Intervention: Ketamine
Trial phase: Phase 4
ATC code: N01AX03 | N01AX14 | N06AX27
SMILES: CNC1(c2ccccc2Cl)CCCCC1=O
Sex: All
Age groups: Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 16
Group description: All eligible participants will receive open label ketamine

Ketamine: Ketamine 0.5mg/kg over 40 minutes IV
Eligibility criteria:
Inclusion Criteria: Patients with Depression

Patients will:

be 18-64 years old,
read, understand, and provide written informed consent in English,
meet criteria for a primary psychiatric diagnosis of major depressive disorder for ≥ 4 weeks,
have a history of ≥1 failed medication trial during the current depression
be on a stable antidepressant and psychotherapy regimen for ≥28 days,
maintain a treating doctor who is in agreement with study participation,
have a reliable chaperone accompany them home following the completion of the ketamine infusion day,
be generally healthy, as assessed by medical history, physical examination (including vital signs), clinical laboratory evaluations, and electrocardiogram (EKG),
be of non-childbearing potential or use of an acceptable form of birth control (females only),
be right handed.

Exclusion Criteria: Patients with Depression

Patients will be excluded if any of the following criteria are met:

1) delirium or dementia diagnosis, 2) unstable medical illness or clinically significant laboratory results, 3) history of clinically significant cardiovascular disease or electrocardiogram (EKG) findings, or medical conditions that put the patient at risk for possible cardiac side effects or alter brain morphology (e.g., traumatic brain injury), 4) history of multiple adverse drug reactions, 5) current/past history of psychotic disorders, 6) active substance use disorders (except nicotine and caffeine) within the past six months or past history of ketamine/PCP abuse, 7) requirement of excluded medications that may interact with ketamine, 8) weigh >250 lbs., 9) pregnancy, breastfeeding, or unacceptable means of birth control (females only) 10) presence of MRI contraindications (e.g., presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clips)), 11) current serious suicidal or homicidal risk, or 12) concurrent participation in other research studies.

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Inclusion Criteria: Healthy Controls

Healthy Controls will:

be 18-64 years old,
read, understand, and provide written informed consent in English,
have a reliable chaperone accompany them home following the completion of the ketamine infusion day,
be generally healthy, as assessed by medical history, physical examination (including vital signs), clinical laboratory evaluations, and electrocardiogram (EKG),
be of non-childbearing potential or use of an acceptable form of birth control (females only), and
be right handed.

Exclusion Criteria: Healthy Controls

Healthy controls will be excluded if any of the following criteria are met:

current or past psychiatric diagnosis (excluding phobias), including alcohol or substance abuse or dependence diagnosis (except for nicotine or caffeine),
presence of MRI contraindications (e.g., presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clips)),
presence of medical illness likely to alter brain morphology and/or physiology (e.g., traumatic brain injury),
requirement of excluded medications that may interact with ketamine,
presence of psychiatric disorders in first-degree relatives,
pregnancy, breastfeeding, or unacceptable means of birth control (females only), or
weight >250 lbs.