Effects of Atomoxetine generic and Methylphenidate on Sleep in Children with Attention-Deficit/ Hyperactivity Disorder

Author: R. Bart Sangal MD, Clinical Neurophysiology Services PC, Troy, Michigan

Presenter: Virginia Sutton, PhD, Lilly Research Laboratories, Indianapolis, Indiana

Attention-deficit/hyperactivity disorder (ADHD) affects approximately 3% to 7% of school-aged children. It is characterized by inattention and/or hyperactivity and impulsivity. The disorder is thought to be caused by a dysregulation of nore-pinephrine and dopamine in the prefrontal cortex and associated brain structures.

Therapy for ADHD, which has traditionally relied on the administration of stimulants, does not produce an adequate response or is not tolerated in 30% or more of patients. In a 1999 survey, 61% of children with ADHD who took stimulant medications experienced insomnia at least one night per week, compared with 32% of children with ADHD who did not take stimulants.

Atomoxetine (ATX) (Strattera drug, Eli Lilly) is a highly specific, presynaptic inhibitor of the norepinephrine transporter. It is indicated for ADHD in children, adolescents, and adults.

In a randomized, double-blind, crossover trial of 85 children with ADHD, as defined in the Diagnostic and Statistical Manual, fourth revised edition (DSM-IV), investigators compared ATX twice daily with methylphenidate (MPH) three times daily to determine whether ATX, because it is not a stimulant, interferes with sleep less than MPH does. The children ranged in age from six to 14 years, and 24.7% were girls.

Two treatment periods of 6.7 weeks were separated by a 10- to 20-day drug-free interval. Actigraphy (a wrist monitor), polysomnography (at two sites), and diaries kept by parents and children were used to assess the outcomes. Subjects agreed to refrain from consuming caffeinated beverages and to maintain a consistent “lights out” bedtime; the participants were excluded for less than 85% adherence.

The mean final doses were 1.56 mg/kg per day for ATX and 1.12 mg/kg per day for MPH. In relation to the baseline values, there was a significant (P < .001) increase in the time to sleep onset with MPH (3.4 minutes), compared with ATX (30.1 minutes). As evaluated by actigraphy, the actual total sleep time favored ATX.
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For 39 patients who were assessed via polysomnography, the time to the first sleep episode was significantly less with ATX (-0.3 minutes vs. 16.8 minutes, both from baseline; P < .001). The same pattern from baseline was revealed in the time to the first persistent sleep (-0.2 minutes vs. 16.8 minutes), but the number of awakenings favored MPH (-4.4 vs. -6.7; P = .002).

In the children’s diaries, responses to questions (time to falling asleep, difficulty getting up, how well did you sleep? how sleepy do you feel today?) all favored ATX, significantly for the first three items.

Parent diary results favored ATX for difficulty in getting the child out of bed, difficulty with getting the child ready for bed, arguing or struggling in the morning, irritability in the morning, difficulty in getting ready for bed, and difficulty with falling asleep. MPH was not favored in any category. Both ATX and MPH were well tolerated in this patient population.

Overall, patients taking ATX experienced a shorter time to the onset of sleep, compared with MPH, as measured by actig-raphy and polysomnography. Patients taking MPH had less actual sleep time, as assessed by actigraphy, and more sleep-related problems, according to both child and parent diaries. online pharmacy prescription drugs

A limitation of this study was that polysomnography was performed in only a subset of patients.