What is the proper management and dosing of Attention Deficit Hyperactivity Disorder (ADHD) medications, including Concerta (methylphenidate) and Vyvanse (lisdexamfetamine), and when to consider alternative treatments like atomoxetine and Wellbutrin (bupropion)?

ADHD Medication Management for Family Physicians

First-Line Treatment: Stimulants Are Superior

Start with either methylphenidate (Concerta) or amphetamine formulations (Vyvanse) as first-line treatment, as stimulants demonstrate superior efficacy compared to non-stimulants and over 90% of patients respond to at least one stimulant class when both are tried at optimal doses. 1, 2, 3

Concerta (Methylphenidate ER) Initiation Protocol

• Start with 18 mg once daily in the morning (or 5-10 mg for immediate-release formulations if using those) 1, 4
• Titrate by 18 mg increments weekly based on response and tolerability 1, 4
• Maximum dose is 72 mg/day for extended-release formulations 1, 4
• Do NOT calculate dose by mg/kg - dose variations are not correlated to weight or height 2
• Duration of action: approximately 12 hours 3

Vyvanse (Lisdexamfetamine) Initiation Protocol

• Start with 30 mg once daily in the morning with or without food 5
• Titrate in 10-20 mg increments at weekly intervals 5
• Maximum dose is 70 mg/day 5
• Avoid afternoon doses due to insomnia risk 5
• Vyvanse is a prodrug converted to dextroamphetamine, providing approximately 12 hours of coverage with minimal abuse potential compared to immediate-release amphetamines 1, 5, 3

Critical Pre-Treatment Assessment

Before initiating any stimulant:

• Screen for cardiovascular disease - obtain baseline blood pressure, pulse, and assess for symptomatic heart disease through careful history, family history of sudden death or ventricular arrhythmia, and physical exam 1, 4, 5
• Screen for current or past substance abuse - this represents a relative contraindication requiring close supervision 1, 4
• Assess for tics or Tourette's syndrome - evaluate family history and clinically assess patients before initiating 1, 5
• Contraindications include: known hypersensitivity, current MAOI use or within 14 days of stopping MAOIs, symptomatic cardiovascular disease 5

Titration Strategy: The Key to Success

The single most important principle is systematic titration to maximum tolerable dose, not stopping at "standard" doses. 2

• Test 4 different dose levels during initial methylphenidate titration - this systematic approach identifies over 70% of responders 2
• Titration can be completed over 7 days, or even 3 days in urgent situations, as stimulant effects are immediate 2
• The goal is the maximum dose that controls symptoms without intolerable side effects, not a predetermined "target dose" 2
• Schedule monthly visits minimum until symptoms stabilize 2, 4
• Assess both efficacy AND side effects at each dose adjustment using standardized rating scales 2, 4

When to Switch Stimulant Classes

If the first stimulant fails, switch to the alternative stimulant class (methylphenidate to amphetamine or vice versa) before considering non-stimulants. 2, 4, 6

• More than 90% of patients respond to at least one stimulant when both methylphenidate AND amphetamines are tried at optimal doses 2
• Patients receiving usual community care get worse outcomes than those with optimal medication management, primarily due to insufficient doses and inadequate monitoring 2

Second-Line: Atomoxetine (Non-Stimulant)

Consider atomoxetine when:

• Stimulants are contraindicated, not tolerated, or ineffective after trying both classes 4, 3, 7
• Active substance use disorder is present - atomoxetine has no abuse potential 1, 7
• Diversion risk is high (adolescents, college students) 1
• Comorbid anxiety is prominent 1

Atomoxetine Dosing

• Start with 40 mg/day 4
• Titrate to maximum of 100-120 mg/day (or 1.4-1.8 mg/kg) 1, 4
• Slower onset of action compared to stimulants - allow 4-6 weeks for full effect 7
• Monitor for suicidal ideation, particularly in first months of treatment or after dose changes 8

Third-Line: Bupropion (Wellbutrin)

Bupropion is a second-line, non-stimulant alternative when stimulants and atomoxetine have failed or are contraindicated. 4, 6, 8

Bupropion XL Dosing

• Start with 150 mg once daily in the morning 4
• Titrate to maintenance dose of 150-300 mg daily 4
• Maximum dose is 450 mg/day 4

Critical Bupropion Safety Considerations

• Screen for seizure risk factors - bupropion lowers seizure threshold 4
• Contraindicated in: eating disorders, seizure history, abrupt alcohol/benzodiazepine withdrawal 4
• Do NOT combine bupropion with stimulants until further safety data are available 4

Essential Side Effect Monitoring

Monitor at every visit during titration and regularly during maintenance:

• Cardiovascular: blood pressure and heart rate elevation 2, 4, 8
• Appetite suppression and weight loss - particularly concerning in preschool-aged children 2, 5
• Sleep disturbances - insomnia is common 2, 5
• Gastrointestinal symptoms - nausea, abdominal pain 2, 5
• Psychiatric symptoms: irritability, mood changes, anxiety 5
• With atomoxetine specifically: suicidal ideation, agitation, unusual behavior 8

Special Populations: Adolescents and Diversion Risk

For adolescents (ages 12-18):

• Screen for substance abuse before initiating treatment 1
• Monitor for signs of medication diversion - misuse by patient, parents, or peers 1
• Consider formulations with lower abuse potential: Vyvanse (prodrug requiring metabolism), Concerta (OROS delivery system), or non-stimulants like atomoxetine 1
• Ensure medication coverage while driving - use longer-acting formulations or late-afternoon short-acting doses 1

Critical Pitfalls to Avoid

• Do NOT start at excessively high doses - this increases side effects and reduces adherence 2, 4
• Do NOT underdose - most treatment failures in community practice result from insufficient doses 2
• Do NOT skip the alternative stimulant class before moving to non-stimulants 2, 4
• Do NOT allow less than one week between dose adjustments to properly evaluate response 2, 4
• Do NOT abruptly discontinue stimulants for "drug holidays" during important events - symptoms return rapidly 4
• Do NOT calculate methylphenidate doses by weight - this is not evidence-based 2

Maintenance Considerations

• Long-acting formulations (Concerta, Vyvanse) are superior for adherence compared to immediate-release formulations 4, 3
• Afternoon doses of methylphenidate may need to be higher than morning doses to prevent symptom attenuation later in the day 4
• Continue monthly monitoring until stable, then can extend to every 3 months 2, 4
• Reassess cardiovascular parameters regularly during maintenance treatment 8