AMPA Receptor Components of the Anti-Depressant Ketamine Response

Looking for adults experiencing depression to participate in paid MRI research

Are you currently experiencing severe depression? Have you tried antidepressants before without success? Would you like to participate in a research study? Help us understand the effects of the rapid antidepressant ketamine on the brain and earn up to

$720 compensation for your time.

Study involves:

• A physical examination
• Providing blood for genetic analysis
• Thinking tasks
• Receiving ketamine as an experimental treatment for your depression
• Taking a study drug that may change the effects of the ketamine or your depressive symptoms
• Up to 4 MRI scans
• Speaking on the phone with study staff about how you are feeling after receiving ketamine

Participants must be:

• 18-60 years of age
• Right-handed
• Currently experiencing severe depression
• Have tried at least one antidepressant treatment in the past
• Willing to abstain from using recreational drugs and alcohol for 1 week before each MRI scan

Participants must NOT:

• Have metal in their body that prevents them from getting an MRI scan
• Be currently abusing drugs or alcohol

If you have not received ketamine as a treatment for depression, we will ask you to try ketamine in an outpatient hospital setting for additional compensation.

For more information and to find out if you are eligible, please contact Leslie Maldonado at nempro.lab@yale.edu or call (203) 508-7787.

Inclusion Criteria:

• Participants between the ages of 18-60
• Right-handed as determined by the Edinburgh Handedness Inventory
• Current depression as indicated by a score greater than 17 on the full Hamilton Depression Rating Scale
• Anti-depressant resistant depressive symptoms, defined by a history of failure of one or more adequate anti-depressant trials
• Individuals who have previously received ketamine must have had a positive response. Individuals who report reduced depressive symptoms will be treated as ketamine responders and entered directly into the closed label trial.
• Participants will meet DSM-5 Criteria for Major Depressive Disorder as determined by the SCID-5
• All participants given ketamine must be engaged in treatment outside of the research protocol. Those who are not currently in treatment may be referred for treatment.
• Individuals who are receiving pharmacotherapy for depression must have been receiving the current medication and dose for 4 weeks. In addition, they should have a plan to continue the current regime of pharmacotherapy for the duration of the trial.
• Individuals who are receiving psychotherapy must have been in treatment for four weeks and should have a plan to continue the current regime of psychotherapy for the duration of the trial.
• Willing to refrain from caffeine, drug and alcohol use for one week prior to each MRI session
• Females will be included if they are not pregnant or breastfeeding and agree to utilize a medically accepted birth control method (to include oral, injectable, or implant birth control, condom, diaphragm with spermicide, intrauterine device, tubal ligation, abstinence, or partner with vasectomy). Women who are surgically sterile or post-menopausal with cessation of menses for at least one year are not required to use birth control.

Exclusion criteria:

• A score on the Columbia Suicide Severity Rating Scale in the “intent” or “intent with plan” categories

• Neurological disorder excluding migraine headaches or head injury that is more than mild. Individuals with migraines will not complete any ketamine infusion visits within 24 hours of a migraine.
• Current therapeutic treatment with ketamine
• Current treatment with topiramate, memantine, or barbiturates within two weeks of randomization.
• Daytime use of benzodiazepines
• Current treatment with monoamine oxidase inhibitors within 4 weeks of randomization
• Treatment with a vagal nerve stimulator, ECT or deep brain stimulation within two weeks of randomization

• Current psychosis
• History of psychosis other than psychotic experiences congruent with depressed mood during a period of depression
• Insulin-dependent diabetes or non-insulin dependent diabetes that is poorly controlled
• Other major medical disorder unless cleared by a study physician
• History of violence
• A positive on screening urine drug test or, at the study physicians’ discretion, on any drug screens given before the scans.