The effects of intranasal esketamine on on-road driving performance in patients with major depressive disorder or persistent depressive disorder

Francis M Dijkstra, Aurora Jae van de Loo, Smedra Abdulahad, Else R Bosma, Mitch Hartog, Hendrikje Huls, Dianne C Kuijper, Esther de Vries, Bhavna Solanki, Jaskaran Singh, Leah Aluisio, Peter Zannikos, Frederik E Stuurman, Gabriël E Jacobs, Joris C Verster, Francis M Dijkstra, Aurora Jae van de Loo, Smedra Abdulahad, Else R Bosma, Mitch Hartog, Hendrikje Huls, Dianne C Kuijper, Esther de Vries, Bhavna Solanki, Jaskaran Singh, Leah Aluisio, Peter Zannikos, Frederik E Stuurman, Gabriël E Jacobs, Joris C Verster

Abstract

Background: Intranasal esketamine demonstrates rapid improvement of depressive symptoms. However, transient adverse effects (dissociation, sedation and dizziness) may occur, which could impact driving performance.

Aims: To evaluate the effects of 84 mg intranasal esketamine on driving performance in unipolar major depressive disorder (MDD) or persistent depressive disorder (PDD) patients.

Methods: The study consisted of two parts. Part A was a single-blind, double-dummy, randomized three-period, cross-over study to compare effects of esketamine versus placebo on next morning driving, 18 ± 2 h post-treatment. Alcohol was administered to demonstrate assay sensitivity. In Part B, same-day driving, 6 ± 0.5 hours post-treatment, was assessed during twice weekly esketamine administration for 3 weeks. Twenty-seven patients with mild-to-moderate MDD or PDD without psychotic features completed a 100 km on-the-road driving test on a public highway in normal traffic. The primary outcome was standard deviation of lateral position (SDLP; cm; weaving of car).

Results: In Part A, alcohol impaired driving performance compared to placebo: Least-square means (95% CI), p-value for delta SDLP (cm) compared with placebo: (ΔSDLP = + 1.83 (1.03; 2.62), p < 0.001), whereas esketamine did not: (ΔSDLP = -0.23 (-1.04; 0.58), p = 0.572). In Part B, weekly driving tests showed no differences between placebo baseline SDLP and after esketamine administration over 3 weeks: Day 11: (ΔSDLP = -0.96 (-3.72; 1.81), p = 0.493), Day 18: (ΔSDLP = -0.56 (-3.33; 2.20), p = 0.686) and Day 25: (ΔSDLP = -1.05 (-3.82; 1.71), p = 0.451).

Conclusions: In this study, esketamine did not impair on-road driving performance the next morning following a single dose, or on same day after repeated administration.

Trial registration: ClinicalTrials.gov NCT02919579.

Keywords: Major depressive disorder; SDLP; driving; esketamine nasal spray; persistent depressive disorder.

Conflict of interest statement

Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Over the past 36 months, Joris Verster has acted as a consultant for KNMP, Mentis, More Labs, Red Bull, Sen-Jam Pharmaceutical and Toast!. Bhavna Solanki and Peter Zannikos are employees of Janssen. Jaskaran Singh and Leah Aluisio were employees of Janssen when the study was conducted. The other authors have nothing to declare.

Figures

Figure 1.
Figure 1.
Schematic overview of study.
Figure 2.
Figure 2.
Schematic representation of SDLP.
Figure 3.
Figure 3.
CONSORT diagram.
Figure 4.
Figure 4.
Mean (SD) total MADRS score before (pre) and 20–24 h after (post) administration of single-dose intranasal placebo with oral placebo or oral alcohol, or single-dose 84 mg intranasal esketamine with oral placebo (Part A).
Figure 5.
Figure 5.
Mean (SD) total MADRS score prior to each dose of 84 mg intranasal esketamine on subsequent study visits (Part B).

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Source: PubMed

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