Why doesn't Vyvanse (lisdexamfetamine) have the same effect as Adderall (amphetamine and dextroamphetamine) for me?

Why Vyvanse Feels Different from Adderall

Vyvanse (lisdexamfetamine) feels different from Adderall because it is a prodrug that requires enzymatic conversion in the bloodstream, resulting in a more gradual onset, smoother effect profile, and longer duration of action compared to Adderall's more immediate and potentially more intense effects.

Pharmacological Differences

Mechanism of Action

• Vyvanse (lisdexamfetamine):

  • Is a prodrug that requires enzymatic hydrolysis in the bloodstream to convert to active dextroamphetamine 1
  • This conversion occurs primarily in red blood cells after oral administration 1
  • The inactive lisdexamfetamine molecule must be cleaved to release the active d-amphetamine 2

• Adderall (mixed amphetamine salts):

  • Contains immediately available amphetamine and dextroamphetamine salts
  • Begins working more quickly as it doesn't require conversion

Pharmacokinetic Differences

1. Onset of Action:

   • Vyvanse has approximately 0.6 ± 0.6 hours longer lag time before effects begin 3
   • Peak plasma levels are reached about 1.1 ± 1.5 hours later with Vyvanse compared to immediate-release dextroamphetamine 3

2. Duration of Effect:

   • Vyvanse provides consistent effects for approximately 13 hours in children and 14 hours in adults 4
   • The plasma elimination half-life of lisdexamfetamine is less than one hour, while the resulting dextroamphetamine has a half-life of 10-11.3 hours in adults 1

3. Consistency of Effect:

   • Vyvanse was specifically developed to provide extended duration with consistent effects throughout the day 4
   • The enzymatic conversion process creates more predictable blood levels compared to immediate-release formulations 2

Subjective Experience Differences

Why You Might Feel Different Effects

1. Smoother Onset:

   • The gradual conversion of Vyvanse to active dextroamphetamine results in a smoother onset of effects
   • This contrasts with Adderall's potentially more abrupt onset, which some patients experience as a more noticeable "kick in" 3

2. Less Pronounced Peaks and Valleys:

   • Vyvanse tends to produce more consistent plasma concentrations throughout the day 4
   • Adderall, especially immediate-release formulations, may create more noticeable fluctuations in effect

3. Different Amphetamine Composition:

   • Vyvanse converts solely to dextroamphetamine
   • Adderall contains a mixture of dextroamphetamine and levoamphetamine salts, which may produce slightly different subjective effects

Clinical Implications

Efficacy Considerations

• Both medications are effective for ADHD treatment, with comparable clinical efficacy when dosed appropriately 5
• In a crossover study, both Vyvanse and mixed amphetamine salts immediate-release had significant effects on ADHD ratings with response rates of about 80% 5

Dosing Differences

• Vyvanse is taken once daily due to its extended-release profile
• Adderall immediate-release typically requires multiple daily doses (often 2-3 times per day) to maintain effects throughout the day

Individual Variability

• Individual metabolism differences can significantly affect how each medication works for you
• Some patients respond better to one formulation than another despite their similar active ingredients

Practical Considerations

When to Consider Switching

• If you experience uncomfortable peaks and valleys with Adderall
• If multiple daily dosing is inconvenient
• If you need longer duration of coverage throughout the day

When to Discuss with Your Doctor

• If you feel Vyvanse is not providing adequate symptom control
• If you experience different side effects with one medication versus the other
• If the timing of effects doesn't align with your daily needs

Conclusion

The difference in how Vyvanse feels compared to Adderall is primarily due to its prodrug formulation, which creates a more gradual onset and consistent effect profile. While both medications ultimately deliver amphetamine to the brain, the delivery method significantly impacts the subjective experience. Discussing these differences with your healthcare provider can help determine which medication best suits your specific needs.