Trial protocol of an open label pilot study of lisdexamfetamine for the treatment of acute methamphetamine withdrawal

Liam S Acheson; Nadine Ezard; Nicholas Lintzeris; Adrian Dunlop; Jonathan Brett; Craig Rodgers; Anthony Gill; Michael Christmass; Rebecca McKetin; Michael Farrell; Steve Shoptaw; Krista J Siefried

doi:10.1371/journal.pone.0275371

Trial protocol of an open label pilot study of lisdexamfetamine for the treatment of acute methamphetamine withdrawal

PLoS One. 2022 Oct 3;17(10):e0275371. doi: 10.1371/journal.pone.0275371. eCollection 2022.

Authors

Liam S Acheson^{1

2

3}, Nadine Ezard^{2

3

4}, Nicholas Lintzeris^{4

5

6}, Adrian Dunlop^{4

7

8}, Jonathan Brett^{9

10}, Craig Rodgers², Anthony Gill², Michael Christmass^{11

12}, Rebecca McKetin¹, Michael Farrell¹, Steve Shoptaw¹³, Krista J Siefried^{1

2

3}

Affiliations

¹ The National Drug and Alcohol Research Centre (NDARC), the University of New South Wales, Sydney, Australia.
² Alcohol and Drug Service, St Vincent's Hospital Sydney, Sydney, Australia.
³ The National Centre for Clinical Research on Emerging Drugs (NCCRED), c/o the University of New South Wales, Sydney, Australia.
⁴ New South Wales Drug and Alcohol Clinical Research and Improvement Network (DACRIN), Sydney, Australia.
⁵ The Langton Centre, South East Sydney Local Health District, Sydney, Australia.
⁶ Discipline of Addiction Medicine, the University of Sydney, Sydney, Australia.
⁷ Drug and Alcohol Clinical Services, Hunter New England Local Health District, Newcastle, Australia.
⁸ School of Medicine and Public Health, the University of Newcastle, Newcastle, Australia.
⁹ Clinical Pharmacology and Toxicology, St Vincent's Hospital Sydney, Sydney, Australia.
¹⁰ St. Vincent's Clinical School, the University of New South Wales, Sydney, Australia.
¹¹ Next Step Drug and Alcohol Services, Perth, Australia.
¹² National Drug Research Institute, Curtin University, Perth, Australia.
¹³ Department of Family Medicine, The University of California Los Angeles, Los Angeles, California, United States of America.

Abstract

Introduction: Methamphetamine (MA) use disorder is an important public health concern. MA withdrawal is often the first step in ceasing or reducing use. There are no evidence-based withdrawal treatments, and no medication is approved for the treatment of MA withdrawal. Lisdexamfetamine (LDX) dimesilate, used in the treatment of attention deficit hyperactivity disorder and binge eating disorder has the potential as an agonist therapy to ameliorate withdrawal symptoms, and improve outcomes for patients.

Methods: A single arm, open-label pilot study to test the safety and feasibility of LDX for the treatment of MA withdrawal. Participants will be inpatients in a drug and alcohol withdrawal unit, and will receive a tapering dose of LDX over five days: 250mg LDX on Day 1, reducing by 50mg per day to 50mg on Day 5. Optional inpatient Days 6 and 7 will allow for participants to transition to ongoing treatment. Participants will be followed-up on Days 14, 21 and 28. All participants will also receive standard inpatient withdrawal care. The primary outcomes are safety (measured by adverse events, changes in vital signs, changes in suicidality and psychosis) and feasibility (the time taken to enrol the sample, proportion of screen / pre-screen failures). Secondary outcomes are acceptability (treatment satisfaction questionnaire, medication adherence, concomitant medications, qualitative interviews), retention to protocol (proportion retained to primary and secondary endpoints), changes in withdrawal symptoms (Amphetamine Withdrawal Questionnaire) and craving for MA (visual analogue scale), and sleep outcomes (continuous actigraphy and daily sleep diary).

Discussion: This is the first study to assess lisdexamfetamine for the treatment of acute MA withdrawal. If safe and feasible results will go to informing the development of multi-centre randomised controlled trials to determine the efficacy of the intervention.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Alcoholism* / drug therapy
Amphetamine-Related Disorders* / drug therapy
Attention Deficit Disorder with Hyperactivity* / drug therapy
Central Nervous System Stimulants* / adverse effects
Double-Blind Method
Humans
Lisdexamfetamine Dimesylate / adverse effects
Methamphetamine* / adverse effects
Pilot Projects
Substance Withdrawal Syndrome* / drug therapy
Treatment Outcome

Substances

Central Nervous System Stimulants
Methamphetamine
Lisdexamfetamine Dimesylate

Grants and funding

This research was supported by internal funds from the National Centre for Clinical Research on Emerging Drugs (NCCRED). NCCRED is funded by the Australian Government Department of Health. The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.