From the Guidelines
Vyvanse (lisdexamfetamine) does not increase dopamine levels in the brain similarly to Adderall (amphetamine and dextroamphetamine), as it is a prodrug that requires metabolism to convert to dextroamphetamine, resulting in a smoother and more gradual onset of action. This is supported by the fact that Vyvanse must first be metabolized in the bloodstream to convert to dextroamphetamine, which then gradually increases dopamine levels 1. In contrast, Adderall contains immediate-release amphetamine salts that cause a more rapid dopamine increase. The conversion process of Vyvanse takes time, as it requires enzymes in red blood cells to cleave the lysine molecule from lisdexamfetamine, creating a more controlled release of the active ingredient 1.
Some key points to consider when comparing Vyvanse and Adderall include:
- Both medications ultimately work by increasing dopamine and norepinephrine in the brain to improve focus and attention 1
- Vyvanse's gradual release mechanism typically provides more consistent effects over 10-14 hours with fewer ups and downs than Adderall's more immediate impact 1
- The metabolic process of Vyvanse cannot be accelerated by crushing or snorting the medication, giving it a lower potential for abuse compared to Adderall 1
- Stimulant medications, including Vyvanse and Adderall, are associated with a range of adverse effects, including decreased appetite, sleep disturbances, and increased blood pressure and pulse 1
It is essential to consider the unique pharmacological profiles of Vyvanse and Adderall when selecting a treatment for ADHD, as well as the potential risks and benefits associated with each medication 1. The most recent and highest quality study suggests that Vyvanse's gradual release mechanism provides a smoother and more consistent onset of action compared to Adderall 1.
From the FDA Drug Label
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action Lisdexamfetamine is a prodrug of dextroamphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The exact mode of therapeutic action in ADHD and BED is not known. 12. 2 Pharmacodynamics Amphetamines block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.
- Key Points:
- Lisdexamfetamine is a prodrug of dextroamphetamine.
- Amphetamines, including dextroamphetamine, increase dopamine levels by blocking reuptake and increasing release.
- Comparison to Adderall:
- Since both Vyvanse (lisdexamfetamine) and Adderall (amphetamine and dextroamphetamine) are amphetamines, they increase dopamine levels in a similar manner, through blocking reuptake and increasing release.
- Clinical Decision:
- Based on the mechanism of action, Vyvanse (lisdexamfetamine) is expected to increase dopamine levels in the brain similarly to Adderall (amphetamine and dextroamphetamine) 2.
From the Research
Mechanism of Action
- Lisdexamfetamine, the active ingredient in Vyvanse, is a prodrug that is hydrolyzed to its active form d-amphetamine in the blood following oral administration 3.
- D-amphetamine competitively inhibits the dopamine transporter (DAT) and the noradrenaline transporter (NAT) to increase dopamine (DA) and noradrenaline (NA) concentrations in the synaptic cleft 3.
- Amphetamines, including d-amphetamine, act by increasing presynaptic release of dopamine and other biogenic amines in the brain 4.
Comparison with Adderall
- Adderall is a combination of amphetamine and dextroamphetamine, which also increase dopamine levels in the brain by inhibiting the reuptake of dopamine and promoting its release 4.
- Lisdexamfetamine produces smaller, but more sustained, increases in striatal dopamine efflux than immediate-release d-amphetamine 5.
- The pharmacokinetic/pharmacodynamic relationships of lisdexamfetamine and immediate-release d-amphetamine differ, with lisdexamfetamine producing an identical AUC for plasma d-amphetamine, but a 50% lower C(max) and significantly delayed t(max) 5.
Effects on Dopamine Levels
- Lisdexamfetamine increases dopamine levels in the brain, but with a more sustained effect compared to immediate-release d-amphetamine 5.
- The increase in dopamine levels is associated with the therapeutic effect of lisdexamfetamine in attention-deficit/hyperactivity disorder (ADHD) 3, 4.
- Long-term treatment with stimulants, including methylphenidate, can affect brain dopamine transporter levels, which may impact treatment efficacy 6.