The Relationship Among Changes in Brain Network Activation in Adult Outpatients With Major Depressive Disorder
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: vortioxetine
Intervention description: Open-label vortioxetine
Intervention MeSH terms: Vortioxetine
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: depression; brain network activation; vortioxetine

Summary:

      The purpose of this study is to explore patterns of Brain Network Activation (BNA) changes
      from baseline to endpoint on 1) efficacy of core symptoms of Major Depressive Disorder (MDD)
      and 2) improvement of cognitive dysfunction with acute treatment with flexible dose
      vortioxetine in adult outpatients with MDD and subjective complaints of cognitive
      dysfunction.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject has single episode or recurrent MDD (acute onset of recurrence of
             recurrent MDD with poor inter-episode recovery) (inter-episode periods cannot meet
             full MDD criteria) as the primary diagnosis according to DSM-IV-TR criteria. The
             current major depressive episode (MDE) will be confirmed using the Mini International
             Neuropsychiatric Interview (MINI V6.0.0).

          -  The subject has a MADRS total score ≥26.

          -  Subject reports subjective cognitive dysfunction (such as difficulty concentrating,
             slow thinking, and difficulty in learning new things or remembering things).

          -  The reported duration of the current MDE is at least 3 months and no longer than 24
             months.

          -  The subject is a man or woman between 18 and 65 years old, inclusive.

          -  Right-handed, normal (corrected) vision, and normal hearing.

        Exclusion Criteria:

          -  The subject has a score of ≥70 on the Digit Symbol Substitution Test (DSST) at the
             Baseline Visit.

          -  Failure to respond to or inability to tolerate an adequate trial of vortioxetine in
             the past.

          -  Exposure to an investigational compound 30 days prior to enrollment

          -  Exposure to any psychoactive or otherwise excluded medication within five half-lives
             of the baseline visit or during the study. Excluded medications include:
             antidepressants, anxiolytics, anticonvulsants, barbiturates, chloral hydrate, lithium,
             antipsychotics, benzodiazepines, hypnotics, monoamine oxidase inhibitors (MAOIs),
             muscle relaxers, triptans, centrally-acting antihistamines, central alpha-2 agonists,
             decongestants, psychostimulants, dopamine agonists, opioid pain medications, oral
             corticosteroids, L-methylfolate, S-adenosyl methionine (SAMe), 5-HTP
             (hydroxytryptophan), St. John's Wort,

          -  The subject has 1 or more of the following:

               -  Primary psychiatric disorder other than MDD as defined in the Diagnostic and
                  Statistical Manual of Mental Disorders 4 Text Revision (DSM-IV-TR) (as assessed
                  by the MINI, Version 6.0.0).

               -  Current or history of attention deficit hyperactivity disorder (ADHD), pervasive
                  developmental disorder, manic or hypomanic episode, schizophrenia, or any other
                  psychotic disorder, including major depression with psychotic features, mental
                  retardation, organic mental disorders, or mental disorders due to a general
                  medical condition as defined in the DSM-IV-TR.

               -  Current diagnosis of alcohol or other substance abuse or dependence (excluding
                  nicotine or caffeine) as defined in the DSM-IV-TR that has not been in sustained
                  full remission for at least 6 months (for abuse) and 12 months (for dependence)
                  prior to Screening.

               -  Positive urine drug screen prior to Baseline.

               -  Presence or history of a clinically significant neurological disorder (including
                  epilepsy).

               -  Neurodegenerative disorder (Alzheimer Disease, Parkinson Disease, multiple
                  sclerosis, Huntington Disease, etc).

               -  Any unstable medical condition as determined by the principal investigator (PI).

               -  Any DSM-IV Axis II disorder that might compromise the study as determined by the
                  PI.

          -  The subject has any other disorder for which the treatment takes priority over
             treatment of MDD or is likely to interfere with study treatment or impair treatment
             compliance.

          -  The subject has physical, cognitive, or language impairment of such severity as to
             adversely affect the validity of the data derived from the neuropsychological tests.

          -  The subject has a significant risk of suicide according to the PI's clinical judgment.

          -  The subject, in the opinion of the PI, poses a risk of harm to others.

          -  The subject has initiated formal cognitive or behavioral therapy, systemic
             psychotherapy within less than 6 months of study screening, or has plans to initiate
             such therapy during the study.

          -  The subject has received electroconvulsive therapy, vagus nerve stimulation, or
             repetitive transcranial magnetic stimulation within 12 months prior to Screening.

          -  The current MDE is considered by the PI to have been resistant to 2 adequate
             antidepressant treatments of at least 6 weeks duration each at the recommended dose.

          -  The subject is pregnant or breastfeeding, or is intending to become pregnant before,
             during, or within 30 days after participating in this study.