PHILADELPHIA – Children who had attention-deficit hyperactivity disorder had a shorter time to sleep onset and more actual sleep time when they were treated with atomoxetine than with methylphenidate, according to a study comparing the two ADHD treatments that was presented at the annual meeting of the Associated Professional Sleep Societies.
Children were able to get to sleep more quickly and slept longer during a drug-free baseline period.
Methylphenidate caused fewer awakenings and produced less awake time during the night than did atomoxetine.
“The results of the study may not be a big surprise to clinicians familiar with these drugs, as methylphenidate is a stimulant and atomoxetine is not.
“However, the half-life of methylphenidate is so short that, by bedtime, it is gone. So there is some question about its effects,” said Bart Sangal, M.D., director of the Sleep Disorders Institute, Troy, Mich.
The current study was a randomized, double-blind, crossover trial of 85 children with ADHD. The average age of the children was 10.1 years. After a treatment-free baseline period of up to 12 days, patients underwent treatment for up to 7 weeks on one drug. After another drug-free period (10–20 days), patients in the study then crossed over to the other drug for treatment up to 7 weeks.
When compared with the initial treatment-free baseline period, ADHD children who were treated with atomoxetine fell asleep within 12.1 minutes of their baseline, compared with 39.2 minutes for the methylphenidate group. Researchers measured the time to sleep onset by actigraphy, which is a monitor worn like a watch on the wrist at home by the child.
“Both atomoxetine and methylphenidate caused an increase in time to fall asleep, but it was significantly more so with methylphenidate,” Dr. Sangal said.
Actual sleep time also was negatively affected by both drugs. Children who were on atomoxetine slept 15.3 minutes less than at baseline and children who were on methylphenidate slept 29.6 minutes less than at baseline. The difference in sleep times was statistically significant, Dr. Sangal said.
On a positive note, the numbers of wake bouts or awakenings experienced by the participants were decreased, compared with baseline, by the two drugs. But that decrease was more significant with methylphenidate, according to Dr. Sangal.
Children who were on atomoxetine had 1.3 fewer awakenings than at baseline and children on methylphenidate had 4.4 fewer awakenings.
The total awake time was significantly decreased from baseline by 6.3 minutes with methylphenidate, while atomoxetine decreased awake time by only 0.3 minutes, Dr. Sangal said.
“It is possible that the subjects in the study had a worse sleep initiation with methylphenidate and then a compensatory improvement in sleep maintenance,” he said.
The mean final dosages were 1.56 mg/kg per day for atomoxetine and 1.12 mg/kg per day for methylphenidate. Dosage was based on weight and started at 0.5 mg /kg per day for atomoxetine and 0.45 mg/kg per day for methylphenidate. Each subject was titrated upwards to a maximum of 1.8 mg/kg per day for each drug.
There were 21 (25%) female and 64 (75%) male subjects. The ADHD subtypes were: 2 (2%) hyperactive/impulsive; 25 (29%) inattentive; and 57 (68%) combined. In terms of race, 21 (25%) of the participants were of African descent; 62 (73%) were of European descent; and 2 (2%) were categorized as other. Thirty-seven (43.5%) of the participants had previous stimulant exposure and 48 (56.5%) did not.
Only a subset of patients in the study underwent polysomnography in a sleep lab, which Dr. Sangal said was a “limitation of the study.” With polysomnography, atomoxetine compared favorably again with methylphenidate with regard to time to persistent sleep, a polysomnography measure that is akin to sleep onset.
ADHD children treated with atomoxetine fell asleep 0.2 minutes ahead of their baseline, compared with 16.8 minutes after their baseline for the methylphenidate group; the difference was statistically significant. Both atomoxetine and methylphenidate were well-tolerated, he said.
Dr. Sangal is a paid consultant to Lilly Pharmaceuticals. Lilly Pharmaceuticals sponsored the study and manufactures atomoxetine.