Both methylphenidate PRC-063 and lisdexamfetamine led to improved performances for drivers with ADHD.
Daniel J. Cox, PhD, AHPP
While long-acting stimulants can improve the driving safety of adolescents with attention deficit/hyperactivity disorder (ADHD), they could wear off in the evening when severe vehicular collisions are more common.
A team, led by Daniel J. Cox, University of Virginia Health Sciences Center, Department of Psychiatry and Neurobehavioral Sciences, investigated the non-inferiority of 2 long-acting psychostimulants on driving performance in young adults with ADHD.
The investigators examined 44 patients receiving routine care who drove a simulator to assess screening executive function. In the randomized, double-blind, cross-over procedure, each participant was dose-optimized on controlled-release methylphenidate PRC-063 (45, 70, or 100 mg/day) or lisdexamfetamine (30, 50, or 70 mg/day).
The mean age of the patient population was 24.5 ±4.50 years old, while 47% of the patients were female.
After dose optimization, each patient was assessed in the simulator at 1, 9, 12, and 15 hours post-dose. Each patient then repeated the titration and simulator assessments with the other medication.
The investigators sought primary outcomes of the Tactical Driving Quotient (TDQ non-inferiority margin = 7.5), which measured overall driving skill.
The investigators found the TDQ mean and standard error was 99.9±1.84 for the PRC-063 group and 100.1±1.84 for the lisdexamfetamine group, while the least squares mean difference was 0.3±1.08 (95% CI, -2.4 to 1.8; P = 0.793). This shows non-inferiority of PRC-063 and lisdexamfetamine.
In addition, the time course of the TDQ response was flat for both treatment types and compared to normative driving performance data from the Department of Motor Vehicle (mean TDQ, 100±15), patients scored 105 and 104.5 for PRC-063 and lisdexamfetamine, respectively.
Executive function composite scores increased from 0.88 at screening to 1.99 and 2.05 with PRC-063 and lisdexamfetamine, respectively (P < 0.01; post-hoc).
The investigators also found that 73% of the participants experienced a treatment-emergent adverse event related to either study drug, with the most common adverse as expected for the medication class and subject population.
“Once-daily [PRC-063] or [lisdexamfetamine] had comparable effects on the driving performance of young adults with ADHD,” the authors wrote. “Both stimulants led to performance that exceeded the average DMV driver, improved [executive function] over routine care, and resulted in similar driving responses at 1, 9, 12 and 15 hours post-dose.”
Vehicular collisions are a leading cause of adolescent morbidity and mortality, with the accident rate three-times higher in adolescents with ADHD when compared to neuro-typical peers.
In 2017, a team of investigators conducted a meta-analysis of 34 randomized controlled trials to compare the safety and efficacy of different leading ADHD medications.
The results showed that ADHD symptoms improved more with lisdexamfetamine than with several other ADHD medications, while methylphenidate immediate release was judged the best tolerated.
The average daily dose of lisdexamfetamine ranged from 44.4 to 51.52 mg, while the average daily dose for methylphenidate extended release 18 to 39.03mg and 17.35 to 30.76 mg for methylphenidate.
The study, “PRC-063 and Lisdexamfetamine ADHD Medications Similarly Improve Driving Simulator-Based Executive Function and Normalize Tactical Driving Performance,” was published online by NEI.