ADHD Medication Helps Teens Drive Safely

How well a teenager with attention-deficit/hyperactivity disorder (ADHD) performs behind the wheel of a car may be directly influenced by optimizing dosing of methylphenidate, especially in the afternoon and evening.

A new, small pilot study finds that the OROS formulation of methylphenidate (Concerta) significantly improves a teen’s ability to operate a vehicle safely and consistently, compared with common three-times-a-day dosing of immediate-release formulations of methylphenidate (MPH).

The patented OROS formulation, developed by Alza Pharmaceuticals and now marketed by McNeil Consumer and Specialty Pharmaceuticals, optimizes blood levels of MPH by allowing a steadily increasing dose of medication to be absorbed throughout the day and into the evening. The amount of OROS-MPH released increases throughout the day to overcome the phenomenon of acute tolerance that develops with multiple doses of MPH.

The study, which appeared in the March Journal of the American Academy of Child and Adolescent Psychiatry, was funded by McNeil.

Leading Cause of Death

“For all teenagers, motor vehicle accidents are the leading cause of death,” noted Daniel J. Cox, Ph.D., a professor of psychiatric medicine and director of the Center for Behavioral Medicine Research at the University of Virginia Health System and principal investigator of the study.

“For adolescents with ADHD, you multiply that by a factor of four, and it becomes a huge problem,” Cox told Psychiatric News.

Cox and his colleagues conducted a randomized, crossover, single-blind study comparing the two formulations’ effects on driving performance in six males aged 16 to 19 with ADHD. Each participant started the study either taking OROS-MPH once a day at 8 a.m. or three-times-a-day dosing of immediate-release MPH.

After seven days of consistent dosing, each participant drove a sophisticated driving simulator at 2 p.m., 5 p.m., 8 p.m., and 11 p.m. The primary outcome was a computer-quantified, impaired-driving score (IDS) generated by the simulator.

The IDS measured multiple variables such as driving speed, veering off road, crossing the center line, standard deviation of steering, inappropriate braking, percent of stop signs or stop lights missed, and whether drivers “bumped” other objects or crashed during their simulated test.

In addition, each driving session was observed by an independent rater who was blind to the medication each subject was taking.

On the day following driving-performance testing, each participant was switched to the opposite medication regimen, maintained for seven days, and then retested (using the same simulator equipment, but not the same simulation). Thus, each subject was effectively his or her own matched control within the two medication regimens tested.

“We wanted to sample driving ability throughout the day and into the evening,” Cox said. “As a parent of an ADHD child, as well as a clinician, it is clear to me that the therapeutic benefits of methylphenidate don’t last a long time, certainly not through the afternoon and into the evening.” But, Cox noted, afternoon and evening timeframes are precisely when teenagers are most likely to be driving.

‘Ritalin Rollercoaster’ Experienced

With immediate-release formulations of MPH that are dosed three times a day, Cox explained, patients experience very high blood levels of MPH in the 60 to 90 minutes immediately following a dose, then very low blood levels after three to five hours. Once they take another dose, the blood level dramatically increases again, only to plummet as that second dose wears off. What you end up with is a phenomenon many call the “Ritalin rollercoaster.”

Long-acting stimulants were developed over the last 10 years in an attempt to eliminate the wide variations over time in MPH blood levels, thus leading to more consistent control of symptoms. Yet the OROS formulation is the only one that offers continuous, sustained release MPH, in an ascending dose curve, compared with other long-acting formulations (such as Novartis’s Ritalin LA) that are simply two doses in one pill, with the doses designed to dissolve at different times.

“At 2 p.m. and 5 p.m., both medications should be at fairly high blood levels, but by 8 p.m. the immediate-release MPH should be pretty low, while the OROS-MPH should just be starting to wear off,” Cox said. “By 11 p.m., there should be virtually no drug left from either dosing regimen.”

What the team found was a surprise, Cox said. Driving performance in subjects taking either MPH or OROS-MPH were good at 2 p.m. and 5 p.m., just as the researchers had hypothesized.

“By 8 p.m., those taking MPH were driving five times worse than they did at 2 p.m.,” Cox said. “What we didn’t anticipate were the continued benefits of the OROS formulation. Even during testing at 11 p.m., performance in the driving simulator was slightly better than at 2 p.m.”

While Cox is quick to note that the study’s small sample size is a limitation, he said that the standard deviations within each medication group were small, and each subject on OROS-MPH performed at least two standard deviations better than those taking immediate-release MPH.

Cox and his team are working on further studies to try to duplicate the findings. The new studies look at a much larger population, with both male and female subjects. The team is also working on comparisons between the different long-acting medications and placebo.In addition, they have a study in press that uses real-world driving rather than simulator driving.

An abstract of “Impact of Methylphenidate Delivery Profiles on Driving Performance of Adolescents With Attention-Deficit/Hyperactivity Disorder: A Pilot Study,” is posted online at www.jaacap.com. Select “Archive” and then the March 2004 issue. ▪