Lisdexamfetamine

Lisdexamfetamine, sold under the brand names Vyvanse (, VY-vans) and Elvanse among others, is a stimulant medication that is used as a treatment for attention deficit hyperactivity disorder (ADHD) in both children and adults, and for moderate-to-severe binge eating disorder in adults. A prodrug of dextroamphetamine, lisdexamfetamine is taken by mouth. Its effects generally begin within 90 minutes and last for up to 14 hours. Common side effects of lisdexamfetamine include loss of appetite, anxiety, diarrhea, trouble sleeping, irritability, and nausea. Rare but serious side effects include mania, sudden cardiac death in those with underlying heart problems, and psychosis. It has a high potential for substance abuse. Serotonin syndrome may occur if used with certain other medications. Its use during pregnancy may result in harm to the fetus, and use during breastfeeding is not recommended by the manufacturer as dextroamphetamine (its metabolite) can pass through the breastmilk. Lisdexamfetamine is an inactive prodrug that is formed by the condensation of L-lysine, a naturally occurring amino acid, and dextroamphetamine. In the blood, peptidase enzymes reverse this process to release the active agent, the central nervous system (CNS) stimulant dextroamphetamine. Lisdexamfetamine was approved for medical use in the United States in 2007 and in the European Union in 2012. In 2023, it was the 76th most commonly prescribed medication in the United States, with more than 9 million prescriptions. It is a Class B controlled substance in the United Kingdom, a Schedule 8 controlled drug in Australia, and a Schedule II controlled substance in the United States.

Uses

Medical

Lisdexamfetamine is used primarily as a treatment for attention deficit hyperactivity disorder (ADHD) and binge eating disorder. It has similar off-label uses as those of other pharmaceutical amphetamines, such as the treatment of narcolepsy. Individuals over the age of 65 were not commonly tested in clinical trials of lisdexamfetamine for ADHD. According to a 2019 systematic review, lisdexamfetamine was the most effective treatment for adult ADHD.

ADHD Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal dopamine system development or nerve damage, but, in humans with ADHD, long-term use of pharmaceutical amphetamines at therapeutic doses appears to improve brain development and nerve growth. Reviews of magnetic resonance imaging (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus of the basal ganglia. Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD. Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety. Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing quality of life and academic achievement, and producing improvements in a large number of functional outcomes across 9 categories of outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, service use (i.e., academic, occupational, health, financial, and legal services), and social function. Additionally, a 2024 meta-analytic systematic review reported moderate improvements in quality of life when amphetamine treatment is used for ADHD. One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5 IQ points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity. Another review indicated that, based upon the longest follow-up studies conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a substance use disorder as an adult. Models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems; these functional impairments involve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus to the prefrontal cortex. Stimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems. Approximately 80% of those who use these stimulants see improvements in ADHD symptoms. Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans. The Cochrane reviews on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse side effects. However, a 2025 meta-analytic systematic review of 113 randomized controlled trials found that stimulant medications were the only intervention with robust short-term efficacy, and were associated with lower all-cause treatment discontinuation rates than non-stimulant medications (e.g., atomoxetine). A Cochrane review on the treatment of ADHD in children with tic disorders such as Tourette syndrome indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine could exacerbate tics in some individuals.

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