a study to investigate evoked potentials as markers of ketamine-induced cortical plasticity in patients with major depressive disorder

Conditions: Major Depressive Disorder

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.

this study will be conducted in patients with major depressive disorder (mdd) and divided into 2 sequential cohorts. cohort 1 will be conducted in 12 patients at a single center. for each patient, there will be up to 4 sequential phases: a screening phase of up to 6 weeks, an open-label treatment phase of up to 4 weeks, an optional open-label treatment phase of up to 1 week, and a follow-up phase of up to 1 week (if applicable). cohort 2 will be conducted in 20 patients and will be a multicenter, double-blind (neither physician nor patient knows the treatment that the patient receives), randomized (the study drug is assigned by chance), placebo-controlled (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) design. for each patient, there will be up to 4 sequential phases: a screening phase of up to 6 weeks, a double-blind treatment phase of up to 4 weeks, an optional open-label treatment phase of up to 1 week, and a follow-up phase of up to 1 week (if applicable). the total study duration for each patient will be maximally about 12 weeks. participant safety will be monitored throughout the study.

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

Keywords: major depressive disorder ketamine evoked potentials somatosensory evoked potentials motor evoked potentials cortical plasticity