Differences Between Adderall, Vyvanse, and Dexedrine
All three medications are amphetamine-based stimulants approved for ADHD and narcolepsy, but they differ fundamentally in their active ingredients, pharmacokinetics, and duration of action. 1, 2, 3
Active Ingredients
Dexedrine (dextroamphetamine): Contains only the dextro-isomer of amphetamine, which is the pharmacologically active component 1, 2
Adderall (mixed amphetamine salts): Contains a 3:1 ratio of dextroamphetamine to levoamphetamine, providing a combination of both amphetamine isomers 4, 5
Vyvanse (lisdexamfetamine): A prodrug consisting of dextroamphetamine covalently bonded to L-lysine, which is therapeutically inactive until enzymatically hydrolyzed in the body to release active dextroamphetamine 3, 6
Duration of Action
Dexedrine immediate-release: Requires dosing every 4-6 hours with peak effects within 1-3 hours and a half-life of approximately 2 hours 7, 1
Adderall immediate-release: Similar short-acting profile requiring multiple daily doses at 4-6 hour intervals 1, 4
Vyvanse: Provides extended duration through rate-limited enzymatic conversion, with gradual release of dextroamphetamine throughout the day, typically lasting 10-13 hours 8, 3
Side Effect and Safety Profiles
Common Side Effects (All Three Medications)
Agitation, tachycardia, hyperthermia, tremors, insomnia, and anorexia are the most frequently reported adverse effects across all amphetamine formulations 4, 5, 6
Cardiovascular effects including increased heart rate, blood pressure, and stroke volume occur through α- and β-adrenergic receptor stimulation 4
Abuse Potential Differences
Vyvanse has significantly lower abuse potential compared to both immediate-release and extended-release dextroamphetamine/amphetamine formulations 6
The odds of abuse/misuse for immediate-release dextroamphetamine/amphetamine (Adderall IR) are 2.3 times higher than lisdexamfetamine 6
Extended-release dextroamphetamine/amphetamine (Adderall XR) has 1.9 times higher odds of abuse/misuse compared to lisdexamfetamine 6
The prodrug design of Vyvanse reduces likability in stimulant abusers, as the medication requires enzymatic hydrolysis and cannot be rapidly absorbed through alternative routes of administration 3
Serious Outcomes
Moderate to major adverse outcomes occurred in 21.2% of lisdexamfetamine exposures, 24.7% of extended-release amphetamine exposures, and 25.5% of immediate-release amphetamine exposures reported to poison centers 6
All amphetamine formulations can cause seizures (managed with benzodiazepines, phenothiazines, or propofol) and cardiac tachyarrhythmias (managed with β-blockers like propranolol) in overdose situations 4
Dosing Considerations
Dexedrine: Starting dose 5 mg daily for children 6-12 years (2.5 mg for ages 3-5), titrated in 5 mg increments weekly; adults start at 10 mg daily 1, 2
Adderall: Similar dosing to Dexedrine, with 5 mg once or twice daily for children ≥6 years, rarely exceeding 40 mg/day total 1
Vyvanse: Typically dosed 30-70 mg once daily, with dose adjustments in 10-20 mg increments weekly 8, 5
Clinical Efficacy
All three medications demonstrate efficacy in reducing ADHD symptom severity as rated by clinicians and patients 5
Lisdexamfetamine showed the strongest effect size (SMD -1.06) compared to mixed amphetamine salts (SMD -0.80) in reducing clinician-rated ADHD symptoms 5
Individual response to specific amphetamine formulations is unpredictable, and sequential trials of different stimulants may be necessary, with over 90% of patients responding to one formulation when both are tried 7
Key Clinical Pitfall
The extended duration of Vyvanse cannot be further extended by increasing the dose—if symptom coverage is inadequate in late afternoon/evening, adding a short-acting dextroamphetamine or mixed amphetamine salt booster (5-10 mg) in early-to-mid afternoon is the recommended strategy rather than escalating the Vyvanse dose beyond therapeutic range 8