Clinical Trial: Efficacy of Repeated Ketamine Infusions for Treatment-resistant Depression
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Intravenous Sub-anesthetic Ketamine Treatment in Treatment-Resistant Depression
Brief Summary: About one-third of depressed patients will not get better after multiple antidepressant treatments. This situation put a high burden on patients with depression due to worsening quality of life and increasing health care costs. Difficult-to-treat depression might be even worse among Veterans given that the frequency of depressive symptoms is 2 to 5 times higher than among the general US population. A breakthrough discovery happened in recent years when investigators found that one infusion from an old anesthetic named ketamine showed high efficacy and rapid antidepressant effect (sometimes within hours) but lasted only up to a week. The investigators propose to study if multiple infusions of ketamine can provide greater and longer antidepressant effects than one infusion. If that is the case, multiple infusions could be an alternative to relieve depressive symptoms that do not response to multiple antidepressant drugs.
Detailed Summary: Recent studies have found rapid and highly efficacious antidepressant effects of a single ketamine infusion in treatment-resistant depression (TRD). However, a single infusion appears insufficient to maintain response as most patients return to previous depressive state within a week. The strategy of multiple infusions to increase efficacy and sustain antidepressant effects has not yet been systematically evaluated in an randomized control trial (RCT). The proposed study is a one-center, interventional, efficacy study designed to determine antidepressant outcomes of serial ketamine infusions compared to a single ketamine infusion among Veterans with TRD. The investigators have hypothesized that six infusions will be superior to a single infusion of ketamine in both decreasing severity of depressive symptoms and maintaining response. Participants will be male/female Veterans (18 to 75 years old) of any era or military background who suffer from TRD defined as failure to achieve remission from at least 2 antidepressant trials of different pharmacological classes. Potential participants will be recruited from Mental Health clinics and screened for eligibility using a two stage process (phone/chart review, followed by interview). Exclusion criteria includes post-traumatic stress disorder, psychosis-related disorder, bipolar disorder, alcohol/substance use disorder 6 months prior to screening; unstable medical illness; serious/imminent suicidal/homicidal risk; Parkinson's disease, dementia, seizures; traumatic brain injury; contraindicated medications (e.g., MAO inhibitors, barbiturates); received electroconvulsive therapy (ECT) during current episode; pregnancy/nursing. Baseline assessments will be completed 1-2 weeks prior to starting treatment. Participants will be randomly assigned to one of two parallel treatment conditions: 1) six ketamine infusions at 0.5 mg/kg or 2) single ketamine infusion at 0.5 mg/kg preceded by five midazolam infusions at 0.045 mg/kg. Midazol
Sponsor: VA Office of Research and Development
Current Primary Outcome: the efficacy of a single vs. six ketamine infusions in change from baseline in Montgomery- sberg Depression Rating Scale (MADRS) score after 12 days of treatment. [ Time Frame: 13 days ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Antidepressant response defined as >50% decrease in MADRS baseline score [ Time Frame: 13 days ]
- Remission defined as MADRS score 9 [ Time Frame: 13 days ]
- Comparing the durability of antidepressant effect of a single vs. six ketamine infusions from post-infusion response to occurrence of relapse <50% of baseline MADRS score [ Time Frame: 6 months ]
Original Secondary Outcome: Same as current
Information By: VA Office of Research and Development
Dates:
Date Received: January 29, 2015
Date Started: April 1, 2015
Date Completion: March 2019
Last Updated: March 2, 2017
Last Verified: March 2017
