From the Guidelines
Lisdexamfetamine is the preferred choice over dextroamphetamine for treating ADHD due to its lower abuse potential and longer duration of action, as evidenced by recent studies 1. When considering the treatment of ADHD, it's essential to weigh the benefits and risks of different medications. Lisdexamfetamine and dextroamphetamine are both stimulant medications, but they have distinct differences in their mechanism of action, duration, and potential for abuse.
- Lisdexamfetamine is a prodrug that is converted to dextroamphetamine in the body, which gives it a slower onset and longer duration of action (10-14 hours) compared to dextroamphetamine, which is immediately active and has a shorter duration (4-6 hours per dose) 1.
- The usual starting dose of lisdexamfetamine is 20-30 mg daily, which can be increased to a maximum of 70 mg daily, whereas dextroamphetamine typically starts at 5-10mg once or twice daily with a maximum of 40mg daily 1.
- Both medications can cause similar side effects, including decreased appetite, insomnia, increased heart rate, and anxiety, but lisdexamfetamine has a lower abuse potential due to its prodrug nature, making it less likely to cause a euphoric "high" if misused 2.
- Recent studies have shown that long-acting formulations like lisdexamfetamine are associated with better medication adherence and probably a lower risk of rebound effects, while short-acting formulations like dextroamphetamine allow for more flexibility with dosing frequency and titration 2.
- It's crucial to consider individual patient factors, such as specific symptoms, daily routine, history of substance use, and insurance coverage, when deciding between lisdexamfetamine and dextroamphetamine 1, 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 main difference between Lisdexamfetamine and Dexamphetamine is that Lisdexamfetamine is a prodrug of Dextroamphetamine, meaning it is converted into Dextroamphetamine in the body.
- Lisdexamfetamine does not have direct activity, but rather is metabolized into Dextroamphetamine, which then acts as a CNS stimulant.
- The pharmacokinetics of Dextroamphetamine are linear between 30 mg and 70 mg in pediatric patients and between 50 mg and 250 mg in adult patients after administration of Lisdexamfetamine 3. The exact therapeutic action of Lisdexamfetamine (and Dextroamphetamine) in ADHD and BED is not known.
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.
- The pharmacokinetics of lisdexamfetamine suggest a reduced potential for abuse compared to dexamphetamine, due to its rate-limited hydrolysis in the body 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 than d-amphetamine, but had similar maximal concentrations and total exposure 5.
- The subjective and cardiovascular stimulant effects of lisdexamfetamine also occurred later compared to d-amphetamine, but no differences in peak ratings of potentially abuse-related subjective drug effects were observed 5.
Efficacy and Safety of Lisdexamfetamine
- Lisdexamfetamine has been shown to be effective in improving symptoms associated with attention-deficit hyperactivity disorder (ADHD) in children aged 6-12 years 4.
- Lisdexamfetamine has also been approved for the treatment of moderate to severe binge eating disorder (BED) in adult patients, and has been shown to be effective in reducing binge eating days/week 6.
- The safety profile of lisdexamfetamine is similar to that of other amphetamine medications, with common adverse events including dry mouth, headache, and insomnia 4, 6.
Mechanism of Action of Lisdexamfetamine
- The exact mechanism of action of lisdexamfetamine is not fully understood, but it is thought to involve the release of pharmacologically active d-amphetamine, which acts on the central nervous system to improve symptoms of ADHD and BED 4, 7.
- Further studies are needed to fully understand the molecular mechanisms of lisdexamfetamine and its effects on ADHD and BED pathology 7.