Rebound Effects with Long-Acting Amphetamine or Methylphenidate Stimulant Medication Preparations among Adolescent Male Drivers with Attention-Deficit/Hyperactivity Disorder

Abstract

This study investigated whether OROS methylphenidate (OROS MPH, Concerta) or extended-release mixed amphetamine salts (se-AMPH ER, Adderall XR) were associated with worsening of driving performance, or drug rebound, relative to placebo 16-17 hours post-ingestion. Nineteen male adolescent drivers aged 17-19 with attention-deficit/hyperactivity disorder (ADHD) were compared on a virtual reality driving simulator and an on-road drive after taking 72 mg of OROS MPH, 30 mg of se-AMPH ER, or placebo. Medication was taken at 08:00 in a randomized, double-blind, placebo-controlled, crossover study. Participants drove a simulator at 17:00, 20:00, 23:00, and 01:00, and drove their own cars over a 16-mile road course at 24:00. The main outcome measures were composite scores of driving performance. Neither OROS MPH nor se-AMPH ER was associated with significant worsening of simulator performance relative to placebo 17 hours post-ingestion in group comparisons. However, inattentive on-road driving errors were significantly more common on se-AMPH ER relative to placebo at midnight (p = 0.04), suggesting possible rebound. During both late simulator and on-road testing, driving performance variance was approximately 300% greater during the se-AMPH ER compared to the OROS MPH condition.

Adult Attention-Deficit/Hyperactivity Disorder and Driving: Why and How to Manage It

“…These improvements are likely attributable in part to improvements in symptoms of ADHD, particularly inattentive symptoms. Although one previous study demonstrated that extended-release mixed amphetamine salts at a dose of 30 mg did not improve the driving performance of adolescents [31], and at 16 h postingestion, it was associated with medication rebound [27], a more recent study demonstrated that this medication improved daytime simulator driving performance of adults at a dose of 50 mg [26].…”

“…They found that amphetamine, but not atomoxetine, significantly improved performance on the driving simulator, as determined by the overall Driving Safety Score (composed of seven simulatorderived variables and self-reported response of number of crash-likely events) and reduced ADHD symptoms. However, Cox et al [27] reported that during on-road testing, long-acting mixed amphetamine salts were associated with more inattentive driving errors (eg, taking eyes off the road, running stop signs, crossing median line) 16 h after dosing compared with placebo, suggesting possible drug rebound effects, whereas the long-acting methylphenidate formulation (Concerta, Ortho-McNeil-Janssen, Titusville, NJ) was not associated with any decay in driving performance 16 h after dosing.…”

Autorijden met ADHD

“…Positieve effecten op het rijgedrag van personen met ADHD zijn ook gerapporteerd voor stimulantia anders dan methylfenidaat, zoals langwerkende gemengde amfetaminezouten en lisdexamfetamine dimesylaat. Echter, ondanks de positieve effecten van langwerkende gemengde amfetaminezouten bestaat er ook enig bewijs dat 16-17 uur na inname het aantal fouten op de weg door onoplettendheid toeneemt, wat op mogelijke reboundeffecten zou kunnen wijzen [81]. Daarnaast is aangetoond dat ook niet-stimulantia (atomoxetine), die eveneens worden gebruikt voor de behandeling van ADHD, de rijvaardigheid van personen met ADHD kunnen verbeteren.…”

Safety of stimulant treatment in attention deficit hyperactivity disorder: part II

“…Yet, there has been minimal research documenting such phenomena [139,140]. There is a case report of withdrawal hyperactivity and psychosis after suddenly stopping MPH due to concerns about depression and suicidal behavior in an 8-year-old boy after 3 years of treatment.…”