Switching ADHD Medications: A Structured Approach
When switching ADHD medications, adjustment and changes of the pharmacological treatment regimen are the rule and not the exception, with systematic switching protocols recommended based on the reason for the change. 1
Primary Switching Algorithm
When Methylphenidate Fails After Adequate Trial
If no desired benefit is observed after adequate treatment (dosage and duration) with methylphenidate, lisdexamfetamine should be preferred as the next option over non-stimulants. 1
- This represents switching within the stimulant class before moving to non-stimulants 1
- Approximately 50% of non-responders to methylphenidate will respond to atomoxetine therapy, and approximately 75% of responders to methylphenidate will also respond to atomoxetine 2
- In clinical practice, 41% of medication-naive adults with ADHD require switching from their initially prescribed stimulant family to the alternative one within 90 days due to poor tolerability 3
Switching Methods Between Stimulants
Stimulant medications can be effectively titrated and switched on a 3- to 7-day basis due to their immediate onset of action. 1
- Because stimulant medication effects are seen immediately, trials of different doses or different stimulants can be accomplished in a relatively short time period 1
- No cross-tapering is required when switching between stimulant families due to rapid onset and offset 1
Switching to Non-Stimulants
Methylphenidate to Atomoxetine
Atomoxetine may be initiated by a schedule of dose increases and cross-tapering with methylphenidate, with co-administration during the switching period without undue concern for adverse events. 2
- A slow titration schedule with divided doses minimizes the impact of adverse events within the first several weeks of treatment 2
- Monitoring of blood pressure and heart rate is necessary during co-administration 2
- A trial period of at least 6-8 weeks, perhaps longer, is recommended before evaluation of the overall tolerability and efficacy of atomoxetine 2
- Atomoxetine requires 6-12 weeks until full effects are observed, compared to stimulants' immediate onset 1
When to Consider Non-Stimulants First-Line
Non-stimulants should be considered as first-line options in specific clinical scenarios: 1
- Comorbid substance use disorders 1
- Disruptive behavior disorders 1
- Tic/Tourette's disorder 1
- Comorbid sleep disorder (for alpha-2 agonists) 1
- Active substance abuse disorder 4
- Severe anxiety or patient/family preference 4
Monitoring During Switches
Parameters to Track
Regular monitoring should include pulse, blood pressure, weight, height (in children), and symptom response using standardized rating scales. 1, 4
- For atomoxetine specifically, monitor for suicidality and clinical worsening 1
- For alpha-2 agonists (clonidine, guanfacine), monitor for somnolence/sedation, fatigue, and hypotension 1
- Stimulants require monitoring for decreased appetite, sleep disturbances, increased blood pressure and pulse, and headaches 1
Common Pitfalls to Avoid
Do not abandon stimulants prematurely without adequate dose optimization and formulation trials. 5
- Stimulant optimization is an effective strategy to increase response before switching 5
- Consider time-action properties of stimulants and wearing-off effects before declaring treatment failure 5
- Poor adherence, excessive focus on comorbid non-ADHD symptoms, and tolerance should be evaluated before switching 5
Do not expect immediate results when switching to non-stimulants. 1, 2
- Atomoxetine requires 6-12 weeks for full therapeutic effect 1
- Alpha-2 agonists require 2-4 weeks until effects are observed 1
- Patients and families must be educated about this delayed onset to prevent premature discontinuation 2
Special Populations
Pregnancy and Postpartum
If taking a psychostimulant during pregnancy, engage in risk-benefit discussion regarding continuing the current dose or considering intermittent use rather than switching medications. 1
- Another possibility is switching from stimulants to bupropion in the perinatal period, particularly for individuals requiring treatment for co-occurring depression 1
- However, bupropion is not as efficacious as stimulants for ADHD treatment 1
- Atomoxetine has no available safety data in the perinatal context 1