Inclusion Criteria:  Major depressive episode including unipolar and bipolar depression, according to DSM- 5 criteria and MINI-adolescent version (Mini-International Neuropsychiatric Interview; MINI) diagnostic interview. Age 13 to 19 years old. Body weigh ≧ 30 kg. Treatment-resistant depression, which is defined as poor or unsatisfactory response to at least two different antidepressants administered at an adequate dosage and for an adequate treatment duration Still prominent depressive symptoms with at least 4-week treatment of medication treatment or psychotherapy Voluntary patients and their parents or guardians with signed informed consent proved by institutional review board (IRB)  Exclusion Criteria:  Major medical conditions (e.g., head injury, epilepsy, severe renal diseases and cancer). Other axis I psychiatric disorders such as schizophrenia, delusional disorder, organic brain syndrome, and dementia. Pregnancy. Substance abuse in previous 6 months such as cocaine, marijuana, opium, ketamine, PCP (phencyclidine)。 Current use of NMDA receptor antagonist (Amantadine, Rimantadine, Lamotrigine, Memantine, Dextromethorphan) Alcohol abuse / dependence within 6 months. Attempt suicide in hospital. Allergy to ketamine Abnormal liver function in recent 3 months。 Abnormal ECG (i.e.:arrhythmia)。 Fever or infection in recent 5 days。