What is the difference between dextro-amphetamine and amphetamine salts (Adderall) in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy?

Dextroamphetamine vs Amphetamine Salts: Key Differences

Dextroamphetamine is the single, more potent enantiomer of amphetamine, while amphetamine salts (Adderall) contain a 3:1 ratio mixture of dextroamphetamine and levoamphetamine, providing a broader pharmacological profile with potentially different clinical effects.

Chemical Composition and Formulation

• Dextroamphetamine contains only the dextro (right-handed) enantiomer, specifically S-(+)-amphetamine, which is the more pharmacologically active form 1
• Amphetamine salts (Adderall) contain a racemic mixture with approximately 75% dextroamphetamine and 25% levoamphetamine [R-(-)-amphetamine], providing both enantiomers in a fixed ratio 2
• Both formulations are available as immediate-release and extended-release preparations, with similar dosing schedules of 2-3 times daily for immediate-release versions 1

Pharmacological Differences

• Both medications work by stimulating the release of norepinephrine and affecting α- and β-adrenergic receptor sites, but the enantiomer composition creates subtle differences in receptor binding profiles 3
• The levoamphetamine component in Adderall may contribute to more peripheral sympathomimetic effects (cardiovascular stimulation, appetite suppression) compared to pure dextroamphetamine 4
• Individual response to methylphenidate versus amphetamine is idiosyncratic, with approximately 40% responding to both and 40% responding to only one, though this applies to the amphetamine class generally rather than distinguishing between dextroamphetamine and mixed salts 5

Clinical Efficacy for ADHD

• Both medications demonstrate 70-80% response rates when properly titrated for adult ADHD treatment 5, 6
• Amphetamine-based stimulants (including both dextroamphetamine and mixed amphetamine salts) show superior efficacy compared to methylphenidate in adults, with larger effect sizes (SMD -0.79 vs -0.49) 5
• Low-quality evidence suggests amphetamines reduce ADHD symptom severity as rated by clinicians (SMD -0.90) and patients (SMD -0.51), though studies did not consistently distinguish between dextroamphetamine and mixed salts 7
• One small study found dextroamphetamine alone showed no evidence of reducing ADHD symptom severity (SMD -0.24), though this was very low-quality evidence from only 49 participants 7

Dosing Considerations

• Dextroamphetamine: typical adult dosing ranges from 5 mg three times daily to 20 mg twice daily, with standard recommended dosage of 5-60 mg daily 6, 1
• Amphetamine salts (Adderall): adult dosing ranges from 10-50 mg total daily dose, typically starting at 10 mg in the morning with titration by 5 mg weekly, with maximum doses reaching 40 mg for amphetamine salts 5, 6
• Effective responses to Adderall have been reported at relatively low doses (mean 10.77 mg/day or 0.14 mg/kg/day) in some adults with ADHD 8

Side Effect Profile

• Both medications share common adverse effects including appetite suppression, insomnia, anxiety, increased blood pressure and heart rate, and potential for abuse 1, 3
• Amphetamines typically cause greater effects on appetite and sleep due to longer excretion half-lives compared to methylphenidate 5
• Adderall may precipitate acute anxiety symptoms, particularly in patients with comorbid anxiety disorders (occurring in 4 of 7 patients with anxiety in one study) 8
• Both carry FDA black box warnings for high potential for abuse, misuse, and addiction, with risk of sudden death in patients with heart defects or serious heart disease 1

Compliance Monitoring

• The enantiomer composition difference allows for compliance monitoring in treatment programs: pure dextroamphetamine (Metamina) shows only S-(+)-amphetamine in testing, while street amphetamine or Adderall shows both enantiomers 2
• This distinction is particularly useful in patients with substance abuse history, where monitoring the ratio of R-(-)- to S-(+)-amphetamine in blood or hair can detect illicit use 2

Clinical Selection Criteria

• No definitive evidence supports choosing one over the other based on efficacy alone, as group studies generally fail to show significant differences between dextroamphetamine and mixed amphetamine salts 4
• Large individual differences in response to different drugs and doses exist, making the best choice for a particular patient unpredictable from published studies 4
• The choice between dextroamphetamine and amphetamine salts should be based on individual patient response during systematic titration, previous medication history, and specific comorbidities 4, 5
• For patients with prominent anxiety or cardiovascular concerns, starting with pure dextroamphetamine might theoretically reduce peripheral sympathomimetic effects, though this lacks strong evidence 8

Approved Indications

• Both medications are FDA-approved for narcolepsy and ADHD 1
• Dextroamphetamine is approved for ADHD in children ages 6-17 years, while paradoxically having approval for use in children as young as 3 years despite lacking published controlled safety and efficacy data 4, 1
• Both are DEA Schedule II controlled substances with high potential for abuse and require careful monitoring 1, 3