What is the preferred medication between Dexedrine (dextroamphetamine) and Vyvanse (lisdexamfetamine) for a patient with Attention Deficit Hyperactivity Disorder (ADHD)?

Vyvanse vs Dexedrine for ADHD Treatment

Vyvanse (lisdexamfetamine) is the preferred medication over Dexedrine (dextroamphetamine) for most patients with ADHD, particularly adolescents and young adults, due to its significantly lower abuse potential, once-daily dosing that improves adherence, and consistent all-day symptom coverage lasting 13-14 hours. 1, 2, 3

Key Pharmacological Differences

Vyvanse is a prodrug that requires enzymatic conversion in red blood cells to become active dextroamphetamine, making it therapeutically inactive until metabolized in the body. 1, 2 This unique mechanism means it cannot produce high dextroamphetamine levels when crushed, injected, or snorted, resulting in substantially lower abuse-related drug-liking scores compared to immediate-release dextroamphetamine at equivalent doses. 4, 2

Dexedrine is immediate-release dextroamphetamine that is active upon ingestion, requiring multiple daily doses (typically 5 mg three times daily to 20 mg twice daily) to maintain therapeutic effect throughout the day. 5

Clinical Efficacy

• Both medications demonstrate equivalent efficacy for core ADHD symptoms when dosed appropriately, with response rates of approximately 70% for either medication as monotherapy. 1
• Nearly 90% of patients respond to either medication if both are tried sequentially. 1
• Vyvanse provides consistent efficacy for a full treatment day, up through 6 PM, based on parent ratings in morning, afternoon, and early evening assessments (all P < 0.001 vs placebo). 2
• Clinical trials demonstrate significant improvements in ADHD Rating Scale Version IV scores with Vyvanse, with improvements noted within the first week of treatment. 2

Dosing Algorithms

Vyvanse Dosing

• Start at 20-30 mg once daily in the morning 1
• Increase by 10 mg weekly based on symptom response 1
• Maximum dose: 70 mg daily 1
• Duration of action: 13 hours in children, 14 hours in adults 2, 3

Dexedrine Dosing

• Start at 5 mg three times daily 5
• Titrate to 5-20 mg three times daily or 20 mg twice daily 5
• Maximum dose: 60 mg daily 5
• Requires multiple daily doses for sustained effect 5

Critical Clinical Advantages of Vyvanse

The American Academy of Pediatrics explicitly recommends Vyvanse over immediate-release amphetamines in adolescents and young adults specifically because of concerns about diversion and abuse. 1 This is critically important in college-age patients who face significant peer pressure for stimulant diversion. 1

Vyvanse's once-daily dosing improves medication adherence compared to multiple daily doses required with Dexedrine. 5 This is particularly valuable for patients who struggle with remembering multiple doses throughout the day.

Vyvanse follows linear pharmacokinetics at therapeutic doses (30-70 mg), providing consistent plasma concentrations throughout the day. 2, 3

Special Population: Stimulant Use Disorder

Vyvanse is a feasible treatment option for patients with ADHD and a history of stimulant use disorder. 6 A case report demonstrated successful treatment with lisdexamfetamine 40 mg in a patient with methamphetamine use disorder, showing not only improvement in ADHD symptoms but also significant decrease in cravings for stimulants, with no illicit substance use confirmed by routine urine drug screens. 6

Due to its unique pharmacokinetic profile as a prodrug, lisdexamfetamine has lower abuse potential compared to conventional stimulants like Dexedrine. 4, 6

Safety Profile

The most common adverse events with Vyvanse are typical of amphetamine products and include decreased appetite, insomnia, upper abdominal pain, headache, irritability, weight loss, and nausea. 2 These are generally mild to moderate in intensity and transient in nature. 3

Both medications carry similar cardiovascular monitoring requirements: blood pressure and pulse must be monitored at baseline and regularly during treatment. 5

Common Pitfalls to Avoid

• Do not assume both medications are interchangeable—the abuse potential difference is clinically significant, especially in adolescents and young adults. 1
• Do not prescribe immediate-release formulations like Dexedrine when extended-release options like Vyvanse are available, as they have higher abuse potential. 1
• Do not ignore the social context—college-age patients face significant peer pressure for stimulant diversion, making Vyvanse's abuse-deterrent properties particularly valuable. 1
• Screen for substance abuse symptoms before initiating treatment and monitor prescription-refill requests for signs of misuse or diversion. 1

When to Consider Dexedrine

Dexedrine may be appropriate when flexible dosing throughout the day is needed or when immediate-release formulation is required for initial titration or specific timing needs. 1 However, this represents a minority of clinical scenarios, and Vyvanse remains the preferred first-line option for most patients with ADHD.