Antidepressant Discontinuation in Treatment Resistant Depression

Eligibility Criteria

• * Subjects must be a man or woman 18 to 70 years of age, inclusive.
• * Subject must meet criteria for a major depressive disorder as confirmed by the Mini International Neuropsychiatric Interview \[MINI\].
• * Subjects must have a current Treatment-Resistant Depression as defined below.
• * Subjects must have been taking serotonergic antidepressants (serotonin reuptake inhibitor or monoamine oxidase inhibitor) for at least 2 years but not more than 4 years, and have failed 2 previous medication trial for the current episode. Current Montgomery-Åsberg Depression Rating Scale \[MADRS\] score must be equal to or more than 25.
• * Subject must be medically stable.
• * Female subjects must have a negative urine pregnancy test at screening, and agree to avoid pregnancy during the study.
• * Each subject must sign an informed consent form indicating that he/she understands the purpose of the study and the procedures required and are willing to participate in the study.
• * Subject must be able to participate in symptom measurement.
• * Subject has a current Diagnostic and Statistical Manual of Mental Disorders-5 \[DSM-5\] diagnosis of bipolar disorder or has a positive screening for bipolar disorder by Mini International Neuropsychiatric Interview \[MINI\] or Mood Disorder Questionnaire \[MDQ\].
• * Subject has a current DSM-5 diagnosis of schizophrenia, schizoaffective disorder, autistic disorder, or intellectual disability.
• * Subject has a substance use disorder (except for nicotine or cannabis) within 3 months prior to screening or has a positive drug screen test for any recreational drugs at the time of screening with the exception of Cannabis.
• * Subject has evidence of any clinically significant, unstable medical problems that may create a safety risk for a subject, interfere with study participation, or make results difficult to interpret.
• * Subject is at imminent risk of suicide according to the investigator's clinical judgment and/or a Columbia-Suicide Severity Rating Scale (C-SSRS) 3 or more at any time in the study.
• * Subject is a woman who is pregnant, breast-feeding or planning to become pregnant while enrolled in the study.
• * Subject has any condition (according to the investigator) for which participation will not be the best interest for the subject or it can prevent, limit or confound the protocol-specified assessments.