Atomoxetine Titration Schedule
For children and adolescents up to 70 kg, start atomoxetine at 0.5 mg/kg/day and increase after a minimum of 3 days to a target dose of 1.2 mg/kg/day, administered either once daily in the morning or as divided doses morning and late afternoon/early evening. 1
Initial Dosing by Weight
Children and Adolescents ≤70 kg:
- Starting dose: 0.5 mg/kg/day 1
- Minimum duration before increase: 3 days 1
- Target dose: 1.2 mg/kg/day 1
- Maximum dose: 1.4 mg/kg/day or 100 mg total daily dose, whichever is less 1
Children and Adolescents >70 kg and Adults:
- Starting dose: 40 mg/day 1
- Minimum duration before increase: 3 days 1
- Target dose: 80 mg/day 1
- After 2-4 additional weeks: May increase to maximum of 100 mg/day if optimal response not achieved 1
Titration Principles
The key principle is slow, gradual titration to minimize adverse effects and avoid overshooting the optimal dose. 2 Dosage should be increased in the smallest available increments at approximately 1-2 week intervals for medications with shorter half-lives like atomoxetine 2. The American Academy of Child and Adolescent Psychiatry recommends maintaining the initial dose for at least 1-2 weeks to assess tolerability before increasing 2, and increasing by small increments (typically 10-25 mg) no more frequently than every 1-2 weeks 2.
Important caveat: While the FDA label states a minimum of 3 days before dose increase 1, clinical practice guidelines suggest waiting 1-2 weeks between increases to better assess tolerability and avoid behavioral activation 2. This more conservative approach is particularly important in younger patients who may be more susceptible to agitation with rapid dose escalation 2.
Dosing Schedule Options
Atomoxetine can be administered as:
- Once daily in the morning (preferred for simplicity) 1
- Divided doses: Morning and late afternoon/early evening 1
Once-daily morning dosing provides continuous symptom relief lasting into evening and morning hours 3, with efficacy demonstrated throughout the day including evening and early morning behaviors 3.
Timeline for Response
Set appropriate expectations: atomoxetine requires 6-12 weeks to achieve full therapeutic effect, unlike stimulants which work within hours. 2 However, some symptom improvement may be evident as early as the first week of treatment 3. Core ADHD symptoms continue to decrease throughout the initial 8-week period with continued treatment and dose titrations 3.
A trial period of at least 6-8 weeks, perhaps longer, is recommended before evaluating overall tolerability and efficacy 4.
Special Population Adjustments
Hepatic Impairment:
- Moderate hepatic impairment (Child-Pugh Class B): Reduce initial and target doses to 50% of normal 1
- Severe hepatic impairment (Child-Pugh Class C): Reduce initial and target doses to 25% of normal 1
CYP2D6 Poor Metabolizers or Strong CYP2D6 Inhibitor Use:
- Children/adolescents ≤70 kg: Start at 0.5 mg/kg/day, increase to usual target of 1.2 mg/kg/day only if symptoms fail to improve after 4 weeks and initial dose is well tolerated 1
- Children/adolescents >70 kg and adults: Start at 40 mg/day, increase to usual target of 80 mg/day only if symptoms fail to improve after 4 weeks and initial dose is well tolerated 1
Strong CYP2D6 inhibitors include paroxetine, fluoxetine, and quinidine 1.
Monitoring During Titration
Close monitoring is essential during the first few months of treatment or at times of dose changes due to potential risks including suicidality, clinical worsening, and unusual behavioral changes 2.
Behavioral activation/agitation (including motor or mental restlessness, insomnia, impulsiveness, talkativeness, disinhibited behavior, aggression) can occur early in treatment or with dose increases 2. If side effects occur, consider returning to the previous well-tolerated dose 2.
Maintenance Dosing
For patients who achieve robust response, lower maintenance doses may be effective. Research demonstrates that patients responding to 1.2-1.8 mg/kg/day can maintain response with reduced doses of 0.5 mg/kg/day during long-term treatment 5, though this should be individualized based on symptom control.
The physician should periodically reevaluate long-term usefulness for the individual patient 1.
Discontinuation
Atomoxetine can be discontinued without tapering 1, and patients may miss occasional doses without rebound effects or discontinuation syndrome 4. However, symptoms typically return upon discontinuation 2.