What is the comparison between Vyvanse (lisdexamfetamine) and Adderall (amphetamine/dextroamphetamine) for treating Attention Deficit Hyperactivity Disorder (ADHD)?

Vyvanse vs. Adderall for ADHD Treatment

Lisdexamfetamine (Vyvanse) is preferred over Adderall for ADHD treatment due to its lower abuse potential, more consistent therapeutic effect, and once-daily dosing convenience, while maintaining similar efficacy. 1, 2

Mechanism of Action and Pharmacokinetics

Both medications are amphetamine-based stimulants that work by:

• Blocking reuptake of norepinephrine and dopamine
• Increasing release of these monoamines into the extraneuronal space 2

Key differences:

• Vyvanse (Lisdexamfetamine):

  • Prodrug requiring enzymatic conversion to active dextroamphetamine
  • Primarily metabolized in the bloodstream by red blood cells 2
  • Longer time to peak concentration (approximately 4.4 hours) 2
  • More consistent therapeutic effect throughout the day
  • Cannot be effectively abused through snorting or injection 3

• Adderall (Mixed amphetamine salts):

  • Directly active medication
  • More rapid onset of action
  • Shorter duration requiring multiple daily doses (for immediate-release)
  • Higher potential for abuse

Efficacy Comparison

Both medications are considered first-line treatments for ADHD with:

• Response rates of 70-90% 1
• Clinically significant improvements in ADHD symptoms 1

In head-to-head comparison:

• Lisdexamfetamine demonstrated faster and more robust treatment response compared to non-stimulant atomoxetine in patients who previously responded inadequately to methylphenidate 4
• While direct head-to-head studies between Vyvanse and Adderall are limited, both show similar efficacy profiles for ADHD symptom reduction

Safety and Side Effect Profile

Common side effects for both medications include:

• Decreased appetite
• Insomnia
• Weight loss
• Increased blood pressure and heart rate 1

Important distinctions:

• Lisdexamfetamine has higher rates of decreased appetite, insomnia, and weight loss compared to methylphenidate 1
• Amphetamine derivatives (including both medications) have greater association with psychosis and psychotic disorders than methylphenidate 1
• Adderall may have higher addiction potential compared to Vyvanse due to its direct activity 1, 3

Abuse Potential

• Vyvanse: Lower abuse potential due to prodrug formulation requiring enzymatic activation, making it ineffective when snorted or injected 3, 5
• Adderall: Higher potential for misuse and diversion, particularly in adolescent and young adult populations 3

Dosing Considerations

• Vyvanse: Once-daily dosing (typical starting dose 30mg, maximum 70mg) 2
• Adderall: Typically requires multiple daily doses for immediate-release formulation (starting dose 5-10mg daily, maximum 50mg daily) 1

Clinical Recommendations

1. Initial Assessment:

   • Screen for contraindications including cardiovascular disease, high blood pressure, hyperthyroidism, glaucoma, agitation, history of substance abuse, psychosis, or mania 1
   • Evaluate baseline vital signs, weight, and psychiatric symptoms

2. Medication Selection:

   • For patients with concerns about medication adherence: Choose Vyvanse for once-daily dosing
   • For patients with history or risk of substance abuse: Vyvanse is preferred due to lower abuse potential 5
   • For patients requiring immediate symptom control: Consider Adderall for faster onset

3. Monitoring:

   • Weekly contact during initial titration
   • Regular monitoring of vital signs, weight, appetite, and height
   • Assess for emergence of psychiatric symptoms
   • Administer medication early in the day to minimize sleep disruption 1

Important Caveats

• Approximately 40% of patients respond to both methylphenidate and amphetamine, while 40% respond to only one 1
• Effects cease when medication stops, requiring consistent treatment 1
• Both medications are controlled substances (CII) requiring careful prescribing and monitoring 2
• Combination with behavioral interventions is recommended for optimal outcomes 1

In summary, while both medications are effective for ADHD treatment, Vyvanse offers advantages in terms of once-daily dosing, reduced abuse potential, and more consistent therapeutic effect, making it generally preferable for most patients when cost is not a limiting factor.