Key Takeaways
Extended Takeaways
- At 24 hours after the first infusion, pooled onfasprodil 0.16 mg/kg showed a larger placebo-adjusted MADRS benefit than pooled onfasprodil 0.32 mg/kg (−8.25 vs −5.71), suggesting that increasing dose did not improve early antidepressant signal in this study.
- By 48 hours, mean MADRS reductions were −14.94 with pooled onfasprodil 0.16 mg/kg, −15.25 with pooled onfasprodil 0.32 mg/kg, and −18.89 with ketamine; the onfasprodil-ketamine differences were not statistically significant, supporting NR2B modulation as a potentially ketamine-comparable mechanism in the acute window.
- At Week 6, only 2 regimens separated from placebo on MMRM analysis: onfasprodil 0.16 mg/kg biweekly at −6.46 (−11.78 to −1.15; P = .0598) and onfasprodil 0.32 mg/kg weekly at −5.42 (−10.83 to −0.02; P=.0993), which may help guide regimen selection if this agent moves forward.
- Dissociative burden appeared lower with onfasprodil than with ketamine: dissociation was reported in 5 (23.8%) patients in pooled onfasprodil 0.16 mg/kg and 5 (26.3%) in pooled onfasprodil 0.32 mg/kg versus 5 (50.0%) with ketamine, and the mean maximum CADSS change from baseline was ≤5 with onfasprodil versus 10.30 with ketamine.
- Clinicians should expect adverse effects to occur during or soon after infusion rather than later in the day: for onfasprodil, significant AEs began as early as 0 to 0.7 hours for amnesia and dissociation, the maximum time to onset was 4.4 hours, and the maximum time to resolution was 9.2 hours.
- Despite a half-life of approximately 7 hours, antidepressant effects were maintained for up to 2 weeks, indicating a pharmacodynamic effect that outlasts plasma exposure and supporting intermittent rather than daily administration strategies.
