Generic Name

Strattera

Mechanism

Strattera (atomoxetine) is a selective norepinephrine reuptake inhibitor (NRI).
• Increases extracellular norepinephrine and dopamine in the prefrontal cortex by blocking the norepinephrine transporter (NET).
• Unlike stimulants, it does not cross‑activate the dopaminergic reward pathway, reducing abuse potential.
• The primary therapeutic effect is attenuation of attention‑deficit hyperactivity disorder (ADHD) symptoms through enhanced executive function and inhibitory control.

Pharmacokinetics

• Absorption: ~85 % oral bioavailability; peak plasma concentration (Cmax) 3–8 h post‑dose.
• Metabolism: Primary route via CYP2D6 to active metabolites; the polymorphic enzyme leads to *poor*, *intermediate*, or *normal* metabolizer phenotypes affecting clearance.
• Half‑life: 5–10 h in normal metabolizers; 2–4 h in poor metabolizers.
• Excretion: 95 % via urine (80 % renal, 15 % biliary).
• Drug interactions: Strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) heighten plasma levels; concomitant use with MAO inhibitors contraindicated.

Indications

• ADHD in children (≥6 y), adolescents (≥12 y), and adults.
• Approved as an alternative to stimulants for patients with risk factors for substance misuse or with comorbid tic disorders (benign in tic presence).

Contraindications

• Type I hypersensitivity to atomoxetine.
• Concurrent MAO‑I therapy (all types) – risk of fatal serotonin syndrome.
• Severe cardiovascular disease (e.g., uncontrolled hypertension, tachyarrhythmias).
• Glaucoma, significant hepatic impairment (Child‑Pugh B/C).
• Black‑box warning: Serious cardiovascular adverse events (myocardial infarction, sudden death) in patients with pre‑existing heart disease.

Dosing

• Initial dose: 0.45 mg/kg/day on Day 1–2 (or 20 mg twice daily).
• Week 2: increase to 0.5–0.7 mg/kg/day (maximum 40 mg/day adult).
• Adults may titrate up to 80 mg/day if clinically justified, monitoring for tolerance.
• Extended‑release (ER) formulation once daily in the morning; immediate‑release (IR) two‑treatments.
• Dietary considerations: Food does not significantly alter absorption; however, higher fat meals delay Cmax slightly.

Adverse Effects

• Common (≥10 %):
• Nausea, dry mouth, fatigue, decreased appetite, weight loss, insomnia, GI upset, abdominal pain.
• Serious (≤1 %):
• Cardiovascular (palpitations, tachycardia, hypertension, arrhythmia).
• Hepatotoxicity (elevated transaminases, jaundice).
• Neuropsychiatric (suicidal ideation, agitation, mood changes).

Monitoring

• Baseline: CBC, CMP, fasting lipids, BP, HR, weight, growth metrics (in pediatric patients).
• Follow‑up (2–4 weeks): BP, HR, weight changes; repeat CMP if liver enzymes ≠ baseline.
• Periodic: UPDRS (in dopamine‑responsive populations), screening for suicidal thoughts (especially in 10–24 y).
• Titration logs to document dose adjustments and symptom response.

Clinical Pearls

• Start low; titrate up: Rapid titration increases GI side‑effects; a 1–2 week interval between increments helps tolerance.
• CYP2D6 genotype matters: Poor metabolizers require a √2 lower dose to avoid supratherapeutic levels.
• Non‑stimulant advantage: Superior in children with tic disorders, less risk of rebound hypertension.
• Combination therapy: Augmenting atomoxetine with a stimulant may be considered when monotherapy fails, allowing lower doses of stimulant.
• Growth monitoring: In children, a 2–5 % relative weight loss is common; counsel families and consider switching to IR if appetite issues persist.
• Cardiac precautions: In patients with borderline hypertension, hold dose if BP ≥140/90 mm Hg for >48 h before reevaluation.
• Post‑marketing case reports: Rare reports of sudden death highlight need for vigilance in patients with cardiac pathology; counsel patients on warning signs.

Strattera thus offers a non‑abusable, once‑daily option for ADHD management, with a distinct pharmacologic profile and a specific safety net requiring targeted monitoring.