Effectiveness of Atomoxetine for ADHD

Abstract

Source: Kelsey DK, Sumner CR, Casat CD, et al. Once-daily atomoxetine treatment for children with attention-deficit/hyperactivity disorder, including an assessment of evening and morning behavior: a double-blind, placebo-controlled trial. Pediatrics. 2004;114:e1–e8.A randomized, double-blind, placebo-controlled trial of atomoxetine was conducted at 12 outpatient centers in the United States, organized and funded by the manufacturer, Lilly Research Laboratories, Indianapolis, Ind. Subjects were 197 children, 6 to 12 years of age (71% male), diagnosed with attention-deficit/hyperactivity disorder (ADHD) (combined subtype in 69% and comorbid oppositional defiant disorder in 35%). Patients received atomoxetine (n=133) (final dose 1.3 ± 0.3 mg/kg; mean 44.5 mg per day; range 10–80 mg per day) or placebo (n=64) once daily in the morning for 8 weeks. ADHD symptoms were assessed throughout the day, including evening and early morning, using the Attention-Deficit/Hyperactivity Disorder Rating Scales-IV-Parent Version: Investigator-Administered and Scored (ADHD RS). An electronic data system was used to record the daily parent assessments of the home behavior of the children in the evening and early morning, including getting up, completing homework, and sitting through dinner.Mean reductions in the total scores of ADHD RS were significantly greater for the atomoxetine-treated patients than the placebo-treated patients, and the benefits were noted on day 1, at the first visit after initiating treatment, and at all subsequent visits. Both inattentive and hyperactive/impulsive symptoms were significantly reduced by atomoxetine, and core symptoms continued to decrease throughout the 8-week study. Efficacy outcomes as determined by the Daily Parent Ratings of Evening and Morning Behavior-Revised (DPREMB-R) were significantly superior for atomoxetine when compared to placebo, in both the evening and morning hours (P<.05). Decreased appetite in 18%, somnolence in 15%, and fatigue in 10% were significantly more frequent with atomoxetine than with placebo (P<.05). Vomiting occurred in 6.1% with atomoxetine and in 1.6% with placebo. Six atomoxetine-treated patients (4.5%) discontinued treatment because of adverse events (somnolence in 3, aggression 1, fatigue 1, and syncope 1), and 1 placebo-treated patient (1.6%) withdrew because of nausea. Eighty percent of atomoxetine-treated patients completed the study, compared to 73% of those receiving placebo.This study confirms previous reports1 showing superior efficacy of once-daily atomoxetine (Strattera) versus placebo in children with ADHD. It demonstrated a lasting effectiveness, not only into the evening but also the next morning, after a single morning dose. An effect was also measured on the first day of treatment. The study did not address school behavior, but teacher-rating scales completed in previous trials have shown significant benefits from atomoxetine in the school environment.1 Short-term studies point to some initial adverse events (decreased appetite, abdominal pain, drowsiness, and fatigue), but none of them life-threatening, and few resulting in discontinuance of therapy. In 1 long-term study,2 adverse events, including slight increases in blood pressure and heart rate, declined in frequency with continued therapy.With any new therapy for a chronic condition such as ADHD, caution about premature usage is advised, especially when alternative drugs with proven effectiveness and safety are available. Atomoxetine appears to have properties not shared by conventional treatments, however, and some specific indications may be proposed: 1) since atomoxetine is not considered a stimulant, it may be recommended as first-line therapy for ADHD in patients who present with comorbid tics, seizure susceptibility, and/or sleep disorders; 2) patients who fail to respond or develop persistent adverse events with stimulant therapy (methylphenidate, amphetamines) may be considered for atomoxetine treatment; and 3) those who have the hyperactive/impulsive subtype or combined type of ADHD, with abnormal behaviors that persist in the evening and early morning hours, may benefit more from the extended efficacy of atomoxetine compared to shorter-acting stimulants. Notwithstanding the encouraging early reports of efficacy and safety of atomoxetine, it is a relatively new addition to the ADHD treatment regimen. Possible long-term adverse effects such as growth delay have not been excluded. Since methylphenidate and amphetamines have been used successfully and without serious side effects for more than 40 years, it seems prudent to rely, when possible, on well-tried and proven remedies as first-line therapy.3This study did not compare atomoxetine to other stimulant drugs used to treat ADHD, so the strength of the effect shown can only be limited to a placebo comparison. However, the study still warrants our attention because it did show improvement in morning and evening behavior compared to placebo use with relatively benign side effects during the study period. Whether long-term use of this drug results in more serious side effects, including poor weight and height growth, awaits further study.