Ketamine in Adolescents With Treatment-Resistant Depression

Inclusion Criteria: * Male and female adolescents aged 12 to 18 years. * Presence of recurrent major depression without psychotic features confirmed by the Kiddie-Schedule for Affective Disorders and Schizophrenia - Parent and Lifetime Version (Kaufman et al., 1997). * Current depression severity measured by the Children's Depression Rating Scale (CDRS) (Poznanski, 1985) raw score greater than or equal to 36 at screening and the day ketamine is due to be received for the first time. * Current depressive episode resistant to treatment, defined as failure to achieve remission (elimination of symptoms and restoration of pre-morbid psychosocial functioning) from at least 2 antidepressant trials of different pharmacological classes. Systematic evaluation of previous antidepressant trials will be assessed by using the Antidepressant Treatment History Form (Sackeim, 2001). * If present, current antidepressant medication treatment must be dose stable for at least 2 months prior to beginning the study. (Patients will continue with current antidepressant treatment throughout the study. Based on our experience in current research at the VA Medical Center using serial ketamine for adult TRD, patients have shown positive results while continuing their current antidepressant treatment.) Exclusion Criteria: * Inability to speak English * Inability or unwillingness to provide written informed consent * A history of Mental Retardation or any Pervasive Developmental Disorder * Current or lifetime diagnosis of schizophrenia, schizoaffective disorder, or psychosis Not Otherwise Specified. * Family history with a first degree relative with schizophrenia, schizoaffective disorder, or psychosis Not Otherwise Specified. * Diagnosis of seizures or other neurological disorders. * Comorbid diagnosis of substance abuse or dependence, current or past. * Clinically unstable medical illness. * Current use of the following medications: any barbiturates, any narcotics, any non-benzodiazepine hypnotics at doses higher than zolpidem 10 mg qhs or equivalent for insomnia. * For women: pregnancy (confirmed by baseline lab test). * The presence of any MRI contra-indications such as MRI-incompatible metals in the body or claustrophobia.