Trial Parameters
Brief Summary
Clinical depression often includes a pessimistic view of things which have happened in the past and an impairment in the ability to experience pleasure or looking forward to things. A licensed drug called ketamine affects the levels of glutamate, a chemical messenger in the brain, and has been used as a treatment particularly for depression which hasn't got better with other types of medication. Glutamate plays a role in learning and memory so the investigators are interested in understanding how ketamine can affect how people with depression remember past negative and positive memories and how they experience reward. The investigators are conducting a study in depressed participants who did not improve with the standard antidepressant treatment to expand our understanding on how ketamine can influence memory, the way people understand emotions and learn from rewards and punishments. Study participants will undergo medical and psychiatric health screening, drug administration (ketamine or saline), questionnaires and computer tasks before and after the administration of the study drug, and an MRI scan after administration of the drug. MRI is a type of brain scan that allows us to see how the brain responds during for example memories of things which have happened in the past. This project will help us understand how NMDA antagonists may work in depression.
Eligibility Criteria
Inclusion Criteria: * Willing and able to give informed consent for participation in the study * Sufficiently fluent English to understand and complete the tasks * Registered with a GP and consents to GP being informed of participation in the study 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. * 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. * 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. Acceptable methods of contraception include: * Condoms * Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition o