What are the differences between Concerta (methylphenidate) and Vyvanse (lisdexamfetamine) in terms of efficacy and side effects?

Concerta vs Vyvanse: Key Differences in Efficacy and Side Effects

Both Concerta (methylphenidate extended-release) and Vyvanse (lisdexamfetamine) are highly effective stimulants for ADHD with approximately 70% response rates, but they differ primarily in their pharmacokinetic profiles, duration of action, and abuse potential rather than in overall efficacy or side effect profiles. 1

Mechanism and Pharmacology

Vyvanse is a prodrug that must be converted to dextroamphetamine after ingestion, while Concerta uses an osmotic-release system (OROS) to deliver methylphenidate throughout the day. 2

• Vyvanse's prodrug design makes extraction of the active stimulant component more difficult, conferring lower abuse potential—particularly important in adolescents 2
• Concerta's OROS technology produces an ascending plasma drug level pattern designed to last 12 hours, equivalent to methylphenidate given three times daily 1, 3
• The conversion process required for Vyvanse activation provides a smoother, more gradual onset compared to immediate-release formulations 2

Duration of Action and Dosing

Concerta provides 12-hour coverage with once-daily morning dosing, while Vyvanse typically provides 10-13 hours of symptom control. 1, 3

• Concerta begins working within 90 minutes, with peak behavioral effects at 3 hours 1
• Vyvanse usual starting dose is 20-30 mg once daily in the morning, titrated by 10 mg weekly to maximum 70 mg daily 2
• Concerta dosing: 18 mg (equivalent to 5 mg methylphenidate three times daily), 36 mg (equivalent to 10 mg three times daily), or 54 mg (equivalent to 15 mg three times daily) 1, 3

Efficacy Profile

Both medications demonstrate robust efficacy across multiple domains of ADHD symptoms with no clinically meaningful differences in overall effectiveness. 1

• Short-term trials (typically 3 months or less) show approximately 70% response rates for stimulants as a class 1
• Both improve attention, deportment, classroom behavior, academic productivity/accuracy, and social functioning 3
• Effects persist throughout the school day and into early evening hours 3
• Both prevent the typical deterioration in behavior that occurs as the day progresses in untreated ADHD 3

Side Effect Profiles

The side effect profiles are essentially identical between the two medications, as both are CNS stimulants affecting similar neurotransmitter systems. 1

Common Side Effects (Both Medications):

• Appetite suppression: Manage by giving medication with meals and offering high-calorie snacks in the evening when effects wear off 1
• Insomnia: Distinguish whether due to medication side effect versus oppositional behavior; lower the dose or move it earlier in the day 1
• Weight loss: Small weight decrements occur during short-term trials, but long-term follow-up shows no significant impairment of final height attained 1
• Irritability: Evaluate timing (peak effect versus rebound); reduce dose accordingly 1
• Sadness/mood changes: May require dose reduction or switch to sustained-release products 1

Serious Side Effects (Extremely Rare):

• With an estimated 3 million children taking stimulants daily in the US, serious side effects occur at rates less than 1/10,000 1
• Cardiovascular effects are possible but exceedingly rare at therapeutic doses 1

Abuse Potential

Vyvanse has demonstrably lower abuse potential compared to Concerta due to its prodrug formulation. 2

• The American Academy of Pediatrics suggests Vyvanse may be preferred in adolescents specifically due to lower abuse potential 2
• Both medications are DEX Schedule II controlled substances, but Vyvanse's pharmacokinetic properties make extraction and misuse more difficult 2
• Oral administration of therapeutic doses has limited ability to induce euphoria compared to other routes 1
• Two reports indicate ADHD adolescents treated with stimulants show lower rates of substance use disorder than untreated ADHD adolescents 1

Special Considerations

Generic Formulations:

• Critical caveat: Non-OROS generic methylphenidate ER formulations are NOT equivalent to brand-name Concerta 4, 5
• Studies demonstrate clinically and statistically significant differences, with mean T-score reductions of 23 points when switching from non-OROS generic to OROS Concerta at the same dose 4
• If prescribing Concerta, specify "brand name only" or ensure the generic uses OROS technology 4, 5

Pregnancy and Breastfeeding:

• Neither medication appears associated with major congenital malformations 2, 6
• Possible small increased risks for gastroschisis (aOR 3.0), preeclampsia (aRR 1.29), and preterm birth (aRR 1.30) apply to both amphetamines and methylphenidate 2, 6
• Both are compatible with breastfeeding with appropriate infant monitoring for irritability, insomnia, and feeding difficulties 6

Clinical Decision-Making Algorithm

Choose Vyvanse when:

• Adolescent patient with concerns about diversion or abuse risk 2
• Patient or family prefers amphetamine-based medication
• Previous inadequate response to methylphenidate formulations

Choose Concerta when:

• Patient or family prefers methylphenidate-based medication
• Previous inadequate response to amphetamine formulations
• Desire for well-established OROS delivery system with extensive research base 1, 3
• Must specify brand name or OROS generic to ensure therapeutic equivalence 4, 5

Both are equally appropriate when:

• First-line stimulant treatment is indicated
• No specific contraindications exist
• Patient has no prior stimulant exposure to guide selection