Table 1 Inclusion and exclusion criteria for participants

Inclusion criteria

 • Ability to freely provide written informed consent before initiation of study related procedures.

 • Inpatients or outpatients referred to and eligible for standard ECT. Willing to accept randomization to either ECT or IV ketamine arms.

 • Males and females between 18 and 70 years of age.

 • Meet Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) [23] criteria for MDD or BP without psychotic symptoms as confirmed by the MINI International Neuropsychiatric Interview (MINI) [24].

 • Currently in a MDE confirmed by the MINI.

 • Montgomery-Åsberg Depression Rating Scale (MADRS) [22] total score of ≥26 at screening and at randomization, with no more than 20% improvement between these two visits.

 • Body mass index < 35.

 • Montreal Cognitive Assessment (MOCA) [25] score ≥ 24.

 • Ability to understand and comply with study requirements, as judged by the investigator(s).

Exclusion criteria

 • Depression secondary to stroke, cancer or other medical illnesses.

 • Prior or current substance abuse or dependence (except for caffeine or nicotine dependence) and/or recent history (last 12 months) of current alcohol abuse or dependence, as defined by DSM-5 criteria [23].

 • A positive toxicology screen for drugs that are not prescribed.

 • Pregnant, breastfeeding, or of childbearing potential and not willing to use an approved method of contraception during the study.

 • Evidence of clinically relevant disease or unstable medical illness.

 • Clinically significant deviation from reference ranges in clinical laboratory tests.

 • Clinically significant electrocardiogram results as judged by the investigator(s) or cardiologist.

 • History of seizure disorder, except febrile convulsions.

 • Known history of intolerance or hypersensitivity to ketamine.