Introduction

Intranasal esketamine administration demonstrates rapid improvement in symptoms of treatment-resistent depression. Transient adverse effects (dissociative symptoms, sedation, dizziness) that could impact driving performance occur routinely in the hours after esketamine administration.

Objectives

To investigate effects of 84 mg esketamine on on-the-road driving performance.

Methods

Part A used a single-blind, double-dummy, randomized 3-period, cross-over design to compare effects of esketamine vs placebo on next-morning driving. Alcohol (blood alcohol concentration ≤0.05% ) established assay sensitivity. In Part B, esketamine was administered twice weekly, and weekly driving tests were conducted 6h after administraton.

Twenty-seven patients with DSM-5-defined mild-to-moderate major depressive disorder without psychotic features completed a 100-km driving test on a public highway in normal traffic. Primary outcome was Standard Deviation of Lateral Position (SDLP;cm;weaving of car). Part A driving assessments were conducted 18±2 hours post-administration. Part B driving tests were conducted 6±0.5 hours post-treatment.

Results

In Part A, alcohol significantly impaired driving performance: Least-square means (95%CI) for delta SDLP (cm) compared with placebo: [ΔSDLP = +1.83 (1.03;2.62)]. There was no significant difference between esketamine and placebo, [ΔSDLP = -0.23 (-1.04;0.58)]. Weekly driving tests showed no significant differences between placebo baseline SDLP and after esketamine administration over 4 weeks (Day 11: [ΔSDLP = -0.96 (-3.72;1.81)], Day 18: [ΔSDLP = -0.56 (-3.33;2.20)], Day 25: [ΔSDLP = -1.05 (-3.82;1.71)]).

Conclusions

In MDD patients, esketamine did not significantly impair on-road driving performance the next morning following a single dose, or 6 hours after repeated administrations. These results support the label recommendation to not drive on the day of esketamine dosing.