Atomoxetine: The First Nonstimulant for the Management of Attention-Deficit/Hyperactivity Disorder

Shelby L. Corman; Bethany A. Fedutes; Colleen M. Culley

Disclosures

Am J Health Syst Pharm. 2004;61(22) 

In This Article

Abstract and Introduction

Purpose: The pharmacology, pharmacokinetics, clinical efficacy, safety, drug interactions, dosage and administration, and place in therapy of atomoxetine in the treatment of attention-deficit/hyperactivity disorder (ADHD) are reviewed.
Summary: Atomoxetine is a methylphenoxy-benzenepropanamine derivative with antidepressant activity and is thought to enhance noradrenergic function via selective inhibition of the presynaptic norepinephrine transporter. Atomoxetine is rapidly absorbed from the gastrointestinal tract, reaching peak levels in 1.83 hours in pediatric patients and 1-1.5 hours in adults. The clinical efficacy of atomoxetine in the treatment of ADHD has been evaluated in six published clinical trials of children and adolescents and two studies enrolling only adults. Clinical trial data indicate that atomoxetine is safe and well tolerated for the treatment of ADHD; however, safety data about long-term use (greater than one year) are unavailable. Adverse events reported in clinical trials were mainly mild to moderate and transient in nature. Recommended dosing of atomoxetine is weight based, and dosages should be adjusted to a target dosage of 1.2 mg/kg/day in children and adolescents weighing 70 kg or less and to 80 mg/day in children and adolescents weighing over 70 kg and adults. While current guidelines from the American Academy of Pediatrics recommend stimulants and behavior modification as first-line therapy for the management of ADHD, atomoxetine offers those patients who do not respond to or cannot tolerate one or more stimulants an alternative treatment option.
Conclusion: Atomoxetine, the first non-stimulant approved for the management of ADHD in children, adolescents, and adults, provides patients who have not responded to or cannot tolerate one or more stimulants an alternative treatment option.

Attention-deficit/hyperactivity disorder (ADHD) affects an estimated 4-12% of school-aged children in the United States.[1] ADHD is diagnosed by the presence, in two or more settings, of at least 6 of 18 characteristics indicating hyperactivity, impulsivity, and inattention.[2] In addition, these characteristics must be evident by age seven, persist for at least six months, and significantly impair academic, social, or occupational function. Up to 65% of children with ADHD also have co-morbid psychiatric disorders, including mood disorders, depression, anxiety, and oppositional defiant disorder.[3] Functional problems, such as academic underachievement and difficulty with social and family interactions, are also likely in these patients. Persistence of ADHD into adulthood has been reported in 4-60% of patients, and adults with ADHD are more likely to exhibit occupational, financial, and social deficiencies.[4,5,6]

ADHD is caused by a deficit in response inhibition, an executive function in the prefrontal cortex. As a result, those with this disorder are unable to control responses to external stimuli. Patients with ADHD also display a dysregulation of arousal wherein they are inappropriately stimulated during exciting activities and inattentive in the completion of more routine tasks. This condition may be attributed to dysregulation of norepinephrine, as noradrenergic activation is associated with the attention span.[7]

Medications that balance the dysregulation of dopamine and norepinephrine improve response inhibition and regulate arousal, leading to improved performance, which supports the hypothesis that modification of monoamine transmission in critical brain areas may be the basis for pharmacotherapy of ADHD.[7] Historically, only stimulants have been approved for use in children to treat ADHD. Noradrenergic agents, such as tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), bupropion, and clonidine, have been used in ADHD therapy. While these agents have shown efficacy, there are potential limitations to their use, including an approximately 30% failure rate, intolerance, adverse effects including potential worsening of comorbid anxiety, dosage regimens typically consisting of multiple doses of short- or long-acting agents throughout the day, and concerns about potential abuse.[8,9]

Atomoxetine hydrochloride (Strattera, Eli Lilly, Indianapolis, IN), a selective norepinephrine-reuptake inhibitor, is the first nonstimulant indicated for the management of ADHD in children over six years of age, adolescents, and adults.[10] This article reviews the pharmacology, pharmacokinetics, clinical efficacy, safety, drug interactions, dosage and administration, and place in therapy of atomoxetine in the treatment of ADHD.

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