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. 2021 Jan;36(1):1-12.
doi: 10.1002/hup.2762. Epub 2020 Oct 1.

Driving performance and neurocognitive skills of long-term users of sedating antidepressants

Nick N J J M van der Sluiszen  1 , Annemiek Vermeeren  1 , Joke H van Dijken  2 , Aurora J A E van de Loo  3   4 , Janet L Veldstra  2 , Dick de Waard  2 , Joris C Verster  3   4   5 , Karel A Brookhuis  2 , Johannes G Ramaekers  1
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Driving performance and neurocognitive skills of long-term users of sedating antidepressants

Nick N J J M van der Sluiszen et al. Hum Psychopharmacol. 2021 Jan.

Abstract

Objective: To assess driving performance and neurocognitive skills of long-term users of sedating antidepressants, in comparison to healthy controls.

Methods: Thirty-eight long-term (>6 months) users of amitriptyline (n = 13) and mirtazapine (n = 25) were compared to 65 healthy controls. Driving performance was assessed using a 1-h standardised highway driving test in actual traffic, with road-tracking error (standard deviation of lateral position [SDLP]) being the primary measure. Secondary measures included neurocognitive tasks related to driving. Performance differences between groups were compared to those of blood alcohol concentrations of 0.5 mg/ml to determine clinical relevance.

Results: Compared to controls, mean increase in SDLP of all antidepressant users was not significant, nor clinically relevant (+0.75 cm, 95% CI: -0.83 cm; +2.33 cm). However, users treated less than 3 years (n = 20) did show a significant and clinically relevant increase in SDLP (+2.05 cm). No significant effects were observed on neurocognitive tasks for any user group, although large individual differences were present. Most results from neurocognitive tests were inconclusive, while a few parameters confirmed non-inferiority for users treated longer than 3 years.

Conclusion: The impairing effects of antidepressant treatment on driving performance and neurocognition mitigate over time following long-term use of 3 years.

Keywords: antidepressants; driving performance; long-term use; neurocognition; on-the-road driving.

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Conflict of interest statement

J.C. Verster has received grants from Janssen, Nutricia, Red Bull, Sequential, Takeda, and acted as a consultant/advisor for 82Labs, Canadian Beverage Association, Centraal Bureau Drogisterij bedrijven, Clinilabs, Coleman Frost, Danone, Deenox, Eisai, Janssen, Jazz, Purdue, Red Bull, Sanofi‐Aventis, Sen‐Jam Pharmaceutical, Sepracor, Takeda, Transcept, Trimbos Institute, Vital Bevrages and ZBiotics. A. Vermeeren and J.G. Ramaekers have received funding over the last 4 years from pharmaceutical companies (Eisai, Jazz, Merck and Transcept).

Figures

FIGURE 1
FIGURE 1
Schematic drawing of the highway driving test. The standard deviation of lateral position (SDLP) is an index of road tracking error or ‘weaving’. Drugs that induce sleepiness or sedation cause loss of vehicle control, leading to increased road tracking error. Figure and description taken with permission from van der Sluiszen et al. (2019)
FIGURE 2
FIGURE 2
Hypothetical example of the qualification of clinical relevance of performance differences between antidepressant users and controls. The dotted line indicates the change in performance after alcohol intake (relative to placebo). A (drug‐induced) change in performance will be classified as inferior when the 95% CI includes the alcohol criterion but not zero (A—inferiority). Non‐inferiority is concluded when the 95% CI does not include the alcohol criterion (B—non‐inferiority). If the 95% CI includes the alcohol criterion as well as zero, the qualification of clinical relevance is undecided (C—inconclusive). Figure and description taken with permission from van der Sluiszen et al. (2019)
FIGURE 3
FIGURE 3
Left: Mean (±SE) SDLP for controls and antidepressant user groups. Right: mean (95% CI) differences in SDLP between antidepressant user groups and controls. The dotted line indicates the change in performance after alcohol intake (relative to placebo). Symbols above bars indicate significant difference from controls, p < 0.05. BAC, blood alcohol concentration; LT3−, users treated less than 3 years; LT3+, users treated longer than 3 years; SDLP, standard deviation of lateral position
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