Biomarkers of Antidepressant Treatment in Adolescents With Major Depression (The Adolescents MDD Study)

Inclusion Criteria: * Outpatients with non-psychotic, unipolar Major Depressive Disorder (MDD) based on the K-SADS-PL * A score of ≥ 45 on the Children's Depression Rating Scale-Revised (same threshold as TADS). As with the TADS trial, depressed mood must have been present in at least 2 of 3 contexts (home, school, among peers) for at least 6 weeks prior to consent. * Age range: 14-18. * Patients with suicidal ideation are eligible only if the thoughts of death or of life not being worth living are not accompanied by a plan or intention for self-harm. Exclusion Criteria: * Subjects will have no unstable medical illness that would prevent completion of participation in the trial (determined as needed from physical examination, ECG, laboratory safety tests, as well as a review of systems). Other specific exclusionary criteria also are based on the BRITE-MD parameters, and include: 1. mentally or legally incapacitated, unable to give informed consent; 2. meets DSM-IV criteria for anorexia nervosa, bulimia nervosa, obsessive-compulsive disorder, any cognitive disorder, bipolar disorder, psychotic disorder, or major depression with psychotic features; 3. MMSE (Folstein et al., 1975) score ≤ 24; 4. evidence of drug dependency or substance abuse within the preceding nine months; 5. stable and in remission on current psychotropic medication(s); 6. any ECT within the past six months; 7. failure to tolerate FLX or treatment failure with an adequate trial of FLX in the current episode; 8. FLX would be contraindicated (e.g., hyponatremia with a prior SSRI); 9. treatment with an MAOI within the past four weeks; 10. any medical illness severe enough to significantly affect brain function or to interfere with interpretation of study results; 11. history of seizures, brain surgery, skull fracture, significant head trauma, or abnormal EEG; 12. psychiatric hospitalization indicated (e.g., imminent danger to self or others); 13. initial QEEG recording is contaminated with artifact so that determination of the biomarker is precluded; 14. use of medications known to affect brain function (e.g., antidepressants, anticonvulsants/mood stabilizers, anticholinergics, antipsychotics, benzodiazepines - same list as in BRITE-MD). Based on the TADS trial, we will also exclude for concurrent diagnoses of attention-deficit hyperactivity disorder managed with psychostimulants, pervasive developmental disorder, and mental retardation (mild, moderate, severe, or profound); 15. subject is currently pregnant, or is of child-bearing potential and not using a medically acceptable means of birth control (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy).