Migraine drug may impair mental alertness
The centrally penetrant, selective serotonin 1F (5‐HT1F) receptor agonist lasmiditan appears to adversely affect driving performance at 1.5 hours postdose, but this effect disappears after 8 hours, as shown in a crossover trial.
Healthy adults were enrolled in two randomized crossover studies. Each study included an active control to establish the sensitivity of detecting residual sedation and resulting driving impairment. The first study included 90 participants and tested lasmiditan (50, 100, and 200 mg), alprazolam (1 mg), and placebo at 1.5 hours postdose. Sixty-eight individuals participated in the second study that tested lasmiditan (100 and 200 mg), diphenhydramine (50 mg, administered 2 hours prior to evaluation), and placebo at 8, 12, and 24 hours postdose.
Driving performance was assessed using a validated 100-km driving simulator, with the primary endpoint being standard deviation of lateral position (SDLP), a measure of lane position control. Blood samples were obtained pre‐ and post-dose to measure lasmiditan plasma concentrations. Assay sensitivity was confirmed by increased SDLP for active comparators at 1.5‐ and 8‐hour time points.
At 1.5 hours after dosing, driving performance was significantly impaired with lasmiditan doses than with placebo. But this difference disappeared at the 8-hour time point. Driving impairment was concentration‐dependent at 1.5 hours but not at 8 hours.
Commonly reported adverse events were related to central nervous system and mild‐to‐moderate in severity.
In light of the findings, the researchers warned patients taking lasmiditan against engaging in potentially hazardous activities requiring complete mental alertness, such as driving a motor vehicle or operating machinery, for at least 8 hours after each dosing.