Lisdexamfetamine: chemistry, pharmacodynamics, pharmacokinetics, and clinical efficacy, safety, and tolerability in the treatment of binge eating disorder

  title={Lisdexamfetamine: chemistry, pharmacodynamics, pharmacokinetics, and clinical efficacy, safety, and tolerability in the treatment of binge eating disorder},
  author={Kristen M. Ward and Leslie Citrome},
  journal={Expert Opinion on Drug Metabolism \& Toxicology},
  pages={229 - 238}
  • Kristen M. Ward, L. Citrome
  • Published 4 January 2018
  • Medicine, Biology, Psychology
  • Expert Opinion on Drug Metabolism & Toxicology
ABSTRACT Introduction: The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval… 
Effects of Lisdexamfetamine, a Prodrug of D-Amphetamine, on Locomotion, Spatial Cognitive Processing and Neurochemical Profiles in Rats: A Comparison With Immediate-Release Amphetamine
Results suggest that lisdexamfetamine was more effective than d-amphetamine in improving spatial cognitive performance, which was attributed to the steady and lasting dopamine release pattern within the mPFC.
Drugs alone or in combination approaches may be useful pharmacotherapies to yield promising outcomes acutely and over longerterm follow-up in the treatment of BED.
Clinical and Biological Perspectives of Non-antipsychotic Psychotropic Medications and Weight Gain
Unlike antipsychotic medications, non-antipsychotic psychotropic drugs cause the least weight gain mediated by multiple mechanisms, but mostly without meeting salient features of metabolic syndrome.
Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge eating disorder
Investigation of the anti-binge effects of OEA in a rat model of binge-like eating provides evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge, like eating behavior.
Binge-Eating Disorder and Type 2 Diabetes: A Review.
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  • Medicine, Psychology
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  • 2020
Preclinical Models of Stress and Environmental Influences on Binge Eating
Animal studies have revealed the involvement of different neurotransmitter pathways, especially dopamine, opioids, CRF, serotonin, orexin, and GABAergic systems in binge-like eating, and may aid in the ultimate goal of identifying novel, safe, and effective therapeutic targets.
Trace amine–associated receptor 1 (TAAR1) promotes anti-diabetic signaling in insulin-secreting cells
TAAR1 is coupled to Gαs-signaling pathways in insulin-secreting β-cells to cause protein kinase A (PKA)/exchange protein activated by cAMP (Epac)–dependent release of insulin, activation of RAF proto-oncogene, Ser/Thr kinase (Raf), Raf, and MAPK/ERK kinase 1/2 (MEK1/2).
Binge eating disorder revisited: what’s new, what’s different, what’s next
Routine medication treatments for anxiety and depression do not necessarily ameliorate the symptoms of BED, but there are approved and emerging medication options that specifically address the core drivers behind binge eating, namely obsessive thoughts and compulsive behaviors regarding food, resulting in marked decreases in binge eating behaviors as well as weight loss.


Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects
The pharmacokinetics and pharmacodynamics of lisdexamfetamine are similar to D-amphetamine administered 1h later, and are likely associated with a similar risk of oral abuse as D- methamphetamine.
Lisdexamfetamine: A pharmacokinetic review.
Amphetamine, past and present – a pharmacological and clinical perspective
The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults.
Pharmacokinetic and Pharmacodynamic Properties of Lisdexamfetamine in Adults with Attention-Deficit/Hyperactivity Disorder.
Prodrug LDX levels peaked fairly rapidly and declined, while d-amphetamine levels peaked 3 hours later thanLDX levels and persisted throughout the day and the absence of PK/PD correlations between PK data and TASS ratings may be due to the subjects being tested in a controlled nonattention demanding environment.
Metabolism, Distribution and Elimination of Lisdexamfetamine Dimesylate
Lisdexamfetamine dimesylate was quickly absorbed, extensively metabolized to d-amphetamine and its derivatives, and rapidly eliminated following a single 70 mg oral dose in normal, healthy adult subjects.
Effects of Omeprazole on the Pharmacokinetic Profiles of Lisdexamfetamine Dimesylate and Extended-Release Mixed Amphetamine Salts in Adults
Nearly 50% of subjects receiving MAS XR showed an earlier Tmax while on omeprazole, indicating unpredictable release of active drug by the second bead ofMAS XR, most likely related to reduced stomach acid while on a PPI compromising the pulsed delivery of MASXR.
Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers
LDX administered intravenously did not produce significant subjective abuse-related liking scores at assessed doses, and was well tolerated in this population of adult substance abusers.
Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge-eating disorder: a randomized clinical trial.
The 50- and 70-mg/d treatment groups demonstrated efficacy compared with the placebo group in decreased BE days, BE cessation, and global improvement in a randomized, double-blind, parallel-group, forced dose titration, placebo-controlled clinical trial.
Lisdexamfetamine Dimesylate Effects on the Pharmacokinetics of Cytochrome P450 Substrates in Healthy Adults in an Open-Label, Randomized, Crossover Study
LDX did not alter CYP1A2, CYP2D6, or CYP3A activity and parent/metabolite Cmax and AUC0–∞ ratios were similar between treatments except for dextromethorphan/dextrorphan A UC0-∞ ratio, which was lower with LDX.