Atomoxetine (Strattera)

Mechanism of ActionAtomoxetine is a selective norepinephrine reuptake inhibitor (NRI). Its primary mechanism of action involves:
  1. Inhibition of Norepinephrine Transporter (NET):
    • Increases the levels of norepinephrine in the prefrontal cortex by blocking its reuptake into presynaptic neurons.
    • This enhances attention, focus, and impulse control, which are often impaired in individuals with ADHD.
  2. Non-Stimulant Properties:
    • Unlike stimulant medications, atomoxetine does not directly increase dopamine activity in the striatum, reducing the risk of misuse or dependency.
Sources:
  • UpToDate: Atomoxetine Overview
  • Swanson et al., "Pharmacokinetics and Mechanism of Action of Atomoxetine"
Clinical BenefitsAtomoxetine is primarily used for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) and has several advantages:
  1. Efficacy in ADHD:
    • Reduces symptoms of inattention, hyperactivity, and impulsivity.
    • Particularly effective in individuals who do not tolerate or respond well to stimulant medications.
  2. No Abuse Potential:
    • As a non-stimulant, it carries no significant risk of misuse or dependence.
  3. Effectiveness in Comorbid Conditions:
    • May be beneficial in patients with ADHD and anxiety disorders due to its non-stimulant nature.
  4. Once-Daily Dosing:
    • Provides symptom relief throughout the day without requiring multiple doses.
Sources:
  • NICE Guidelines for ADHD
  • FDA Prescribing Information

Dosage
  1. Initial Dosage:
    • Start at 0.5 mg/kg/day for children and adolescents, increased to a target dose of 1.2 mg/kg/day based on response and tolerability.
    • Adults typically begin at 40 mg/day, increasing to 80 mg/day after at least 3 days.
  2. Maximum Dosage:
    • Children and Adolescents: 1.4 mg/kg/day or 100 mg/day (whichever is lower).
    • Adults: 100 mg/day.
  3. Administration:
    • Taken once daily, with or without food, though some patients may benefit from divided dosing if side effects occur.
Sources:
  • FDA Guidelines for Atomoxetine
  • Clinical Pharmacology Texts

Prevalence of Side EffectsCommon Side Effects (10–30%):
  • Gastrointestinal:
    • Nausea, vomiting, decreased appetite.
  • Neurological:
    • Fatigue, dizziness, drowsiness.
  • Psychiatric:
    • Mood swings, irritability, or anxiety.
Serious Side Effects (Rare):
  1. Suicidal Ideation:
    • Black box warning for increased risk of suicidal thoughts in children and adolescents.
    • Close monitoring is essential during treatment initiation.
  2. Hepatotoxicity:
    • Rare cases of liver injury; patients should be monitored for signs of liver dysfunction (e.g., jaundice, dark urine).
  3. Cardiovascular Effects:
    • May increase blood pressure and heart rate; contraindicated in patients with severe cardiovascular disease.
  4. Severe Allergic Reactions:
    • Rare hypersensitivity reactions, including angioedema.
Sources:
  • BMJ: Atomoxetine Safety Profile
  • FDA Black Box Warnings

SummaryAtomoxetine is a non-stimulant medication offering significant benefits in treating ADHD, especially for patients who are intolerant to or at risk for misuse of stimulant medications. Regular monitoring of psychiatric, hepatic, and cardiovascular health is recommended to manage potential side effects effectively.