After Atomoxetine Trial Failure: Next Steps in ADHD Treatment
After atomoxetine (Strattera) trial failure in a patient with ADHD, the most appropriate next step is to initiate treatment with a stimulant medication, specifically either methylphenidate or amphetamine, as these have higher efficacy rates and are considered first-line treatments for ADHD. 1, 2
Understanding Atomoxetine Failure
Before proceeding to the next treatment option, it's important to verify that the atomoxetine trial was adequate:
- Ensure proper dosing was achieved (target dose of 1.2 mg/kg/day, maximum 1.4 mg/kg/day or 100 mg/day) 2
- Confirm adequate trial duration (6-12 weeks) as atomoxetine has a delayed onset of full therapeutic effect 1, 2
- Rule out adherence issues or drug interactions (especially with CYP2D6 inhibitors) 2
Treatment Algorithm After Atomoxetine Failure
First Option: Stimulant Medications
- Methylphenidate or amphetamine formulations should be tried next, as they have larger effect sizes compared to non-stimulants 1
- Patients with ADHD may respond to either amphetamine or methylphenidate with an overall very high response rate when both psychostimulants are tried 1
Second Option: Alternative Non-Stimulants
If stimulants are contraindicated or not preferred:
- Alpha-2 adrenergic agonists (guanfacine or clonidine) can be considered 1
- These medications have a faster onset of action (2-4 weeks) compared to atomoxetine (6-12 weeks) 1
- May be particularly helpful for patients with comorbid sleep disturbances 1
Third Option: Combination Therapy
- Consider adding guanfacine or clonidine to a stimulant medication
- Both have been approved "as adjunctive therapy to stimulant medications" in the USA 1
- This combination can increase treatment effects and/or decrease adverse effects of stimulants 1
Special Considerations
Comorbidities
- For patients with tic disorders or Tourette's syndrome: Alpha-2 agonists may be beneficial 1
- For substance use disorders: Non-stimulants remain preferred over stimulants 1
- For anxiety disorders: Consider alternative non-stimulants or careful stimulant trial 1
Monitoring During Transition
- When switching to stimulants, monitor for:
Common Pitfalls to Avoid
- Inadequate trial duration: Not waiting long enough for atomoxetine to reach full effect before declaring failure 2
- Suboptimal dosing: Failing to reach the target dose of 1.2-1.4 mg/kg/day 2
- Overlooking comorbidities: Not considering how comorbid conditions might affect treatment choice 1
- Forgetting multimodal approach: Pharmacological treatment should always be part of a comprehensive treatment plan that includes psychoeducation and psychosocial interventions 1
Remember that while atomoxetine has a modest effect size (SMD = -0.33 to -0.40) 3, stimulants generally show larger effect sizes and higher response rates. Approximately 50% of non-responders to atomoxetine will respond to stimulant therapy 4, making stimulants the logical next step in the treatment algorithm.