From the Guidelines
Lisdexamfetamine is the preferred choice over dexamphetamine for treating ADHD due to its longer duration of action, smoother effect, and reduced potential for abuse, as evidenced by its prodrug nature that prevents alternative administration methods like snorting 1.
Key Differences Between Lisdexamfetamine and Dexamphetamine
- Lisdexamfetamine is a prodrug that must be metabolized in the bloodstream to become active, resulting in a longer duration of action (typically 10-14 hours) and a smoother effect with less potential for abuse.
- Dexamphetamine is immediately active when taken, resulting in faster onset (within 30 minutes) but shorter duration (3-5 hours per dose), often requiring multiple daily doses.
Dosage and Administration
- Dosing for lisdexamfetamine typically starts at 20-30 mg once daily and can be increased to 70 mg daily, as recommended by the American Journal of Obstetrics and Gynecology 1.
- Dexamphetamine usually starts at 5mg once or twice daily and can be increased as needed.
Considerations for Use
- Lisdexamfetamine may have fewer peaks and crashes throughout the day due to its prodrug nature, which can lead to a more stable therapeutic effect.
- The choice between these medications often depends on whether a patient needs longer-lasting coverage with fewer daily doses (lisdexamfetamine) or more flexible, shorter-acting treatment (dexamphetamine), with consideration of the patient's individual needs and medical history.
- As noted in a study on ADHD treatment, lisdexamfetamine is considered to have less abuse potential compared to other stimulant medications, making it a preferable option for patients at risk of substance abuse 2.
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.
- Lisdexamfetamine is a prodrug that is converted into dextroamphetamine in the body.
- The mechanism of action of lisdexamfetamine and dexamphetamine is the same, as lisdexamfetamine is a prodrug of dextroamphetamine.
- The pharmacological effects of lisdexamfetamine are due to its conversion to dextroamphetamine, which blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases the release of these monoamines into the extraneuronal space 3.
From the Research
Comparison of Lisdexamfetamine and Dexamphetamine
- Lisdexamfetamine is a prodrug of dextroamphetamine, which means it is converted into dextroamphetamine in the body 4.
- Dexamphetamine is the active form of the drug, responsible for its therapeutic effects 4.
- Lisdexamfetamine has a reduced potential for abuse due to its rate-limited hydrolysis, which gradually releases pharmacologically active d-amphetamine 4.
- A study comparing the pharmacokinetics and pharmacodynamics of lisdexamfetamine and d-amphetamine found that lisdexamfetamine had a longer lag time and reached peak levels later, but had similar maximal concentrations and total exposure 5.
Efficacy and Safety
- Lisdexamfetamine has been shown to be effective in improving symptoms of attention-deficit hyperactivity disorder (ADHD) in children and adults 4, 6.
- Dexamphetamine has also been shown to be effective in reducing the severity of ADHD symptoms, although the evidence is limited 6.
- Lisdexamfetamine has a good safety profile, with most adverse events being mild to moderate in severity 4, 7.
- Dexamphetamine has been associated with an increased risk of adverse events, including withdrawal due to adverse events 6.
Clinical Use
- Lisdexamfetamine is approved for the treatment of ADHD in children and adults, as well as for the treatment of binge eating disorder in adults 4, 7.
- Dexamphetamine is also used to treat ADHD, although its use is not as well established as lisdexamfetamine 6.
- The choice between lisdexamfetamine and dexamphetamine may depend on individual patient needs and circumstances, as well as the specific clinical situation 8.