OBJECTIVE: Ketamine is a rapid-acting antidepressant with an incompletely understood mechanism of action. Pharmacometabolomics can identify pathways underlying its effects and response variability. Using data from the Bio-K trial (NCT03156504), a multisite open-label study, we characterised metabolomic signatures of intravenous (IV) racemic ketamine in adults with treatment-resistant depression...
Previous work has identified four correlated factors (depression phenotypes) using the Montgomery-Åsberg Depression Rating Scale (MADRS)- Sadness, Negative Thoughts, detachment/Interest and Activity (IA), and Neurovegetative. We explored treatment responses to ketamine based on these 4 phenotypes in treatment resistant depression (TRD). This is a secondary analysis of data from an open-label...
Treatment-resistant depression (TRD) remains a challenge, but intravenous racemic ketamine offers rapid antidepressant effects. Reliable biomarkers are needed. In this study, we examined kynurenine pathway metabolites and inflammatory cytokines as predictors of ketamine response. The Bio-K study was a multicenter, open-label trial of 74 patients with TRD who received 3 ketamine infusions over...
This nonrandomized, multicenter, open-label clinical trial explored the impact of intravenous (IV) ketamine on cognitive function in adults (n = 74) with treatment-resistant depression (TRD). Patients received three IV ketamine infusions during the acute phase and, if remitted, four additional infusions in the continuation phase (Mayo site). Cognitive assessments using the Repeatable Battery...
We recently became aware of an error in the classification of one study subject's positive treatment response status at the end of the post-continuation phase of this study. We originally reported that all 5 subjects who achieved depressive symptom remission during the acute phase of the study (and thus received 4 weekly continuation phase ketamine infusions) were classified as responders at...
Little is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression. Twelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered...
There is an urgent need for more rapidly effective pharmacotherapies for major depressive disorder and bipolar disorder (BP) that are efficacious and tolerable for depressed patients who respond poorly to conventional treatments. Multiple controlled trials have now demonstrated a rapid, nonsustained antidepressive response to a single intravenous infusion of ketamine. Early controlled studies...