Multidimensional Evaluation of Lisdexamfetamine: Pharmacology, Therapeutic Use, Toxicity and Forensic Implications

Basic Clin Pharmacol Toxicol. 2025 Nov;137(5):e70111. doi: 10.1111/bcpt.70111.

Abstract

Lisdexamfetamine (LDX), a prodrug of d-amphetamine, is widely used in the pharmacological treatment of neuropsychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and binge eating disorder (BED). Chemically, it consists of the amino acid lysine linked to d-amphetamine. Its enzymatic conversion to d-amphetamine sets the stage for a prolonged and controlled release, influencing its clinical profile and differentiating it from other stimulant medications. As a central nervous system stimulant, LDX primarily acts by increasing the release of neurotransmitters, particularly dopamine and noradrenaline, in the brain. Clinically, this enhanced availability of neurotransmitters is believed to contribute to improvements in attention, focus and impulse control in individuals with ADHD. The side effects of LDX include insomnia, decreased appetite, weight loss and xerostomia. This work reviews the pharmacological mechanisms, clinical applications and forensic considerations associated with its use. It is expected that clinicians, researchers and policymakers have a comprehensive understanding of the pharmacological and toxicological aspects of LDX.

Keywords: attention‐deficit/hyperactivity disorder; d‐amphetamine; lisdexamfetamine; pharmacodynamics; pharmacokinetics.

Publication types

  • Review

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity* / drug therapy
  • Binge-Eating Disorder / drug therapy
  • Central Nervous System Stimulants* / adverse effects
  • Central Nervous System Stimulants* / pharmacokinetics
  • Central Nervous System Stimulants* / pharmacology
  • Central Nervous System Stimulants* / therapeutic use
  • Humans
  • Lisdexamfetamine Dimesylate* / adverse effects
  • Lisdexamfetamine Dimesylate* / pharmacokinetics
  • Lisdexamfetamine Dimesylate* / pharmacology
  • Lisdexamfetamine Dimesylate* / therapeutic use
  • Prodrugs / adverse effects
  • Prodrugs / pharmacology
  • Prodrugs / therapeutic use

Substances

  • Lisdexamfetamine Dimesylate
  • Central Nervous System Stimulants
  • Prodrugs