What is the recommended treatment and dosage of Atomoxetine (Strattera) for Attention Deficit Hyperactivity Disorder (ADHD)?

Atomoxetine for ADHD: Treatment Recommendations and Dosing

Treatment Positioning

Atomoxetine is FDA-approved as a selective norepinephrine reuptake inhibitor for ADHD treatment in children, adolescents, and adults, but should be considered second-line therapy after stimulants due to smaller effect sizes and delayed onset of action. 1, 2

• Stimulants remain first-line therapy for ADHD due to larger effect sizes compared to non-stimulants 1
• Atomoxetine is specifically indicated as first-line in patients with comorbid substance use disorders, tic disorders, or Tourette's syndrome 1
• It provides "around-the-clock" symptom control without the peaks and valleys of stimulant medications 1
• Atomoxetine carries negligible risk of abuse or diversion and is not a controlled substance 3, 4

Dosing and Administration

Children and Adolescents (up to 70 kg)

• Starting dose: 0.5 mg/kg/day 1, 2
• Target dose: 1.2 mg/kg/day 1, 2
• Maximum dose: 1.4 mg/kg/day 1, 2
• Titrate every 7-14 days based on clinical response 1

Children and Adolescents (over 70 kg) and Adults

• Starting dose: 40 mg/day 1, 2
• Target dose: 80 mg/day 1, 2
• Maximum dose: 100 mg/day 1, 2
• Titrate every 7-14 days based on clinical response 1

Administration Options

• Can be given as a single daily dose (morning or evening) or split into two evenly divided doses 1, 2
• Split dosing may reduce side effects initially, with option to transition to once-daily dosing later 1
• Once-daily morning dosing has been proven effective in clinical trials 2

Critical Safety Monitoring

Black Box Warning

• FDA Black Box Warning for increased risk of suicidal ideation in children and adolescents 1, 2
• Monitor closely, especially during the first few months of treatment or with dose changes 1
• No suicides occurred in clinical trials 2

Cardiovascular Monitoring

• Monitor blood pressure and heart rate at baseline and regularly during treatment 1, 2
• Sudden death, stroke, and myocardial infarction have been reported in association with atomoxetine 2
• Should not be used in patients with serious structural cardiac abnormalities, cardiomyopathy, or serious heart rhythm abnormalities 2
• Use with caution in patients with hypertension, tachycardia, or cardiovascular/cerebrovascular disease 2

Hepatic Monitoring

• Discontinue atomoxetine and do not restart in patients with jaundice or laboratory evidence of liver injury 2

Psychiatric Monitoring

• Screen for bipolar disorder prior to starting atomoxetine 1, 2
• Monitor for emergence of new psychotic or manic symptoms 2
• Monitor for appearance or worsening of aggressive behavior or hostility 1, 2

Common Adverse Effects

Most common side effects include: 1, 2

• Decreased appetite (very common)
• Nausea and vomiting
• Headache
• Somnolence (particularly initially)
• Abdominal pain
• Fatigue
• Dizziness
• Dry mouth (in adults) 3, 4
• Insomnia (in adults) 3, 4
• Sexual problems (in adults) 3, 4

Urinary effects: 2

• Urinary hesitancy and retention may occur
• Priapism requires prompt medical attention 2

Efficacy Timeline and Follow-Up

• Full therapeutic effects take 6-12 weeks to develop 1
• Assess response after 6-12 weeks of treatment 1
• In clinical trials, atomoxetine at 1.2 mg/kg/day showed superior outcomes compared to placebo, with no additional benefit at 1.8 mg/kg/day 2, 5
• The 0.5 mg/kg/day dose was not superior to placebo 2, 5

Special Populations

CYP2D6 Considerations

• Dose adjustments necessary for CYP2D6 poor metabolizers or when used with strong CYP2D6 inhibitors 1, 2
• Atomoxetine is metabolized through CYP2D6 1

Hepatic Impairment

• Dose adjustment required in hepatic impairment 2

Pediatric Growth Monitoring

• Height and weight should be monitored in pediatric patients 2
• Atomoxetine shows fewer effects on appetite and growth compared to stimulants 1

Alternative Treatment Options

If atomoxetine is ineffective or poorly tolerated after 6-12 weeks: 1

• Consider trial of stimulant medication (methylphenidate or amphetamine derivatives)
• Consider alpha-2 adrenergic agonists (extended-release guanfacine or clonidine)
• Alpha-2 agonists are specifically approved for sleep disturbances comorbid with ADHD 1

Special Clinical Scenarios

Autism Spectrum Disorder with ADHD

• Atomoxetine has demonstrated efficacy in patients with comorbid ASD and ADHD 1, 6
• In younger children (3-6 years) with comorbid ADHD and ASD, atomoxetine at 1.2-1.8 mg/kg/day appeared well tolerated, though close monitoring remains essential 6

Sleep Disturbances

• Atomoxetine is preferred over stimulants when sleep disturbances are problematic 1
• Can be administered in the evening if needed 1
• Provides continuous 24-hour coverage without stimulant-related sleep disruption 1