Table 1 Inclusion and exclusion criteria
Inclusion criteria | 1. Adult (aged ≥ 18 years) male or female voluntary admission able and willing to give written informed consent and comply with the requirements of this study protocol |
2. Admitted to hospital and diagnosed with major depressive disorder or bipolar disorder (current episode depression), confirmed by the MINI and have a MADRS score ≥ 20 at screening and start of the first infusion | |
3. Female patients of child-bearing potential and male patients whose partner is of child-bearing potential must be willing to ensure that they or their partner use two contraception methods, including a barrier method, during the randomised treatment phase and for 12 weeks thereafter | |
4. Female patients’ plasma pregnancy test performed at the screening visit must be negative | |
5. Patients have clinically acceptable laboratory and ECG findings during the current admission prior to the first infusion session | |
Exclusion criteria | 1. Current involuntary admission |
2. Patients unable to provide written informed consent | |
3. Patients who have participated in another ketamine study or received any other investigational agent within the past 12 months | |
4. Medical condition rendering unfit for ketamine or midazolam (Ketamine is contraindicated, as per Summary of Product Characteristics, in persons in whom an elevation of blood pressure would constitute a serious hazard. Ketamine should not be used in patients with eclampsia or pre-eclampsia, severe coronary or myocardial disease, CVA or cerebral trauma or if there is hypersensitivity to the active substance. Contraindications to midazolam include known hypersensitivity to benzodiazepines, severe respiratory failure or acute respiratory depression. Bradycardia is a known adverse effect of midazolam and ketamine. Therefore, patients with pre-existing bradycardia are excluded.) | |
5. Currently taking any of the following contraindicated medications: ketoconazole, voriconazole, itraconazole, fluconazole, erythromycin, telithromycin, clarithromycin, saquinavir, nefazodone, diltiazem, verapamil, theophylline | |
6. Active suicidal intention (score of 6 on item 10 [Suicidal Thoughts] on the MADRS) | |
7. Confirmed diagnosis of dementia | |
8. Lifetime history of schizophrenia or schizoaffective disorder; active anorexia nervosa or bulimia nervosa in the past 12 months; alcohol or other substance use disorder (with the exception of nicotine) in the previous six months; any DSM-5 disorder other than a major depressive episode (unipolar or bipolar) as the primary presenting problem | |
9. ECT administered within the last two months | |
10. Pregnancy or inability to confirm use of adequate contraception during the trial | |
11. Breastfeeding women |