Lisdexamfetamine: A prodrug for the treatment of attention-deficit/hyperactivity disorder
Abstract
Purpose The pharmacology, pharmacokinetics, indications, clinical efficacy, adverse effects, drug interactions, dosage, and administration of lisdexamfetamine are reviewed. Summary Lisdexamfetamine is the first prodrug formulation of the stimulant dextroamphetamine. It is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children age 6-12 years and adults. Due to the need for enzymatic hydrolysis, there is a decreased liability for misuse and diversion with lisdexamfetamine. Moreover, due to the rate-limiting nature of hydrolysis, the toxicity potential and chances of overdose with lisdexamfetamine are reduced. The recommended starting dosage of lisdexamfetamine is 30 mg orally daily, which can be adjusted to a maximum dosage of 70 mg daily. Clinical trials in children age 6-12 years with ADHD found significant reductions in the ADHD symptoms with lisdexamfetamine compared with placebo. However, clinical studies in adolescents have not been conducted. The efficacy and safety of lisdexamfetamine in children with ADHD and comorbid psychiatric disorders also remain to be assessed. A controlled trial in adults similarly showed significant improvements in ADHD symptoms in all treatment groups. Long-term clinical trials and head-to-head comparison trials with existing stimulant formulations are necessary. The most common adverse effects include decreased appetite, insomnia, irritability, dizziness, and weight loss. Conclusion Clinical trials in childr…
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LDX inhibits the activity of SERT and MAO, not shared with MPH.
“LDX inhibits the activity of two other important proteins, not shared with MPH, involved in the monoaminergic system described in ADHD: SERT [164] and MAO [165].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [165]
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Quintero, J., Gutiérrez-Casares, J. R., & Álamo, C. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00392-2 · Cited by 70 · see citing works
“LDX regulates more receptors (TAAR1, VMAT2, SERT, MAOA and MAOB) than MPH in neurotransmission, and minimal differences, such as ERK2 phosphorylation and the action on locus coeruleus neurons by LDX, could differentiate efficacy between both drugs.”
BackgroundInfluential
- Authors
- Popovic, B., Bhattacharya, P., & Sivaswamy, L.
- Affiliations
- NewYork–Presbyterian Hospital (US)
- Wayne State University (US)
- Corresponding author
- Popovic, Biljana
- Venue
- American Journal of Health-System Pharmacy
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-11-15
- Volume
- 66
- Issue
- 22
- Pages
- 2005-2012
- ISSN
- 1079-2082 (ISSN-L)
- 1535-2900
- OpenAlex
- W2090095267
- Cited by
- 24
- References
- 6
- Citations by year
- 2026: 3 · 2025: 1 · 2023: 3 · 2022: 2 · 2019: 1 · 2016: 1 · 2014: 4 · 2012: 3
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Health-System Pharmacy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- lisdexamfetamine, prodrugs, attention deficit hyperactivity disorder, d-amphetamine, stimulant medication, pharmacokinetics, drug interactions, adverse effects, abuse liability, children with ADHD, adult ADHD, psychiatric comorbidity, dosage and administration
- MeSH terms
- Lisdexamfetamine Dimesylate, Adult, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Clinical Trials as Topic, Dextroamphetamine, Dose-Response Relationship, Drug, Drug Interactions, Humans, Prodrugs, Psychiatric Status Rating Scales
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