Background The effect of intranasal esketamine on cognitive functioning in healthy participants is assessed in this study. Methods Twenty-four participants (19-49 years) were randomized to one of two treatment sequences in which either esketamine 84 mg or placebo was intranasally administered in a double-blind, two-period crossover design. Primary measures included five tests of Cogstate ® computerized test battery assessed at 1 h predose and 40 min, 2, 4, and 6 h postdose. Secondary measures included the Mental Effort Scale, Karolinska Sleepiness Scale (KSS), and safety. Results Esketamine was associated with significant cognitive performance impairment at 40 min postdose for all five Cogstate® tests (Detection p = 0.0011, Identification p = 0.0006, One-Card Learning p = 0.0040, One Back p = 0.0017, and Groton Maze Learning Test p < 0.0001) versus placebo. In contrast, performance on these tests did not differ significantly between esketamine and placebo at 2, 4, or 6 h postdose. Secondary outcomes indicated a significant, transient increase from baseline under esketamine versus placebo at 40 min postdose on the Mental Effort Scale and at 40 min and 2 h postdose on KSS (p < 0.0001 for both); however, no significant difference was observed on these outcomes between esketamine and placebo at later timepoints. The most commonly reported adverse events were dizziness (67%), nausea (37.5%), disturbance in attention (29.2%), and fatigue (29.2%); the majority were considered mild in severity. Conclusions Esketamine was associated with cognitive performance decline, and greater effort was required to complete the test battery versus placebo at 40 min postdose, which returned to placebo-comparable levels by 2 h postdose. Trial registration: ClinicalTrials.gov identifier: NCT02094378

The aim of this study was to examine efficacy and tolerability of eletriptan in patients switched from barbiturate-containing combinations (Fiorinal), Fioricet. Migraineurs (n = 160) meeting IHS criteria, with unsatisfactory response in the past year to butalbital-containing combinations, treated up to 16 attacks over 3 months with eletriptan 40 mg. Assessments included headache response and pain-free rates and functional impairment at baseline and 2 h postdose, and global ratings of treatment satisfaction at 24 h. At 2 h postdose, average headache response and pain-free rates were 71% (95% CI, 69-74%) and 37% (95% CI, 35-40%), respectively; 68.5% of patients (95% CI, 65-72%) reported functional response. Within-patient analysis found no efficacy diminution over time (no tolerance). Average headache recurrence rate was 20% (95% CI, 18-23%). Eletriptan was well-tolerated; 6 (3.7%) patients discontinued due to adverse events. There were no serious treatment-related adverse events. We conclude that in poor responders to butalbital-caffeine combinations, switching to eletriptan 40 mg was well-tolerated and efficacious.

No abstract

No abstract