THINC-it Vortioxetine - Sensitivity to Change

MDD Population

Inclusion Criteria

• The participant is able and willing to provide informed consent.
• The participant is male or female 18-65 years of age.
• The participant has received a current diagnosis of a major depressive episode (MDE) as part of MDD as per DSM-5 criteria.
• The participant's current MDE is confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I 5.0.).
• The participant is an outpatient of a psychiatric setting.
• The participant has a MADRS score ≥ 26 at screening and baseline.
• The participant's reported duration of the current MDE is at least 3 months.
• At least one prior major depressive episode validated by previous treatment (e.g., guideline-informed pharmacotherapy and/or manual-based psychotherapy).
• All participants will be screened for cognitive impairment based on DSST performance (pen-and-paper version) with a maximum baseline score of 70 correct symbols entered to avoid ceiling effects.

Exclusion Criteria

• Current alcohol and/or substance use disorder.
• Presence of comorbid psychiatric disorder other than MDD that is a focus of clinical concern as confirmed by the M.I.N.I 5.0.
• Medications approved and/or employed off-label for cognitive dysfunction (e.g., psychostimulants).
• Any medication for a general medical disorder that, in the opinion of the investigator, may affect cognitive function (e.g., corticosteroids, beta-blockers).
• Use of benzodiazepines within 12 hours of cognitive assessments.
• Consumption of alcohol within 8 hours of cognitive assessments.
• Recent use of marijuana as determined by a toxicology screen.
• Physical, cognitive, or language impairments sufficient to adversely affect data derived from cognitive assessments.
• Diagnosis reading disability or dyslexia.
• Clinically significant learning disorder by history.
• Electroconvulsive therapy (ECT) in the last 6 months.
• History of moderate or severe head trauma (e.g., loss of consciousness for >1 hour), other neurological disorders, or unstable systemic medical diseases that in the opinion of the investigator are likely to affect the central nervous system.
• Pregnant and/or breastfeeding.
• Received investigational agents as part of a separate study within 30 days of the screening visit.
• Actively suicidal or evaluated as being a suicide risk (a score of > 4 on the MADRS and/or per clinical judgment using the Columbia-Suicide Severity Rating Scale).
• Currently receiving treatment with Monoamine Oxidase Inhibitors (MAOIs) anti-depressants, antibiotics such as linezolid, or intravenous methylene blue.

Healthy Control Population

Inclusion Criteria

• No current or past history of mental disorder as evidenced by the M.I.N.I. 5.0 for DSM-IV.
• No first-degree relative with an established diagnosis by a healthcare provider of a mood or psychiatric disorder.
• No unstable medical disorders.

Exclusion Criteria

• Use of any medication for a general medical disorder and/or condition that, in the opinion of the investigator, may affect cognitive function (e.g., corticosteroids, beta-blockers).
• Pregnant and/or breastfeeding.
• Consumption of alcohol within 8 hours of THINC-it tool administration.
• Recent use of marijuana as determined by a toxicology screen.