What is the potential for abuse of lisdexamfetamine in adults? A preclinical and clinical literature review and expert opinion

ABSTRACT

Introduction

Lisdexamfetamine dimesylate (LDX) is a prodrug approved for attention deficit/hyperactivity disorder and for moderate-to-severe binge eating disorder in adults in some countries.

Area covered

We aimed to specify the abuse potential of LDX in adults, using a review of pharmacokinetic/pharmacodynamic (PK/PD), animal, clinical, and pharmaco-epidemiological studies, through a PubMed search since inception until May 2021 using the following keywords: “lisdexamfetamine AND (‘misuse’ OR ‘abuse’ OR ‘diversion’ OR ‘addiction’)”.

Expert opinion

Most of the studies highlighted a longer T_max than dexamphetamine leading to a delayed onset of effects and a decreased C_max. These PK parameters were often associated with a diminished feeling of euphoria, in comparison to immediate-release dexamphetamine. The potential for abuse was also limited by the prodrug property of LDX, thus reducing the risk of misuse. Nevertheless, all the data were not convergent, as some authors reported similar C_max for LDX and dexamphetamine and reinforcing properties with a dose-dependent effect. Epidemiological studies found that abuse rates of LDX were substantially lower than those of immediate-release dexamphetamine. Overall, although LDX abuse seems possible, we did not find evidence concerning current safety signal. However, more long-term pharmaco-epidemiological studies are still needed to confirm this finding.

KEYWORDS:

• Abuse
• attention deficit hyperactivity disorder
• misuse
• lisdexamfetamine
• safety

Article highlights

• The pharmacokinetic profile of LDX was generally in favor of a lower abuse potential, relative to that of dexamphetamine

• All the data were not convergent, as some authors reported similar C_max for LDX and dexamphetamine and dose-dependent reinforcing properties

• Epidemiological studies found that abuse rates of LDX were lower than those of immediate-release dexamphetamine

• The potential for abuse of LDX may be underestimated by the lack of available data

• Post-marketing surveillance, through pharmaco-epidemiological studies and pharmacovigilance/addictovigilance data are essential to further document this risk

Declaration of interest

S Weibel has received congress invitation and travel expenses from Janssen and UCB Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed being part of an osteoarthritis team supported by Pfizer and Eli Lilly (2019-2021). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.