What is the difference between Vyvanse (lisdexamfetamine) and Adderall (amphetamine salts)?

Key Differences Between Vyvanse and Adderall

Vyvanse (lisdexamfetamine) is a prodrug that requires enzymatic conversion to active d-amphetamine in the blood, while Adderall (mixed amphetamine salts) contains immediate-release amphetamine that is active upon ingestion. 1

Mechanism and Pharmacology

Chemical Structure

• Vyvanse is lisdexamfetamine dimesylate—a prodrug consisting of d-amphetamine covalently bonded to the amino acid l-lysine 2, 3
• Adderall contains a mixture of amphetamine salts (dextroamphetamine and levoamphetamine) that are pharmacologically active immediately 1

Activation Process

• Vyvanse remains pharmacologically inactive until red blood cells enzymatically hydrolyze it to release d-amphetamine and l-lysine 2, 4
• Adderall requires no conversion and begins working immediately after absorption 5

Pharmacokinetic Profile

• Vyvanse has a delayed onset with a lag time approximately 0.6 hours longer and reaches peak levels about 1.1 hours later than equivalent doses of d-amphetamine 5
• Adderall (immediate-release formulations) reaches peak concentrations more rapidly 5
• Both achieve similar maximal concentrations and total drug exposure (AUC) when given in equimolar doses 5

Clinical Implications

Duration of Action

• Vyvanse provides once-daily dosing with effects lasting up to 14 hours post-dose in adults, making it suitable for managing symptoms extending late into the day 4
• Adderall XR (extended-release) also provides once-daily dosing but through different controlled-release bead technology 1

Abuse Potential

• Vyvanse has theoretically lower oral abuse potential because the prodrug design limits the rate of d-amphetamine release through enzymatic hydrolysis 1, 3
• The American Academy of Pediatrics notes that lisdexamfetamine is more difficult to extract for misuse compared to immediate-release amphetamines 1
• However, research shows that when taken orally at therapeutic doses, peak subjective effects (drug liking, euphoria) are similar between lisdexamfetamine and d-amphetamine, just delayed in onset 5
• Adderall immediate-release formulations have higher diversion risk, particularly in adolescents 1

Dosing Considerations

Vyvanse: 1

• Starting dose: 20-30 mg once daily in the morning
• Titration: Increase by 10 mg weekly
• Maximum: 70 mg daily

Adderall XR: 1

• Starting dose: 10 mg once daily in the morning
• Titration: Increase by 5 mg weekly
• Maximum: 50 mg daily

Side Effect Profile

• Both medications produce similar adverse effects including decreased appetite, sleep disturbances, increased blood pressure and heart rate, headaches, irritability, and stomach pain 1
• Both require monitoring of blood pressure, heart rate, weight, and height in children 1, 6
• Peak cardiovascular and subjective stimulant effects occur later with Vyvanse but reach similar magnitudes as Adderall 5

Special Populations

Pregnancy and Lactation

• Both medications have similar safety profiles in pregnancy with reassuring data regarding major congenital malformations 1
• Both carry possible small increased risks for gastroschisis, preeclampsia, and preterm birth when used in the second half of pregnancy 1
• Both are classified as Hale lactation risk category L3 1
• Limited published data exists specifically for lisdexamfetamine in pregnancy, but since it converts to dextroamphetamine, the amphetamine safety data applies 1

Adolescents at Risk for Diversion

• Vyvanse is preferred when diversion risk is a concern because the prodrug formulation makes extraction more difficult and provides no advantage when crushed or snorted 1
• Adderall immediate-release has higher diversion potential 1

Common Pitfalls

• Do not assume Vyvanse has dramatically lower abuse potential—while the prodrug design delays onset, oral administration produces similar peak subjective effects as d-amphetamine 5
• Both medications require the same cardiovascular monitoring—neither is safer regarding blood pressure or heart rate effects 1, 6, 5
• Do not use interchangeable dosing—Vyvanse doses are not equivalent to Adderall doses due to different salt formulations and the prodrug design 1