A Study to Investigate Evoked Potentials as Markers of Ketamine-induced Cortical Plasticity in Patients With Major Depressive Disorder
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Ketamine; Placebo
Intervention description: During Cohorts 1 and 2, a single ketamine 0.5 mg/kg dose will be given as a continuous IV infusion over 40 minutes by use of an electronic syringe infusion pump. The predefined dose and infusion rate/duration should not be adjusted. If a patient is unable to tolerate the study medication, the infusion should be stopped. Within 1 week of completion of the open-label treatment phase, participants can receive a single dose of ketamine 0.5 mg/kg administered as an IV infusion over 40 minutes during an optional open-label treatment phase.; During Cohort 2, a single placebo dose will be given as a continuous IV infusion over 40 minutes by use of an electronic syringe infusion pump. Within 1 week of completion of the double-blind treatment phase, participants can receive a single dose of ketamine 0.5 mg/kg administered as an IV infusion over 40 minutes during an optional open-label treatment phase.
Intervention MeSH terms: Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Major Depressive Disorder; Ketamine; Evoked potentials; Somatosensory evoked potentials; Motor evoked potentials; Cortical plasticity

Summary:

      To evaluate if somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs)
      obtained with electroencephalography (EEG) and electromyography (EMG) can be used to detect
      changes in cortical plasticity in responders to a single IV infusion of ketamine as compared
      to non-responders.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient must be medically stable

          -  Patient must meet Diagnostic and Statistical Manual of Mental Disorders - Fourth
             Edition (DSM-IV) diagnostic criteria for Major Depressive Disorder (MDD), without
             psychotic features, based upon clinical assessment and confirmed by the Mini
             International Psychiatric Interview (MINI)

          -  Patient must have had an inadequate response to at least 2 antidepressants, one of
             which is in the current episode of depression

          -  Patient must have an Inventory of Depressive Symptomatology 30-item Clinician-rated
             (IDS-C30) total score ≥ 34 at Screening and Day -1

          -  Women must be postmenopausal, surgically sterile, or, if heterosexually active,
             practicing a highly effective method of birth control

          -  Men who are heterosexually active with a woman of childbearing potential must agree to
             use a double barrier method of birth control and to not donate sperm during the study
             and for 3 months after receiving the last dose of study drug

        Exclusion Criteria:

          -  Patient has current signs and/or symptoms of liver or renal insufficiency; significant
             cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic,
             rheumatologic, or metabolic disturbances

          -  Patient has a primary DSM-IV diagnosis of current (active) generalized anxiety
             disorder (GAD), panic disorder, obsessive compulsive disorder (OCD), posttraumatic
             stress disorder (PTSD), anorexia nervosa, or bulimia nervosa

          -  Patient has a current diagnosis of bipolar disorder, mental retardation, or cluster b
             personality disorder (e.g., borderline personality disorders, antisocial personality
             disorder, etc)

          -  Patient has a current or prior diagnosis of a psychotic disorder or MDD with psychosis

          -  Patient has not responded to treatment with electroconvulsive therapy (ECT) in the
             current episode of depression

          -  Patient has suicidal ideation with intent to act, or has homicidal ideation/intent,
             during Screening phase per Investigator's clinical judgment

          -  Patient has any significant primary sleep disorder