Symposium
Session Room 219
Session Room 219
Tuesday, June 17, 02:40 PM – 03:55 PM
Symposium 12: Reformulation, omics-based biomarkers and health economic implications of ketamine in the treatment of depression
The discovery of racemic (R)-ketamine as a rapid-acting antidepressant and FDA approval of its (S)-enantiomer, esketamine, for treatment-resistant depression (TRD) are significant advances in the development of novel neuropsychiatric therapeutics. Esketamine is recognized as a powerful tool for addressing persistent symptoms of TRD compared to traditional oral antidepressants. In contrast, Ketamine has been investigated in different formulations ranging from intravenous to subcutaneous and intranasal routes of administration. If given by injection or intranasal routes, ketamine has strong side effects (e.g. dissociation, sedation) and needs to be given under medical/nursing supervision. This limits the number of patients who can access ketamine treatment. In the first talk, Paul Glue will report on how they recently reformulated ketamine into an extended-release tablet, which maximizes ketamine’s first pass metabolism, and slowed its absorption. In a recent Phase 2 study using this ketamine tablet in patients with TRD (1), they show advantages over IV/SC/IN ketamine including minimal dissociation, sedation and blood pressure changes, with statistically significant antidepressant efficacy vs placebo (mean MADRS difference -6.1 (95% CI 1-11.2), p=0.019) and improved tolerability while most doses were taken at home. Availability of an oral ketamine tablet formulation may expand access to this treatment for TRD patients.
Research on biomarkers associated with antidepressant response to ketamine and esketamine has remained sparse and, to date, has been largely originated and extrapolated from racemic ketamine studies. In this presentation, Bernhard Baune will show results on genetic, proteomic, and metabolomic profiles of (R, S)-ketamine in the treatment of depression. The findings suggest that anti-inflammatory and mitochondrial functions of (R, S)-ketamine’s may play additional roles in exerting antidepressant effects. Moreover, DNA methylation might offer new insights into understanding the mode of action of ketamine. Specifically, his group has recently shown DNA methylation differences between treatment groups of midazolam vs. ketamine in depression after a single dose of administration of ketamine s.c. as part of the KADS trial (2). The findings suggest that the mechanisms of action of (R, S)-ketamine might be beyond the effects via the proposed glutamatergic system alone.
The next presentation expands into the highly under-researched area of pharmacoeconomics of ketamine. Although emerging pharmacological therapies (i.e. ketamine, esketamine, psilocybin) show efficacy in TRD, there is less data on their cost-effectiveness which is important for funding through governments and insurers. Without being subsidised, access to these treatments will be limited. This lack of data is compounded by the fact that TRD affects a substantial proportion of patients with MDD (approximately 30%) and is associated with significant individual and societal burden. To address this important issue, Mary Lou Chatterton and her team completed the first trial-based cost-effectiveness analysis of ketamine versus midazolam administered s.c. twice weekly for 4 weeks (3). Quality-adjusted life-years were significantly greater in the ketamine group vs. the midazolam control group (difference 0.008; 95% CI: 0.003 to 0.014). Total health sector costs were not significantly different (difference -354; 95% CI -954 to 461). This led to ketamine being considered cost-effective compared to midazolam from the health sector perspective.
Research on biomarkers associated with antidepressant response to ketamine and esketamine has remained sparse and, to date, has been largely originated and extrapolated from racemic ketamine studies. In this presentation, Bernhard Baune will show results on genetic, proteomic, and metabolomic profiles of (R, S)-ketamine in the treatment of depression. The findings suggest that anti-inflammatory and mitochondrial functions of (R, S)-ketamine’s may play additional roles in exerting antidepressant effects. Moreover, DNA methylation might offer new insights into understanding the mode of action of ketamine. Specifically, his group has recently shown DNA methylation differences between treatment groups of midazolam vs. ketamine in depression after a single dose of administration of ketamine s.c. as part of the KADS trial (2). The findings suggest that the mechanisms of action of (R, S)-ketamine might be beyond the effects via the proposed glutamatergic system alone.
The next presentation expands into the highly under-researched area of pharmacoeconomics of ketamine. Although emerging pharmacological therapies (i.e. ketamine, esketamine, psilocybin) show efficacy in TRD, there is less data on their cost-effectiveness which is important for funding through governments and insurers. Without being subsidised, access to these treatments will be limited. This lack of data is compounded by the fact that TRD affects a substantial proportion of patients with MDD (approximately 30%) and is associated with significant individual and societal burden. To address this important issue, Mary Lou Chatterton and her team completed the first trial-based cost-effectiveness analysis of ketamine versus midazolam administered s.c. twice weekly for 4 weeks (3). Quality-adjusted life-years were significantly greater in the ketamine group vs. the midazolam control group (difference 0.008; 95% CI: 0.003 to 0.014). Total health sector costs were not significantly different (difference -354; 95% CI -954 to 461). This led to ketamine being considered cost-effective compared to midazolam from the health sector perspective.
02:40 PM – 03:05 PM
25 min
25 min