Lisdexamfetamine
A prodrug of dexamfetamine (Vyvanse) that is inactive until metabolised, giving a smoother onset and lower abuse liability than immediate-release amphetamine. Approved for ADHD and binge-eating disorder. Retains amphetamine's dependence, cardiovascular and appetite/sleep trade-offs.
01 Overview
Lisdexamfetamine is L-lysine covalently bound to dextroamphetamine. It is pharmacologically inactive until enzymatically cleaved (mainly in red blood cells), releasing dexamfetamine gradually. This design gives a long, smooth duration and reduces the euphoric peak from snorting or injecting, lowering but not eliminating abuse potential.
It is approved for ADHD in children and adults and for moderate-to-severe binge-eating disorder. Because the active moiety is dexamfetamine, its side-effect profile mirrors amphetamine: appetite suppression, insomnia, raised heart rate and blood pressure, and dependence potential (Schedule II).
02 Mechanism
Prodrug hydrolysed to active dextroamphetamine, which displaces and blocks reuptake of dopamine and noradrenaline, raising synaptic catecholamines.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Therapeutic (ADHD) | 30–70 mg/day | Oral | Once daily in the morning; titrated from 30 mg. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved attention and impulse controlEfficacious across the day with a single morning dose in controlled trials. | Large effect size in ADHD | Clinical | |
| Reduced binge-eating episodesFDA-approved for binge-eating disorder based on reduced binge days in trials. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Appetite suppression and weight lossDecreased appetite is among the most common adverse effects. | Moderate | Very common | Clinical | |
| InsomniaDifficulty sleeping, especially with later dosing. | Moderate | Common | Clinical | |
| Dependence and cardiovascular stimulationRaised heart rate/blood pressure and abuse potential inherent to amphetamines. | Moderate | Common | Clinical |