opinion of the Investigator, the psychiatric diagnosis will not compromise safety or affect data quality 3. Diagnosis of a major cognitive disorder or evidence of cognitive impairment 4. Clinically significant risk of suicide 5. Participants undergoing or who have undergone electroconvulsive therapy for the treatment of the current episode of depression 6. Substance or alcohol use disorder over the past 6 months 7. Regular alcohol consumption of more than 21 units a week or excessive alcohol consumption up to three days before any of the in-person study visits or inability to abstain from alcohol for more than 3 days 8. Moderate cigarette use (> 10 cigarettes per day) 9. History of, or current general medical conditions that in the opinion of the Investigator may interfere with the safety of the participant or the scientific integrity of the study 10. Current pregnancy (as determined by urine pregnancy test), breastfeeding, planning a pregnancy, or unwillingness to practice birth control during the study 11. Clinically significant abnormalities of laboratory tests, physical examination, or ECG. A participant with a clinical abnormality or parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures 12. Current or history of heart rhythm disorders 13. Clinically significant untreated hypertension 14. Any contraindication to MRI including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more 15. Previous participation in a study using the same, or similar, emotional processing tasks in the last three months 16. Previous lifetime use of ketamine or phencyclidine 17. Participants with planned medical treatment within the study period that might interfere with the study procedures 18. Participant who is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Change in the magnitude of negative and positive valence adjectives in the autobiographical memory task measured using a self-reported questionnaire on day -1 and 1 day after ketamine/placebo treatment 2. Brain activation measured using functional magnetic resonance in a network of areas related to autobiographical memories, including the medial prefrontal cortex and associated networks during the autobiographical memory task 1 day after ketamine/placebo treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Accuracy measured using a computer-based task of facial expression recognition (FERT) on -1 day, and up to 2 hours after ketamine/placebo treatment 2. Reaction time measured using a computer-based task of facial expression recognition (FERT) on -1 day, and up to 2 hours after ketamine/placebo treatment 3. Accuracy to classify positive and negative descriptor words measured using the Emotional Categorisation Task (ECAT) up to 2 hours after ketamine/placebo treatment 4. Reaction time to classify positive and negative descriptor words measured using the Emotional Categorisation Task (ECAT) up to 2 hours after ketamine/placebo treatment 5. Number of positive and negative words correctly recalled (hits) and number of words incorrectly recalled (false alarms) measured using the Emotional Recall Task (EREC) up to 2 hours after ketamine/placebo treatment 6. Accuracy to correctly (hits) and incorrectly (false alarms) recognise positive and negative words measured using the Emotional Recognition Memory Task (EMEM) up to 2 hours after ketamine/placebo treatment 7. Reaction time to correctly (hits) and incorrectly (false alarms) recognise positive and negative words measured using the Emotional Recognition Memory Task (EMEM) up to 2 hours after ketamine/placebo treatment 8. Change in response choice during gain and loss measured using the Probabilistic Instrumental Learning Tasks (PILT) on 1 day after ketamine/placebo treatment 9. Brain activation measured using functional magnetic resonance imaging during the Probabilistic Instrumental Learning Tasks (PILT) in reward-related brain areas, including the ventral striatum and associated networks on 1 day after ketamine/placebo treatment 10. Explore performance on information processing and monetary win/loss reinforcement learning (RL) measured using decision-making tasks on 1 day after ketamine/placebo treatment 11. Explore performance on information processing and monetary win/loss reinforcement learning (RL) measured using de | — |
Countries
England, United Kingdom
Contacts
Public ContactChloe Wigg
Outcome results
None listed