atomoxetine

General Information

Atomoxetine is a non-stimulant medication for ADHD and functions as a selective norepinephrine reuptake inhibitor. It is not a controlled substance and is often considered when stimulant misuse/diversion risk, tics, or insomnia concerns limit stimulants.

Onset is slower than stimulants (often several weeks). Benefit depends on consistent daily dosing, and early follow-up is commonly used to support adherence and manage tolerability (GI upset, fatigue, insomnia).

Atomoxetine has a boxed warning for increased risk of suicidal ideation in children and adolescents; mood/suicide screening is typically included in pediatric use, and families should be informed about warning signs.

In serious mental illness, atomoxetine may be preferred over stimulants when activation risk is high, but it can still worsen anxiety and (rarely) trigger mania; close monitoring is typical if bipolar spectrum illness is present.

The atomoxetine compare view, the evidence feed, and the print page can support counseling and monitoring conversations.

Atomoxetine is a strong option when stimulant diversion risk is high or when a patient prefers a non-controlled medication. The key failure mode is stopping too early: onset is delayed, so expectation-setting, thoughtful titration, and reassessment after an adequate trial are important.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Selective norepinephrine reuptake inhibition increases noradrenergic signaling in cortical circuits relevant to attention and impulse control.

Benefits develop over weeks rather than hours; scheduled follow-up and objective measures (school/work performance, fewer errors, less impulsivity) are useful to evaluate response.

Compared with stimulants, atomoxetine has lower misuse risk but may be limited by nausea, fatigue, insomnia, and sexual side effects.

• Norepinephrine transporter inhibition (primary).
• No direct stimulant release mechanism; not a controlled substance.

Metabolism and Pharmacokinetics

• Metabolized primarily by CYP2D6; poor metabolizers and CYP2D6 inhibitors can substantially increase exposure and prolong half-life.
• CYP2C19 contributes in some patients; variability is clinically relevant when response or side effects change after medication additions.
• Primarily excreted in urine as metabolites; routine lab monitoring is not required, but rare hepatic injury symptoms should prompt evaluation.

Dosing and Administration

• Adults often start at 40 mg/day, then increase to a target of 80 mg/day after several days to weeks; maximum recommended dose is 100 mg/day (label).
• Pediatric dosing is weight-based; titration is gradual, with appetite, sleep, and mood monitoring during dose changes.
• Once daily dosing is common; splitting the dose (BID) can reduce nausea or fatigue in some patients.
• If there is no meaningful improvement after an adequate trial at a therapeutic dose (often 6–8 weeks), reassess diagnosis and comorbidities rather than escalating indefinitely.

Monitoring & Labs

• Mood and suicidality monitoring in children/adolescents (boxed warning), especially early in treatment.
• Baseline and periodic blood pressure and heart rate (more often during titration).
• Appetite and weight tracking in children; consider growth monitoring when long-term.
• Fatigue/insomnia monitoring; dose timing or split dosing adjustments can help when limiting.
• Medication changes that affect CYP2D6 are worth reviewing when response or side effects change.

Sources: DailyMed label; guideline statements; network meta-analysis context.

Adverse Effects

Interactions

• CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) can increase exposure; lower starting doses and monitoring for side effects are common in these combinations.
• Contraindicated with MAO inhibitors; allow adequate washout.
• Additive cardiovascular effects are possible with other agents that raise heart rate or blood pressure; vitals are typically monitored during titration.

Other Useful Information

• Expectation-setting for delayed onset and follow-up within 2–4 weeks are commonly used to assess adherence, side effects, and early response.
• Objective targets (task completion, fewer errors, school reports) can help guide dose adjustments.
• When comorbid bipolar disorder is present, clinicians often stabilize mood first and monitor for activation during titration.
• Consider non-stimulant combinations thoughtfully (e.g., with alpha-2 agonists) when sleep and impulsivity remain problematic.

References

1. Strattera (atomoxetine) prescribing information — DailyMed (2026)
2. Attention deficit hyperactivity disorder (NICE guideline NG87) — NICE (2018)
3. Clinical Practice Guideline FOR THE Diagnosis, Evaluation, AND Treatment OF Attention Deficit/hyperactivity Disorder IN Children AND Adolescents — Pediatrics (2019)
4. Comparative Efficacy AND Tolerability OF Medications FOR Adhd (systematic Review AND Network Meta Analysis) — Lancet Psychiatry (2018)