Strattera
Why Single Out Strattera?
Strattera® (generic name atomoxetine) was the first non-stimulant granted FDA approval for attention-deficit/hyperactivity disorder (ADHD) in both children and adults (2002). Its unique status matters for three common clinical scenarios:
- Comorbid tics – atomoxetine does not aggravate motor or vocal tics, whereas stimulants occasionally can.
- Prominent anxiety – it raises norepinephrine and dopamine mainly in the prefrontal cortex, avoiding the rapid “buzz” in the striatum that fuels jitteriness in anxious patients.
- Misuse potential – Strattera is not a controlled substance, so diversion and abuse monitoring are simplified for families, schools and prescribers.
In the pages that follow you will learn how atomoxetine works, how quickly to expect results, optimal dosing strategies, and a psychiatrist-style checklist for side-effect management – all in plain English.
Strattera at a Glance
| Feature | Strattera (atomoxetine) | Methylphenidate / Amphetamine stimulants |
|---|---|---|
| FDA approval | 2002; first generics 2017 | 1955–2000 (multiple) |
| Schedule / abuse | Not scheduled | Schedule II (US) |
| Median onset of benefit | 3–6 weeks | 20–60 minutes |
| “Much improved” on ADHD-RS | ~50% at 6 weeks | 60–80% |
| Labelled age range | ≥ 6 years | ≥ 6 years (IR); ≥ 3 years (some ER) |
Guideline Position
- American Academy of Pediatrics (AAP 2019): first-line along with stimulants for children 6–12; second-line for adolescents if stimulants fail or are contraindicated.
- NICE (UK) 2024 review: second-line in children, but may be first-line when tics, anxiety or substance-misuse risk dominate.
- CADDRA (Canada) 2021: second-line, yet emphasises 24-hour coverage and low diversion risk.
How Atomoxetine Works
Primary Mechanism
Atomoxetine is a selective norepinephrine re-uptake inhibitor (NRI). By blocking the presynaptic norepinephrine transporter (NET) it raises norepinephrine levels – and, indirectly, dopamine – in the prefrontal cortex, the brain region governing attention, working memory and emotional impulse control.
Pharmacokinetics
- Absorption: oral bioavailability ≈ 63%; peak plasma at 1–2 h with food.
- Half-life:
- Extensive CYP 2D6 metabolizers: ~5 h
- Poor CYP 2D6 metabolizers: ~24 h – explaining why some patients tolerate once-daily dosing easily while others fade by late afternoon.
- Protein binding: 98% (albumin), negligible displacement interactions.
Metabolism & Genetics
Atomoxetine is oxidised almost exclusively by CYP 2D6. Gene variants fall into four phenotypes:
| Phenotype | Prevalence | Exposure (AUC) vs normal | Clinical note |
|---|---|---|---|
| Poor metabolizer (PM) | 5–10% Caucasian | ↑ ~450% | Start half-dose; slower titration |
| Intermediate (IM) | 10–15% | ↑ ~200% | Consider gentler titration |
| Extensive (EM) | 65–70% | reference | “Standard” protocol |
| Ultrarapid (UM) | 2–5% | ↓ >50% | May need split dosing or max weight-based dose |
When to order pharmacogenomics?
History of extreme sensitivity or, conversely, non-response at full weight-based doses; concurrent use of b 2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine).
How Fast Does Strattera Work?
| Timeline | Typical Clinical Milestone |
|---|---|
| Days 1–3 | Minimal observable change – set expectations: patience is required. |
| Week 2 | Early improvements in task initiation and morning routine, mainly in ultrarapid metabolizers or those on higher mg/kg doses. |
| Weeks 4–6 | 40–60% of patients score “much improved” on clinician-rated ADHD-RS. |
| Week 8 | Plateau for most responders; lack of benefit by 8 weeks at max weight-based dose = declare non-response and consider switch. |
Factors Influencing Onset
- Under-dosing (mg/kg below guideline) – most common reason for “it doesn’t work.”
- CYP 2D6 phenotype – PMs actually reach higher levels sooner but may experience somnolence before benefit.
- Concomitant stimulants – sometimes used briefly to “bridge” early weeks in severe cases.
Strattera Dosage & Titration
Weight-Based Targets
- Children & adolescents (≤70 kg):
- Start 0.5 mg/kg/day → increase every 3–7 days to 1.2 mg/kg/day (max 1.4 mg/kg or 100 mg, whichever lower).
- Adults (>70 kg):
- Start 40 mg/day → 80 mg after ≥3 days → 100 mg if partial.
Once-daily vs split dosing
- AM only: simpler, fewer missed doses, slight appetite suppression.
- AM + late-afternoon: useful when morning wear-off or PM hyperactivity persists.
Missed-Dose Logic
- < 6 h late: take immediately.
- > 6 h late: skip; never “double-up.”
- Interruptions ≥1 week: restart at half previous dose to minimize GI upset.
Special Scenarios
- Hepatic impairment: reduce dose by 50% (moderate) or 75% (severe).
- b CYP 2D6 inhibitor co-administration: do not exceed 80 mg/day.
Managing Side-Effects – Psychiatrist’s Checklist
| System | Common Effects | Mitigations |
|---|---|---|
| Gastro-intestinal | Nausea, abdominal pain | Dose with a protein-rich breakfast; divide dose; ginger chews. |
| Sleep / Fatigue | Early somnolence (esp. PMs) or insomnia | Switch to bedtime dosing or split; add AM light therapy; screen for underlying depression. |
| Mood / Irritability | Agitation, tearfulness | Track GAD-7 / PHQ-9; small dose reduction or cautious SSRI augmentation. |
| Cardiovascular | ↑ BP 2–4 mm Hg; ↑ pulse 5–10 bpm | Baseline vitals, repeat at 4 weeks then every 6 months. |
Rare but Serious
- Hepatotoxicity – itching, dark urine, RUQ pain. Action: stop drug, order LFTs. Incidence ≈ 1 per 100,000 patient-years.
- Suicidal ideation – FDA black-box for children & young adults; monitor with Columbia-SAS.
Monitoring Table
| Visit | Who checks | What |
|---|---|---|
| Baseline | Clinician | BP, pulse, weight, PHQ-9, LFTs (if liver history) |
| 4 weeks | Clinician / nurse | BP, pulse, weight; side-effect review |
| 6–8 weeks | Clinician | ADHD-RS, CGI-I, labs if symptomatic |
| Q 6 months | PCP | BP/pulse, weight, growth chart, mental-health screen |
Weight Changes on Strattera — Evidence Review
- Pediatric RCTs: mean −0.3 kg vs placebo at 12 weeks – statistically small, but growth velocity unaffected long-term.
- Adult trials: weight-neutral overall; ~5% report mild loss (>2 kg).
- Mechanisms: modest appetite suppression, fewer impulsive snack choices after executive control improves.
Practical tips:
- Plot height/weight every 6 months.
- Encourage front-loading calories (breakfast & lunch) before PM appetite dips.
- Dietitian referral for >10% weight change or faltering growth percentile.
Strattera and Alcohol
Atomoxetine does not share hepatic metabolic pathways with alcohol, but orthostatic hypotension and sedation are additive.
- Driving simulation data show slowed reaction times when moderate alcohol (0.05% BAC) is combined with atomoxetine vs alcohol alone.
Harm-reduction advice:
- Wait ≥4 h after an evening dose before the first drink.
- Keep intake ≤1 standard drink (F) / ≤2 (M).
- Avoid binge patterns and never mix with power-tool or machinery use.
Proper Disposal of Unused Atomoxetine
Why bother? Unsecured capsules tempt curious children, and flushing active pharmaceutical ingredients pollutes water systems.
- Preferred: take-back kiosks at retail pharmacies or DEA Drug Take-Back Day events (April & October).
- If no kiosk: mix opened capsules with coffee grounds or cat litter, seal in a bag, then household trash – the drug is not on the FDA flush list.
- Update your medication list and inform your prescriber to prevent early-refill safety checks.
Special Populations & Clinical Pearls
| Scenario | Practical Pearl |
|---|---|
| ADHD + Generalised Anxiety | Atomoxetine often less activating than stimulants; transient jitter may require slower titration. |
| Autism Spectrum (ASD) | Lower irritability rates; start at 0.3 mg/kg to gauge sensory tolerability. |
| Diversion concern (teens, incarcerated) | Non-scheduled status eases school storage and prescription refills. |
| Known structural heart disease | Atomoxetine is QT-neutral, but mild BP rise warrants cardiology consult pre-start. |
| Peri-operative period | Continue to avoid rebound hyperactivity unless hypotension anticipated; discuss with anaesthesiologist. |
Frequently Asked Questions
Yes. Caffeine and atomoxetine do not share metabolic pathways. Be mindful of combined pulse and anxiety effects; cap coffee at usual personal tolerance.
Skip until next scheduled time. Do not double. Missing 1–2 days rarely causes withdrawal but you may notice faded focus by Monday morning.
Yes for active ingredient and FDA bioequivalence standards (80–125% AUC). Inert fillers differ; a minority notice GI feel changes.
Early norepinephrine rise can create fatigue or mood lability before frontal-cortex dopamine benefit emerges. Usually settles by week 3; communicate with your prescriber if troublesome.
Resources & References
Guidelines
- AAP Clinical Practice Guideline (2019)
- NICE ADHD Guideline NG87 (reviewed 2025)
- CADDRA Canadian ADHD Practice Guideline 4.1 (2021)
Patient handouts
- CHADD Atomoxetine Fact Sheet
- CDC ADHD Treatment Recommendations
Key trials & reviews
- Michelson D et al., Pediatrics 2002 – pivotal RCT
- Bangs ME et al., CNS Drugs 2014 – meta-analysis of 29 trials
- Childress A C et al., 2023 real-world registry (U.S. claims)
Regulatory documents
- FDA Full Prescribing Information (2022 revision)
Key Takeaways
Strattera carves a valuable niche in ADHD care: steady, 24-hour symptom control with low abuse potential and anxiety-friendly pharmacology. Success hinges on realistic timelines (think weeks, not hours), weight-based dosing, and vigilant monitoring of side-effects and cardiovascular parameters.
For many families and adult patients, atomoxetine is the linchpin of a partnership-based treatment plan that may also include behaviour therapy, lifestyle tweaks and – when needed – stimulant or SSRI add-ons.
Looking for more? See our companion hubs on ADHD Stimulants and Behaviour-First Strategies for next-level optimisation.