Safety and Efficacy of Levomilnacipran ER in Adolescent Participants With Major Depressive Disorder

Key Inclusion Criteria: * Male or female outpatients;12-17 years of age * Meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for MDD, confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children--Present and Lifetime (K-SADS-PL) * Score ≥ 40 on the Children's Depression Rating Scale-Revised (CDRS-R) at Visits 1 and 2 * Clinical Global Impressions-Severity (CGI-S) score ≥ 4 at Visits 1 and 2 * Reliable caregiver * Physical examination, vital signs, clinical laboratory tests, and electrocardiogram (ECG) normal or not clinically significant Key Psychiatric Exclusion Criteria: * DSM-IV-TR-based diagnosis of an axis I disorder other than MDD that is the primary focus of treatment * Mental retardation or amnestic or other cognitive disorders * Significant suicide risk: * Suicide attempt within the past year OR * Investigator judgment (based on psychiatric interview and Columbia-Suicide Severity Rating Scale (C-SSRS)) Key Treatment-Related Exclusion Criteria: * Allergy, intolerance, or hypersensitivity to levomilnacipran, milnacipran, fluoxetine, or any other selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI) * Use of prohibited concomitant medication that cannot be discontinued Other Key Medical Exclusion Criteria: * Any current medical condition that might interfere with the conduct of the study, confound the interpretation of study results, or affect participants safety * Liver enzyme tests aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 2X the upper limit of normal (ULN) * Clinically significant cardiovascular disorders * Seizure disorder or risk of seizure * Drug or alcohol abuse or dependence (within the past year) * Positive urine drug screen or blood alcohol