The effects of lisdexamfetamine dimesylate on the driving performance of young adults with ADHD: A randomized, double-blind, placebo-controlled study using a validated driving simulator paradigm

Abstract

Young adults with Attention Deficit Hyperactivity Disorder (ADHD) have been shown to be at increased risk for impairment in driving behaviors. While stimulant medications have proven efficacy in reducing ADHD symptomatology, there is limited knowledge as to their effects on driving impairment. The main aim of this study was to assess the impact of lisdexamfetamine dimesylate (LDX) on driving performance in young adults with ADHD using a validated driving simulation paradigm. This was a randomized, double-blind, 6-week, placebo-controlled, parallel-design study of LDX vs. a placebo on driving performance in a validated driving simulation paradigm. Subjects were sixty-one outpatients of both sexes, 18–26 years of age, who met DSM-IV criteria for ADHD. Subjects were randomized to receive LDX or placebo after a baseline driving simulation and completed a second driving simulation six weeks after beginning drug or placebo. Examination of reaction time across five surprise events at post-treatment showed a significant positive effect of medication status. LDX treatment was also associated with significantly fewer accidents vs. placebo. LDX treatment was associated with significantly faster reaction times and a lower rate of simulated driving collisions than placebo. These results suggest that LDX may reduce driving risks in young adults with ADHD.

Introduction

An emerging literature documents that Attention-Deficit /Hyperactivity Disorder (ADHD) is a significant risk factor for motor vehicle accidents and driving impairment. In several studies, individuals with ADHD, particularly young drivers, reported significantly more traffic citations for speeding and vehicular crashes, as well as more license suspensions than controls (Barkley, 2004; Barkley et al., 2002, 1996; Cox et al., 2000; Fischer et al., 2007; National Highway Traffic Safety Administration (NHTSA) National Center for Statistics and Analysis, 2009; Reimer et al., 2005; Thompson et al., 2007). A recent follow-up study found that in comparison to controls, children with ADHD grown-up had less safe driving habits, more impulsive errors while operating a motor vehicle in natural settings, a greater frequency of license suspensions, and a greater likelihood of various adverse driving outcomes (e.g., reckless driving, hit and run crash, etc.) (Fischer et al., 2007).

While stimulant medications have proven efficacy in reducing ADHD symptomatology (Adler et al., 2008; Biederman et al., 2006; Spencer et al., 2007; Weisler et al., 2006), the extent to which these clinical effects generalize to driving impairment associated with ADHD remains uncertain. Although there have been a number of studies that examined medication effects on driving outcomes in subjects with ADHD (Barkley et al., 2005; Cox et al., 2000, 2006; Cox et al., 2004; Kay et al., 2009), their results are difficult to interpret given limited information on the validity of the driving simulation paradigm used, simulator sickness, statistical power, sensitivity to practice effects, and range of driving conditions (Jerome et al., 2006).

To address the limitations of the existing driving simulation literature in ADHD, our group validated a novel driving simulation paradigm (Reimer et al., 2006) comparing the driving performance of subjects with and without ADHD on a simulation. The simulation included a range of driving environments (rural, highway, urban) and differing stimulus intensity (active, monotonous), in order to vary driving demands in ways observed on actual roadways. In addition, the simulated driving conditions included periods of both single task driving as well as dual task driving (e.g. driving while having a cellular phone conversation). A set of studies involving community samples established good correspondence between patterns of visual attention allocation (Reimer, 2009; Reimer, Mehler, Wang, et al., 2010; Wang et al., 2010) and heart rate (Reimer & Mehler, 2011) observed in this simulator and data collection in the field supporting the ecological validity of this driving simulation paradigm.

A series of recent studies demonstrated that this simulation differentiated ADHD drivers from controls (Biederman et al., 2007; Fried et al., 2009; Reimer et al., 2007; Reimer, Mehler, D'Ambrosio, et al., 2010). Using this simulation, we found that ADHD drivers were more likely to crash into a sudden peripheral surprise event (cyber dog) under monotonous, low stimulus conditions after an extended period of driving (Biederman et al., 2007). In a follow-up of that study (Reimer et al., 2010), young adults with ADHD had lower scores on a phone task, longer pauses at stop signs, and slower acceleration when resuming travel during city driving. Furthermore, when compared to controls, ADHD subjects reported a higher frequency of speeding, passing and weaving in traffic, and number of real life accidents (Reimer et al., 2006), which corresponded with behaviors observed in the simulation. This further supports the validity of our driving simulation paradigm.

The main aim of this study was to assess the impact of treatment for ADHD on driving performance in young adults with ADHD using this validated laboratory driving paradigm. To this end, we conducted a randomized, 6-week, double-blind, placebo-controlled, parallel-design study of the FDA-approved stimulant medicine lisdexamfetamine dimesylate (LDX) to investigate its effect on driving behavior in young adult drivers with ADHD. We hypothesized that treatment with LDX would improve driving behavior in young drivers with ADHD. To the best of our knowledge, this is the first randomized clinical trial examining driving behavior in a driving simulation paradigm that has been shown to have a high degree of correspondence with real world driving across a range of driving behaviors.