Ketamine for Severe Adolescent Depression: Intermediate-term Safety and Efficacy

Inclusion Criteria: 1. Male or female ages 13-17 years 2. Meet DSM-5 (Diagnostic and Statistical Manual 5 ) criteria for Major Depressive Disorder by structured interview (MINI-KID) 3. Children's Depression Rating Scale, Revised CDRS score ≥40 at screening 4. Failure to achieve remission with at least 2 antidepressant trials (e.g. SSRI, SNRI or TCA), meaning at least 6 weeks at therapeutic dosing, including at least 4 weeks of stable dosing 5. Stable psychiatric medications and doses for the month prior to enrollment. Subjects may continue to engage in any ongoing psychotherapy. 6. Medically and neurologically healthy on the basis of physical examination and medical history. 7. Parents able to provide written informed consent and adolescents must additionally provide assent. Exclusion Criteria: 1. History of psychotic disorder, manic episode, autism spectrum disorder diagnosed by MINI-KID 2. History of substance dependence diagnosis by MINI-KID (excluding tobacco) or positive urine toxicology. 3. Intellectual disability (IQ\<70) per medical history 4. Pregnancy (urine pregnancy tests on the day of infusions for menstruating girls) or lactation 5. Prior treatment with ketamine for depression or prior recreational use of ketamine. 6. Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.