Strattera Tapering Guide
atomoxetine
Boxed Warning
Increased risk of suicidal ideation in children, adolescents, and young adults with ADHD or other psychiatric disorders. Monitor closely during initial therapy and dose changes.
Overview
Atomoxetine is a selective norepinephrine reuptake inhibitor (NRI) approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. It is the first non-stimulant medication approved for ADHD.
10mg, 18mg, 25mg, 40mg, 60mg, 80mg, 100mg
Capsules: 10mg, 18mg, 25mg, 40mg, 60mg, 80mg, 100mg
Category C (risk cannot be ruled out)
Mechanism of Action
Selective inhibitor of the presynaptic norepinephrine transporter (NET), increasing synaptic norepinephrine. Minimal affinity for other neurotransmitter transporters or receptors.
Taper Notes
Short parent half-life and minimal dependence liability; classical withdrawal is uncommon, but rebound ADHD symptoms, fatigue, and dysphoria can emerge. Step down by available capsule strengths over 2–4 weeks. Slower in CYP2D6 poor metabolizers.
Maudsley Deprescribing Guidance
Atomoxetine is generally easier to discontinue than SSRIs given minimal dependence. Stepwise reductions matched to capsule strengths blunt rebound. CYP2D6 poor metabolizers (~7% of Caucasians) have 5-fold higher AUC and 10-fold longer half-life — slow the taper accordingly.
Tapering Protocol
Evidence-based phased reduction schedule. Always taper under medical supervision.
| Phase | Duration | Notes |
|---|---|---|
| Initial reductions | 2-3 weeks | Step down using available capsule strengths (e.g., 80 → 60 → 40 mg). Extensive CYP2D6 metabolizers typically tolerate larger early steps. |
| Middle reductions | 2-3 weeks | Continue stepwise reductions. Monitor for rebound ADHD symptoms and dysphoria — these can mimic untreated ADHD but typically resolve within 2 weeks. |
| Final reductions | 2-4 weeks | Step from 10 mg to off. CYP2D6 poor metabolizers warrant extended holds (3–4 weeks) at this stage given prolonged effective half-life. |
Withdrawal Timeline
1-3 days after dose reduction
3-7 days
Most rebound symptoms resolve within 1-2 weeks
Rebound ADHD symptoms and low mood may persist 2-4 weeks; uncommon beyond that
Clinical Pearls
Practical considerations for clinicians supervising Strattera tapers.
- 1Atomoxetine discontinuation is typically simpler than SSRI tapers — a 2–4 week stepdown by capsule strength is adequate for most patients.
- 2In CYP2D6 poor metabolizers or patients on strong CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion), expect slower clearance and plan a longer taper with extended hold periods.
- 3Counsel the patient that rebound focus difficulties and dysphoria mimic untreated ADHD but typically resolve within 1–2 weeks; this is not failure of the taper.
- 4Splitting the daily dose to BID for 1–2 weeks before stepping down can smooth the transition by reducing peak-trough fluctuations.
Common Withdrawal Symptoms
Interactions & Safety
Drug Interactions
- MAOIs — contraindicated within 14 days (hypertensive crisis risk)
- Strong CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) markedly increase exposure
- Albuterol and other beta-agonists may potentiate cardiovascular effects
Food Interactions
- No clinically significant food effect on AUC
- Food may reduce nausea associated with the morning dose
Contraindications
- Concurrent or recent (within 14 days) MAOI use
- Narrow-angle glaucoma
- Pheochromocytoma
Toxicity
Suicidal ideation in pediatric patients, severe hepatic injury (rare), and increased blood pressure/heart rate. Risk of QT prolongation in poor metabolizers or with CYP2D6 inhibitors.
External References
Pharmacokinetics
ADME Profile
Rapidly absorbed after oral administration, Tmax 1–2 hours. Bioavailability 63% in extensive metabolizers, 94% in poor metabolizers. Food may delay Tmax but does not affect overall exposure.
~0.85 L/kg
Extensive hepatic metabolism, primarily via CYP2D6 to 4-hydroxyatomoxetine (active, but rapidly glucuronidated). Minor contributions from CYP2C19.
Renal (>80% as conjugated 4-hydroxyatomoxetine), <3% unchanged.
~98% (primarily albumin)
~0.35 L/h/kg (extensive metabolizers); ~0.03 L/h/kg (poor metabolizers)
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