Ketamine for Treatment Resistant Late-Life Depression

• Status: Completed
• Trial end date: 2020-03-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to examine the effectiveness of a single infusion of ketamine (KET), to determine which dose is optimal 7 days after infusion using Bayesian Adaptive Randomization, and to learn about how ketamine works in the body and brain in persons with late-life treatment resistant depression.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: VA Office of Research and Development
• Treatments: Ketamine; Midazolam

Criteria

Inclusion Criteria:

• Male or female patients, 55 years of age,

• Participants must fulfill DSM 5 criteria for a Major Depressive Episode (Unipolar), based on a structured diagnostic interview, the DSM 5 M.I.N.I. 7.0

• Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration),

• Participants have not responded to two or more adequate trials of FDA-approved antidepressants, determined by Antidepressant Treatment Response Questionnaire (ATRQ) criteria.

• Participants must score 14 or greater on the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), and score 27 on the Montgomery Asberg Depression Rating Scale (MADRS),

• Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document.

Exclusion Criteria:

• Patients currently on fluoxetine,

• History of schizophrenia, schizoaffective disorder or any psychotic disorder, or bipolar disorder,

• Documented history of a psychotic disorder in a first-degree relative,

• Current diagnosis of obsessive-compulsive disorder (OCD) or eating disorder [bulimia nervosa or anorexia nervosa],

• Alcohol or substance use [except nicotine] within the preceding 6 months,

• Patients with any clinically significant personality disorder that would, in the investigator's judgment, preclude safe study participation,

• Patients judged to be at serious and imminent suicidal or homicidal risk,

• Serious, unstable medical illnesses including respiratory [obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics], cardiovascular [including ischemic heart disease and uncontrolled hypertension], and neurologic [including history of severe head injury],

• For study entry, patients must be reasonable medical candidates for ketamine or midazolam infusion, as determined by a board-certified physician co-investigator during study Screening,

• Clinically significant abnormal findings of laboratory parameters [including urine toxicology screen for drugs of abuse], physical examination, or ECG,

• Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg),

• Patients with one or more 11 seizures without a clear and resolved etiology,

• Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening,

• Past intolerance or hypersensitivity to ketamine, or history of recreational use of phencyclidine (PCP) or ketamine,

• Past intolerance or hypersensitivity to midazolam,

• Age-related cognitive decline or mild dementia suggested by a score of < 25 on the Mini-Mental State Examination (MMSE) at Screening,

• Patients taking medications with known activity at the N-methyl-D-aspartate receptor (NMDA) or AMPA glutamate receptor [e.g., riluzole, amantadine, lamotrigine, memantine, topiramate, dextromethorphan, D-cycloserine], or the muopioid receptor,

• Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide,

• Patients who demonstrate > 25% decrease in depressive symptoms as reflected by the QIDS-SR score from Screening to Randomization,

• Patients who have received electroconvulsive therapy (ECT) in the past 6 months prior to Screening,

• Patients currently receiving treatment with vagus nerve stimulation (VNS) or repetitive transcranial stimulation (rTMS).