What are the guidelines for prescribing atomoxetine (Strattera) to patients with Attention Deficit Hyperactivity Disorder (ADHD)?

Atomoxetine (Strattera) Prescribing Guidelines for ADHD

Atomoxetine is an effective second-line medication for ADHD treatment, with a medium effect size (0.7) compared to stimulants (1.0), and should be considered primarily when stimulants are contraindicated, ineffective, or not preferred by the patient. 1

Mechanism of Action and Pharmacology

Atomoxetine is a selective norepinephrine reuptake inhibitor (not a stimulant) that works by:

• Binding to norepinephrine transporters, inhibiting presynaptic norepinephrine reuptake 2
• Increasing both norepinephrine and dopamine in the prefrontal cortex 2
• Metabolized primarily through the CYP2D6 pathway 2

Dosing Guidelines

Children and Adolescents

• Starting dose: 0.5 mg/kg/day 1, 3
• Target dose: 1.2 mg/kg/day 1, 3
• Maximum dose: 1.4 mg/kg/day or 100 mg/day (whichever is lower) 2, 3
• Titration: Dose is usually adjusted every 7-14 days 2

Adults

• Starting dose: 40 mg daily 3
• Target dose: 80 mg daily 3
• Maximum dose: 100 mg daily 3

Administration Options

• Can be administered as a single daily dose or split into two evenly divided doses 2
• Evening-only dosing is possible to reduce adverse effects 2
• Takes 6-12 weeks to reach full therapeutic effect (unlike stimulants which work immediately) 2

Clinical Efficacy

• Effective for reducing core ADHD symptoms with medium effect size (0.7) compared to stimulants (1.0) 1
• Less effective than extended-release methylphenidate and mixed amphetamine salts 4
• Provides "around-the-clock" symptom control rather than time-limited effects 2
• Demonstrated efficacy in both short-term and long-term treatment 4

Indications for Preferential Use

Atomoxetine should be considered as first-line instead of stimulants in patients with:

• Substance use disorders or risk of stimulant abuse 2
• Active substance use (requires subspecialist consultation) 2
• Comorbid anxiety disorders or tics 4
• Patients who need 24-hour symptom control 2
• Patients who prefer a non-controlled substance 5

Monitoring Requirements

Before Starting Treatment

• Screen for bipolar disorder 3
• Assess for cardiovascular disease or abnormalities 3
• Obtain baseline vital signs (BP, HR) 3

During Treatment

• First few months: Monitor closely for suicidality, clinical worsening, and unusual changes in behavior 2, 3
• Regular monitoring of:
  • Blood pressure and heart rate 3
  • Growth parameters in children 3
  • Liver function 1
  • Emergence of aggression, hostility, or psychotic/manic symptoms 3

Safety Considerations

Black Box Warning

• Increased risk of suicidal ideation in children and adolescents 3
• No completed suicides occurred in clinical trials 3

Common Adverse Effects

• Children: Dyspepsia, nausea, vomiting, decreased appetite, weight loss 6
• Adults: Dry mouth, insomnia, nausea, decreased appetite, constipation, urinary difficulties, sexual dysfunction (2%), dizziness 6, 5

Serious Adverse Effects (Rare)

• Severe liver injury (discontinue if jaundice or laboratory evidence of liver injury) 3
• Cardiovascular effects: Increased BP and HR 3
• Urinary hesitancy and retention 3
• Priapism (requires prompt medical attention) 3

Drug Interactions

• SSRIs that inhibit CYP2D6 (e.g., paroxetine) can elevate atomoxetine levels 2
• Contraindicated within 2 weeks of MAOI use 3
• Dose adjustment needed for:
  • Patients with hepatic impairment 3
  • Poor CYP2D6 metabolizers (7% of population) 2
  • Concurrent use of strong CYP2D6 inhibitors 3

Special Populations

Adolescents

• Assess for substance use before starting treatment 2
• Consider atomoxetine to minimize abuse potential 2
• Ensure medication coverage for symptom control while driving 2

Pregnancy

• Limited data available on use during pregnancy 2
• No increased risk for major congenital malformations identified 2
• Recent large study showed no increased risks for long-term neurodevelopmental outcomes 2

Breastfeeding

• No published studies on atomoxetine during breastfeeding 2
• Likely present in human milk due to pharmacokinetics 2
• Caution advised during breastfeeding 2

Practical Considerations

• Not a controlled substance (unlike stimulants) 5
• Negligible risk of abuse or diversion 5
• Requires fewer prescription refill restrictions than stimulants 5
• Discontinuation rates of 3.5% vs 1.4% for placebo in clinical trials 6

Common Pitfalls to Avoid

• Expecting immediate results (atomoxetine takes 6-12 weeks for full effect) 2
• Failing to monitor for suicidal ideation, especially in the first few months 2, 3
• Not considering drug interactions with CYP2D6 inhibitors 2
• Overlooking the need for dose adjustment in poor CYP2D6 metabolizers 2
• Inadequate monitoring of cardiovascular parameters 3

By understanding these prescribing guidelines for atomoxetine, clinicians can make informed decisions about when to use this medication and how to monitor patients effectively to optimize outcomes while minimizing risks.