How do you decide between methylphenidate and amphetamine for a patient with ADHD?

How to Decide Between Methylphenidate and Amphetamine for ADHD

Start with methylphenidate as first-line therapy, and if there is inadequate response after adequate dosing and duration, switch to an amphetamine preparation (lisdexamfetamine or mixed amphetamine salts) as the next option, as approximately 70% respond to either stimulant alone but nearly 90% respond when both classes are tried sequentially. 1, 2

Initial Stimulant Selection Algorithm

Start with Methylphenidate in Most Cases

• Both methylphenidate and amphetamines are equally effective first-line stimulants with large effect sizes for ADHD symptom reduction, but methylphenidate should be initiated first in most patients. 1, 2
• For preschool-aged children (4-5 years), methylphenidate is specifically recommended as first-line despite amphetamine having FDA approval under age 6, due to stronger evidence in this age group. 2
• Extended-release formulations should be strongly preferred over immediate-release for both medication classes due to better adherence, lower rebound effects, more consistent symptom control, and reduced diversion potential. 1, 3, 2

Consider Amphetamines as Initial Choice in Specific Populations

• For adults with ADHD, amphetamine-based stimulants are preferred over methylphenidate based on comparative efficacy studies. 3, 2
• For narcolepsy with cataplexy, amphetamine (dextroamphetamine) demonstrates superior efficacy for both excessive daytime sleepiness AND cataplexy control compared to methylphenidate, which primarily improves disease severity. 4

Titration Strategy and Dose Optimization

Methylphenidate Titration

• Start with 5 mg twice daily (after breakfast and lunch) for children, or 5 mg once daily for adults. 1
• Increase weekly by 5-10 mg increments based on symptom control and tolerability, using rating scales from teachers and parents for children, or from patient and significant others for adults. 1
• Maximum daily doses: 60 mg for adults, with some patients requiring up to 1.0 mg/kg or 65 mg total daily dose when higher doses are clearly documented as necessary without side effects. 1, 3
• The incremental benefits of methylphenidate remain constant across the FDA-licensed dose range when using flexible titration based on symptoms and tolerability, supporting titration to higher doses as needed. 5

Amphetamine/Dextroamphetamine Titration

• Start with 2.5 mg once or twice daily for children, or 2.5-5 mg for adults. 1
• Increase weekly by 2.5-5 mg increments based on response. 1
• Maximum daily doses: 40 mg for dextroamphetamine/mixed amphetamine salts, with some adults requiring up to 0.9 mg/kg. 1
• Amphetamines may require only once-daily dosing initially, with noon dose added if duration is insufficient. 1

When to Switch Between Stimulant Classes

Indications for Switching from Methylphenidate to Amphetamine

• If no desired benefit is observed after adequate treatment (appropriate dosage and duration) with methylphenidate, lisdexamfetamine should be preferred as the next option over non-stimulants. 1
• Approximately 70% of patients respond to either methylphenidate or amphetamine alone, but nearly 90% respond when both stimulant classes are tried sequentially. 1, 2
• Individual patients may respond preferentially to one stimulant class over the other due to unpredictable individual variation in response. 2

Indications for Switching from Amphetamine to Methylphenidate

• If cardiovascular adverse effects develop (tachycardia, elevated blood pressure) on amphetamines, consider switching to methylphenidate or non-stimulant alternatives. 4
• If patient has history of drug dependence or alcoholism, methylphenidate may be preferred as it has pharmacokinetic properties that reduce abuse potential compared to amphetamines. 1, 4, 6

Special Considerations Influencing Choice

Comorbid Conditions

• Anxiety is NOT a contraindication to stimulant use for either medication class, though careful monitoring is required. 3, 2
• For comorbid sleep disturbances, consider timing of doses and potentially alpha-2 agonists (guanfacine, clonidine) as adjunctive or alternative therapy. 1, 3
• For comorbid substance use disorder, screen thoroughly before prescribing any stimulant, and consider formulations with lower abuse potential or non-stimulant alternatives. 3, 2, 6, 7

Cardiovascular Monitoring Requirements

• Both stimulants require regular blood pressure and pulse monitoring, as they cause statistically significant but usually small increases (1-4 mmHg blood pressure, 1-2 bpm heart rate). 4, 2
• Screen for personal or family history of serious heart disease, heart defects, or sudden cardiac death before initiating either stimulant. 6
• If tachycardia or elevated blood pressure develops, discontinue or decrease dose, or switch to non-stimulant alternatives (atomoxetine, guanfacine, clonidine). 4

Duration of Coverage Needed

• Consider extended-release formulations that provide 8-12 hours of coverage for school/work day needs. 1
• For adolescents requiring coverage for homework, driving, and evening activities, immediate-release methylphenidate can be added in late afternoon at 30-50% of the total daily extended-release dose. 2
• Avoid dosing immediate-release stimulants after 5-6 PM to prevent sleep interference. 2

Critical Pitfalls to Avoid

• Do NOT assume lack of response to one stimulant class means failure of all stimulants; always trial the alternative class before moving to non-stimulants. 1, 2
• Do NOT underdose stimulants in clinical practice; flexible titration to higher doses as tolerated is associated with improved efficacy and acceptability. 5
• Do NOT prescribe stimulants to patients with uncontrolled hypertension, underlying coronary artery disease, or tachyarrhythmias without cardiology consultation. 1
• Do NOT abruptly discontinue if switching to alpha-2 agonists (guanfacine, clonidine), as this can cause rebound hypertension; these must be tapered. 4, 2
• Do NOT expect immediate effects from non-stimulant alternatives if switching; they require 2-12 weeks for therapeutic effect. 3, 4

Monitoring Parameters for Both Stimulant Classes

• Blood pressure and pulse at baseline and regularly during treatment (every visit during titration, then every 3 months). 4, 2, 6
• Height and weight monitoring, as both stimulants cause dose-related reductions in growth velocity. 4, 2
• Assessment for common adverse effects: decreased appetite, sleep disturbances, headaches, irritability, stomach pain. 2
• Screen for signs of misuse, diversion, or tolerance, particularly in adolescents and adults. 2, 6, 7
• Monitor for psychiatric symptoms including new or worsening anxiety, depression, psychosis, or manic symptoms. 6, 7