Ketamine for Depression and Alcohol Dependence

Inclusion Criteria:

1. Male or female (post-menopausal, surgically sterile or negative pregnancy test at screening and agreement to utilize a medically-approved birth control method including complete abstinence during the testing period) between the age of 21 and 65 years old.
2. Able to provide written informed consent according to the WHVA and Yale HIC guidelines.
3. Medically and neurologically healthy on the basis of medical history, physical examination, EKG, and screening laboratories (CBC w/ differential, basic metabolic profile including BUN/creatinine, TSH, fT4, AST, ALT, GGT, total protein, albumin, vitamin B12, folate, VDRL, HIV, hepatitis B and C, urinalysis, HCG, and urine toxicology screen). Predefined exclusion criteria are identified, e.g. LFTs \> 3x upper limit of normal. Individuals with stable medical problems that do not have direct CNS effects, e.g. hypertension and diabetes mellitus, or interfere with medications administered, e.g. oral hypoglycemics, may be included if their medications have not been adjusted in the month prior to study enrollment.
4. Current DSM-IV-TR major depressive episode (MDE) by structured clinical interview (SCID) and a MADRS score ¬\>20.
5. Current DSM-IV-TR alcohol dependence with one heavy drinking day (\> 4 standard drinks/session for men and \> 3 standard drinks/session for women) in the last 3 weeks.
6. Abstinent from drinking for \> 5 days prior to receiving ketamine.
7. No current psychotropic medications (excluding benzodiazepines during alcohol detoxification if needed) in last 2 weeks (4 weeks for fluoxetine).
8. Individuals who have completed a detoxification program and who are at least 5 days past their last drink.

Exclusion Criteria:

1. Unstable medical condition or medical problem with known CNS effects, e.g. uncontrolled hypertension (SBP≥170 and/or DBP≥100) or confirmed history of alcohol-withdrawal seizures.
2. Active suicidal ideation, intent or plan.
3. Active DSM-IV-TR substance use disorder in past three months (other than an alcohol or nicotine use disorder).
4. Prior diagnosis of a DSM-IV-TR psychotic spectrum disorder, e.g. schizophrenia, schizoaffective disorder, bipolar I d/o with psychotic features, MDD with psychotic features.