|Inclusion criteria||1. Age 18 to 80 years;|
2. Current major depressive episode according to the DSM-5, ascertained by the MINI;
3. Depression at least moderately severe, defined by a score > 18 on the HDRS17;
4. TRD, defined as insufficient lifetime response to 3 or more different classes of antidepressant drugs, given for at least 4 weeks and in an adequate dose;
5. Stable dose of current antidepressant drug for at least 4 weeks prior to study initiation;
6. Good understanding of spoken and written Dutch.
|Exclusion criteria||1. Meet DSM-5 criteria for current major depressive episode with psychotic features, bipolar disorder, past or current psychotic disorder, past or current moderate or severe substance dependence, or personality disorder as a primary diagnosis;|
2. Recent (within the last 4 weeks) or current use of non-prescribed psychoactive compounds;
3. Recent (within the last 4 weeks) or current use of benzodiazepines in excess of 2 mg lorazepam or equivalent per day;
4. Current electroshock therapy;
5. Active suicidal intent, defined by a score > 2 on item 3 of the HDRS17;
6. Pregnancy or lactation;
7. A relevant somatic disorder, ascertained by physical examination, electrocardiogram, and blood tests;
8. Use of medication that ketamine interacts with on a major level according to the Drug Interactions Checker , including monoamine oxidase inhibitors.