Ketamine As an Adjunctive Therapy for Major Depression (2)

Inclusion Criteria: * ≥18 years old. * Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 20 at screening and start of the first infusion. * Voluntary admission for treatment of an acute depressive episode * Meet DSM-5 criteria for a major depressive disorder or bipolar affective disorder (current episode depression). Diagnosis of a major depressive disorder or bipolar affective disorder (DSM-5) will be confirmed by the structured diagnostic Mini International Neuropsychiatric Interview (MINI; updated Version 7 for DSM-5). Exclusion Criteria: * Current involuntary admission. * Medical condition rendering unfit for ketamine/midazolam. * Currently taking any of the contraindicated medications that may alter the pharmacokinetics of ketamine. * Active suicidal intention. * Dementia. * 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. * Electroconvulsive Therapy (ECT) administered within the last two months. * Pregnancy, breastfeeding or considering becoming pregnancy whilst on the trial for up to 12 weeks after last dose or inability to confirm use of adequate contraception during the trial. * Breastfeeding women.