Sex differences in effectiveness of extended-release stimulant medication among adolescents with attention-deficit/hyperactivity disorder.

This study examined whether adolescent females with attention-deficit/hyperactivity disorder (ADHD) are differentially responsive than their male counterparts to extended-release stimulant medications. This investigation may bear special importance for an adolescent (as opposed to child) population, because hormonal and metabolism differences between sexes are most likely to emerge at this time. Male (n = 19) and female (n = 16) adolescents, ages 16-19 with ADHD, participated in a randomized, double-blind crossover study evaluating the effectiveness of osmotic-release methylphenidate, extended release amphetamine salts, placebo, and routine limited medication regimen. Medication efficacy was evaluated using ADHD symptom ratings from adolescent self-report and parent report, along with objective measures of inattention and hyperactivity/impulsivity during driving performance and neuropsychological tasks. Males and females were largely equivalent in impairment, and medication was similarly effective in reducing symptoms. No interactions were found between sex and medication on any measure of effectiveness or side effects. This finding suggests that the efficacy and tolerability of extended-release stimulant medications is equivalent for male and female adolescents with ADHD.

Rebound effects with long-acting amphetamine or methylphenidate stimulant medication preparations among adolescent male drivers with attention-deficit/hyperactivity disorder.

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.

Manual transmission enhances attention and driving performance of ADHD adolescent males: pilot study.

OBJECTIVE: Inattention is a major contributor to driving mishaps and is especially problematic among adolescent drivers with ADHD, possibly contributing to their 2 to 4 times higher incidence of collisions. Manual transmission has been demonstrated to be associated with greater arousal. This study tests the hypotheses that manual transmission, compared to automatic transmission, would be associated with better attention and performance on a driving simulator. METHOD: Ten adolescent drivers with ADHD practice driving on the simulator in the manual and automatic mode. Employing a single-blind, cross-over design, participants drive the simulator at 19:30 and 22:30 hr for 30 min in both transmissions and rate their attention to driving. RESULTS: Subjectively, participants report being more attentive while driving in manual transmission mode. Objectively, participants drive safer in the manual transmission mode. CONCLUSION: Although in need of replication, this pilot study suggests a behavioral intervention to improve driving performance among ADHD adolescents.

Effect of extended release stimulant-based medications on neuropsychological functioning among adolescents with Attention-Deficit/Hyperactivity Disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with diminished neuropsychological functioning. This randomized, double-blind, placebo controlled, study is the first comparison of two extended release stimulant-based medications (Adderall XR and Concerta) and placebo on ADHD neuropsychological functioning. Adolescents diagnosed with ADHD (n=35, 19 males) completed three separate assessments (5, 8, 11 p.m.) on three different days and medications (Concerta, Adderall XR and Placebo). The assessments consisted of two different neuropsychological tests, the Delayed Matching-to-Sample and the Go/No-go (GNG), which measure visual memory, attention span, and response inhibition. Results indicated a significant effect of medication on signs of impulsivity and memory. Simple contrasts showed significant improvement in neuropsychological functioning (as measured by commission errors, reaction time, and recall accuracy) when participants were taking Concerta as opposed to placebo. These results suggest that Concerta impacts not only symptomatic behaviors but also cognitive functioning, which has implications for both academic performance and daily functioning.

Relative benefits of stimulant therapy with OROS methylphenidate versus mixed amphetamine salts extended release in improving the driving performance of adolescent drivers with attention-deficit/hyperactivity disorder.

OBJECTIVE: Automobile accidents are the leading cause of death among adolescents, and collisions are 2 to 4 times more likely to occur among adolescents with attention-deficit/hyperactivity disorder. Studies have demonstrated that stimulants improve driving performance. This study compared 2 long-acting stimulant medications during daytime and evening driving evaluations. METHODS: Adolescent drivers with attention-deficit/hyperactivity disorder were compared on a driving simulator after taking 72 mg of OROS methylphenidate, 30 mg of mixed amphetamine salts extended release, or placebo in a randomized, double-blind, placebo-controlled, crossover study design. During laboratory testing, adolescents drove a driving simulator at 5:00 pm, 8:00 pm, and 11:00 pm. Driving performance was rated by adolescents and investigators. RESULTS: The study included 35 adolescent drivers with attention-deficit/hyperactivity disorder (19 boys/16 girls). The mean age was 17.8 years. The overall Impaired Driving Score demonstrated that OROS methylphenidate led to better driving performance compared with placebo and mixed amphetamine salts extended release, whereas mixed amphetamine salts extended release demonstrated no statistical improvement over placebo. Specifically, relative to placebo, OROS methylphenidate resulted in less time driving off the road, fewer instances of speeding, less erratic speed control, more time executing left turns, and less inappropriate use of brakes. OROS methylphenidate and mixed amphetamine salts extended release worked equally well for male and female adolescents and equally as well with teenagers who have combined and inattentive subtypes of attention-deficit/hyperactivity disorder. CONCLUSIONS: This study validates the use of stimulants to improve driving performance in adolescents with attention-deficit/hyperactivity disorder. In the study, OROS methylphenidate promoted significantly improved driving performance compared with placebo and mixed amphetamine salts extended release.

Controlled-release methylphenidate improves attention during on-road driving by adolescents with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with a 3- to 4-fold increase in both driving-related accidents and associated injuries. Methylphenidate (MPH) is the most commonly prescribed psychostimulant medication for ADHD. It has been demonstrated to improve performance on a driving simulator. This study investigated whether a once-daily, long-acting, osmotic, controlled-release MPH formulation improves the driving performance of ADHD adolescents while driving their own car on an actual road segment. METHODS: Twelve ADHD-diagnosed male adolescent drivers (mean age, 17.8 years) prescribed a standard dose of 1.0 mg/kg (if they were not already taking methylphenidate) of controlled-release MPH participated in this repeated-measures crossover study. On 2 separate occasions (off/on medication randomized), participants drove a standard 16-mile road course incorporating rural, highway, and urban streets. A rater, blind to medication conditions, sat in the back seat and rated impulsive (eg, "cutting off" another driver) and inattentive (eg, drove past designated turn) driving errors. RESULTS: Impulsive driving errors were observed to occur rarely under both medication and no medication conditions. Inattentive driving errors were more common and were significantly reduced while the subject was on medication (4.6 versus 7.8; P <.01). The improvement in driving performance (change in number of errors recorded) from first to second testing was positively correlated with medication dosage (r = 0.60; P <.01). CONCLUSIONS: Once-daily controlled-release MPH improves real-life driving performance of adolescent males diagnosed with ADHD. In particular, it significantly reduces driving errors arising from inattention.

Impact of methylphenidate delivery profiles on driving performance of adolescents with attention-deficit/hyperactivity disorder: a pilot study.

OBJECTIVE: Adolescents with attention-deficit/hyperactivity disorder (ADHD) are at high risk for driving accidents. One dose of methylphenidate (MPH) improves simulator driving performances of ADHD-diagnosed adolescents at 1.5 hours post-dose. However, little is known about the effects of different MPH delivery profiles on driving performance throughout the day. METHOD: This randomized, crossover, single-blind study compared osmotic, controlled-release oral system (OROS) MPH (Concerta) given q.d. to immediate-release MPH (Ritalin) given in equal doses t.i.d. on driving performance among six male ADHD-diagnosed adolescent drivers aged 16 to 19 years. Under each treatment condition, participants were maintained on their medication dosage for 7 days, then drove a sophisticated driving simulator at 2 p.m., 5 p.m., 8 p.m., and 11 p.m. The primary outcome measure was each participant's computer-quantified Impaired Driving Score (IDS). RESULTS: IDS worsened in the evenings for participants receiving MPH t.i.d. but remained stable when they received once-daily OROS MPH. Participants performed significantly better when receiving OROS MPH q.d. compared with MPH t.i.d. (F = 9.3, df = 1, p =.004). When MPH was given t.i.d., IDS significantly worsened beginning at 8 p.m. compared to OROS MPH (p =.01). CONCLUSIONS: Participants demonstrated significantly less variability and better driving performance when receiving OROS MPH q.d. compared to MPH t.i.d., particularly in the evenings.