Generic Name

Atomoxetine

Brand Names

Strattera®) is a selective norepinephrine reuptake inhibitor (NRI) approved primarily for the treatment of attention‑deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. Unlike stimulants, it does not produce euphoria or have a high abuse potential, making it a useful alternative for patients with contraindications or concerns regarding stimulant therapy.

Mechanism

• Selective inhibition of the norepinephrine transporter (NET), increasing extracellular norepinephrine and dopamine in prefrontal cortical regions.
• Minimal activity at dopamine transporter (DAT), serotonin transporter (SERT), or adrenergic receptors, accounting for its distinct side‑effect profile.
• Enhances cortical executive function and attentional control, contributing to its efficacy in ADHD symptom relief.
• The therapeutic actions are delayed relative to stimulants, often requiring a few weeks to achieve optimal benefit.

Pharmacokinetics

• Absorption: Oral bioavailability ≈ 53 %; peaked plasma concentration (Tmax) 3‑4 h after dosing.
• Distribution: Protein‑binding ~ 80 %, primarily to albumin; mean volume of distribution ~ 200 L.
• Metabolism: First‑pass hepatic oxidation via CYP2D6 → active metabolite GM‑3115; metabolic rate highly polymorphic (poor, intermediate, extensive, ultrarapid metabolizers).
• Elimination: Renal excretion of metabolites; elimination half‑life 5 h (rapid metabolizers) to 18 h (poor metabolizers) with steady‑state trough levels 6‑12 h after dosing.
• Drug interactions: Strong inhibitors (e.g., paroxetine) or inducers (e.g., carbamazepine) of CYP2D6 significantly alter plasma exposure; avoid concomitant use of monoamine oxidase inhibitors (MAOIs) within 14 days.

Indications

• ADHD in pediatric (≥6 y), adolescent, and adult populations.
• Off‑label use: stimulant‑resistant ADHD, certain mood‑stabilizing adjunct in bipolar disorder (limited evidence).

Contraindications

• Contraindications: Severe hypertension, cardiovascular disease (e.g., cardiomyopathy, valvular heart disease), uncontrolled tachyarrhythmias, or a history of pheochromocytoma.
• Warnings:
• Hypertension – must monitor blood pressure (BP) and heart rate (HR) regularly.
• Supine Hypertension – avoid upright posture after dosing; consider split dosing.
• Suicidal Ideation – patients (especially <25 y) may develop depressive or suicidal thoughts; monitor with C-SSRS or equivalent scales.
• CYP2D6 Polymorphisms – poor metabolizers may experience increased risk of tachycardia, insomnia, and GI upset; consider dose adjustment.

Dosing

• Children (6–11 y): Start 0.5 mg/kg/day (max = 1 mg/kg/day), divided qHS.
• Adolescents and Adults:
• Start 18 mg/day; increase by 18 mg increments every 3–7 days as needed, up to a typical maximum of 90–100 mg/day (unchanged or divided into two daily doses).
• Alternate-day dosing is acceptable for titration or maintenance if side‑effects emerge.
• Take with or without food; prolong half‑life when taken on an empty stomach.
• Switching: Gradual tapering to avoid rebound hypertension or insomnia when discontinuing.

Adverse Effects

• Common:
• ↑↑Cough, dizziness, insomnia, anorexia, abdominal pain, nausea, rhinorrhea, headache, dry mouth.
• Serious:
• Hypertension or tachycardia (especially in poor CYP2D6 metabolizers), cardiac arrhythmias, liver enzyme elevation, drug‑induced suicidality.
• Visual impairment (rare retinal detachment) and anxiety exacerbation.
• Cerebral ischemia events reported in case series (rare).

Monitoring

• Blood Pressure & Heart Rate: Every 1–2 weeks for the first 3 months; adjust dose or discontinue if >135/85 mmHg or HR >110 bpm.
• Weight & Growth (pediatrics): Monthly during the first 6 months of therapy.
• Liver function tests: Baseline and every 3–6 months; check for elevated ALT/AST.
• CYP2D6 genotyping: Consider if poor or ultrarapid metabolism suspected (e.g., atypical side‑effect profile).
• Suicidal ideation screening: At baseline and every clinical encounter for patients under 25 y.
• Respiratory: Watch for REM sleep‑related symptoms (REM sleep behaviour disorder) in older adults.

Clinical Pearls

• Metabolizer status matters: Poor CYP2D6 metabolizers may hit toxic plasma levels (>0.2 µg/mL) and should be started at the lowest dose with cautious titration.
• Elderly patients: Exercise greater caution; consider a lower maximum dose (≤75 mg/day) and close cardiovascular monitoring.
• Non‑stimulant alternative: Atomoxetine is ideal for patients with substance use disorders or where stimulant use must be avoided; however, onset is slower (~4–6 weeks).
• Switch‑to‑stimulant: Transitioning from atomoxetine to a stimulant requires a wash‑out period (≥24 h) to avoid elevated plasma catecholamines and potential hypertensive crisis.
• Persistent hypertension: If BP remains high despite dose titration, evaluate for compliance, eating habits, sleep deprivation, or dietary salt excess; consider discontinuation.
• Sleep: Splitting the dose into AM/PM can mitigate insomnia if it occurs; caffeine intake should be minimized.

These directives provide the core pharmacological principles and practical guidelines required by a medical student or clinician to safely prescribe and manage patients on Atomoxetine.