Introduction
Strattera (atomoxetine hydrochloride) is a selective norepinephrine reuptake inhibitor (SNRI) approved by the FDA for the treatment of attention-deficit/hyperactivity disorder (ADHD). Unlike stimulant medications commonly used for ADHD, Strattera is classified as a non-stimulant medication, making it a valuable alternative for patients who cannot tolerate or have contraindications to stimulant therapies.
Mechanism of Action
Atomoxetine works by selectively inhibiting the presynaptic norepinephrine transporter in the prefrontal cortex. This inhibition increases extracellular concentrations of norepinephrine and dopamine in specific brain regions, particularly the prefrontal cortex, but not in the nucleus accumbens. The increased availability of these neurotransmitters improves attention, reduces impulsivity, and decreases hyperactivity in patients with ADHD. Unlike stimulants, atomoxetine does not appear to have significant effects on the serotonin transporter.
Indications
- Treatment of attention-deficit/hyperactivity disorder (ADHD) in children 6 years and older, adolescents, and adults
- May be used as monotherapy or as an alternative when stimulant medications are not appropriate
Dosage and Administration
Initial Dose:- Children and adolescents ≤70 kg: 0.5 mg/kg/day, increase after minimum of 3 days to target dose of 1.2 mg/kg/day
- Children and adolescents >70 kg and adults: 40 mg/day, increase after minimum of 3 days to target dose of 80 mg/day
- Maximum recommended daily dose: 100 mg for patients >70 kg
- May be administered once daily in the morning or divided twice daily
- Hepatic impairment (Child-Pugh Class B): Reduce dose to 50% of normal
- Hepatic impairment (Child-Pugh Class C): Reduce dose to 25% of normal
- Poor CYP2D6 metabolizers: Initial dose of 0.5 mg/kg/day, maximum dose of 1.2 mg/kg/day
Pharmacokinetics
Absorption: Well absorbed orally, bioavailability 63-94%, not affected by food Distribution: Volume of distribution 0.85 L/kg, protein binding 98% (primarily albumin) Metabolism: Extensive hepatic metabolism primarily via CYP2D6 to 4-hydroxyatomoxetine (active metabolite) Elimination: Half-life 5.2 hours in extensive metabolizers, 21.6 hours in poor metabolizers. Primarily renal excretion (80%) as metabolitesContraindications
- Hypersensitivity to atomoxetine or any component of the formulation
- Use within 14 days of MAO inhibitor therapy due to risk of serotonin syndrome
- Narrow-angle glaucoma
- Severe cardiovascular disorders that might be exacerbated by increases in blood pressure or heart rate
Warnings and Precautions
Black Box Warning: Increased risk of suicidal ideation in children and adolescents Hepatotoxicity: Severe liver injury reported, monitor for jaundice, dark urine, or right upper quadrant pain Cardiovascular Effects: May increase blood pressure and heart rate, monitor regularly Psychiatric Effects: May exacerbate psychotic symptoms, manic episodes, or aggressive behavior Growth Suppression: Monitor height and weight in pediatric patients Urinary Retention: May cause difficulty initiating urination or urinary retentionDrug Interactions
Strong CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine): Increase atomoxetine concentrations 5-8 fold, reduce atomoxetine dose MAO inhibitors: Contraindicated due to risk of serotonin syndrome Pressor agents: May potentiate effects on blood pressure Albuterol: May increase cardiovascular effects CNS stimulants: Additive effects possibleAdverse Effects
Common (>10%): Decreased appetite, nausea, vomiting, fatigue, dizziness, irritability, mood swings Less common (1-10%): Insomnia, abdominal pain, constipation, dyspepsia, hot flashes, palpitations Serious (<1%): Suicidal ideation, severe liver injury, priapism, angioedema, urticaria, cardiovascular eventsMonitoring Parameters
- Height and weight in pediatric patients (every 3-6 months)
- Blood pressure and heart rate at baseline, after dose increases, and periodically during treatment
- Liver function tests if symptoms of hepatic dysfunction occur
- Mental status and mood changes, particularly during initial treatment and dose adjustments
- ADHD symptom assessment using standardized rating scales
Patient Education
- Take consistently with or without food
- Do not crush or chew capsules; swallow whole
- Report any thoughts of self-harm, unusual behavior, or mood changes immediately
- Monitor for signs of liver problems (yellowing skin/eyes, dark urine, abdominal pain)
- May cause dizziness or drowsiness; use caution when operating machinery
- Inform all healthcare providers about Strattera use before starting new medications
- Keep medication securely stored away from children
References
1. FDA Prescribing Information: Strattera (atomoxetine hydrochloride) 2. Michelson D, et al. Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry. 2002;159(11):1896-1901 3. Kratochvil CJ, et al. Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry. 2002;41(7):776-784 4. Garnock-Jones KP, Keating GM. Atomoxetine: a review of its use in attention-deficit hyperactivity disorder in children and adolescents. Paediatr Drugs. 2009;11(3):203-226 5. UpToDate: Atomoxetine drug information 6. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Atomoxetine monograph