Randomized Controlled Trial

. 2025 Jul;120(7):1345-1359.

doi: 10.1111/add.16730. Epub 2024 Dec 19.

Lisdexamfetamine in the treatment of methamphetamine dependence: A randomised, placebo-controlled trial

Nadine Ezard^{1

2

3

4}, Brendan Clifford^{1

2

3

4}, Krista J Siefried^{1

2

3

4}, Robert Ali⁵, Adrian Dunlop^{4

6

7}, Rebecca McKetin³, Raimondo Bruno^{3

8}, Andrew Carr⁹, James Ward¹⁰, Michael Farrell³, Robert Graham^{4

11}, Paul Haber^{4

12

13}, Dan Lubman^{14

15}, Mark W Donoghoe^{16

17}, Nick Olsen¹⁸, Amanda Baker^{3

6}, Michelle Hall⁴, Shalini Arunogiri^{14

15}, Nicholas Lintzeris^{4

13

19}; LiMA Investigator Group

Collaborators, Affiliations

Collaborators

LiMA Investigator Group:
Anthony Gill², Craig Rodgers², Mark Montebello^{4

13

20}, Will Liaw^{5

21}, Zhixin Liu²⁰

Affiliations

¹ National Centre for Clinical Research on Emerging Drugs, University of New South Wales, Sydney, Australia.
² Alcohol and Drug Service, St Vincent's Hospital Sydney, Sydney, Australia.
³ National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.
⁴ Drug and Alcohol Clinical Research and Improvement Network, NSW Health, Sydney, Australia.
⁵ Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.
⁶ University of Newcastle, Newcastle, Australia.
⁷ Hunter New England Local Health District, Newcastle, Australia.
⁸ School of Psychological Sciences, University of Tasmania, Hobart, Australia.
⁹ Applied Medical Research, St Vincent's Hospital, Sydney, Australia.
¹⁰ Poche Centre for Indigenous Health, University of Queensland, Queensland, Australia.
¹¹ Western Sydney Local Health District, Sydney, Australia.
¹² Sydney Local Health District, Sydney, Australia.
¹³ Discipline of Addiction Medicine, University of Sydney, Sydney, Australia.
¹⁴ Turning Point, Eastern Health, Melbourne, Australia.
¹⁵ Monash Addiction Research Centre, Eastern Health Clinical School, Monash University, Melbourne, Australia.
¹⁶ Clinical Research Unit, University of New South Wales, Sydney, Australia.
¹⁷ Kirby Institute, University of New South Wales, Sydney, Australia.
¹⁸ Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia.
¹⁹ Drug and Alcohol Services, South Eastern Sydney Local Health District, Sydney, Australia.
²⁰ Northern Sydney Local Health District, Sydney, Australia.
²¹ Drug and Alcohol Service of South Australia, Adelaide, Australia.

PMID: 39701142
PMCID: PMC12128569
DOI: 10.1111/add.16730

Randomized Controlled Trial

Lisdexamfetamine in the treatment of methamphetamine dependence: A randomised, placebo-controlled trial

Nadine Ezard et al. Addiction. 2025 Jul.

. 2025 Jul;120(7):1345-1359.

doi: 10.1111/add.16730. Epub 2024 Dec 19.

Authors

Collaborators

LiMA Investigator Group:
Anthony Gill², Craig Rodgers², Mark Montebello^{4

13

20}, Will Liaw^{5

21}, Zhixin Liu²⁰

Affiliations

¹ National Centre for Clinical Research on Emerging Drugs, University of New South Wales, Sydney, Australia.
² Alcohol and Drug Service, St Vincent's Hospital Sydney, Sydney, Australia.
³ National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.
⁴ Drug and Alcohol Clinical Research and Improvement Network, NSW Health, Sydney, Australia.
⁵ Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.
⁶ University of Newcastle, Newcastle, Australia.
⁷ Hunter New England Local Health District, Newcastle, Australia.
⁸ School of Psychological Sciences, University of Tasmania, Hobart, Australia.
⁹ Applied Medical Research, St Vincent's Hospital, Sydney, Australia.
¹⁰ Poche Centre for Indigenous Health, University of Queensland, Queensland, Australia.
¹¹ Western Sydney Local Health District, Sydney, Australia.
¹² Sydney Local Health District, Sydney, Australia.
¹³ Discipline of Addiction Medicine, University of Sydney, Sydney, Australia.
¹⁴ Turning Point, Eastern Health, Melbourne, Australia.
¹⁵ Monash Addiction Research Centre, Eastern Health Clinical School, Monash University, Melbourne, Australia.
¹⁶ Clinical Research Unit, University of New South Wales, Sydney, Australia.
¹⁷ Kirby Institute, University of New South Wales, Sydney, Australia.
¹⁸ Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia.
¹⁹ Drug and Alcohol Services, South Eastern Sydney Local Health District, Sydney, Australia.
²⁰ Northern Sydney Local Health District, Sydney, Australia.
²¹ Drug and Alcohol Service of South Australia, Adelaide, Australia.

PMID: 39701142
PMCID: PMC12128569
DOI: 10.1111/add.16730

Abstract

Aims: This study tested the efficacy and safety of a 12-week course of lisdexamfetamine in reducing methamphetamine use, an outcome which is associated with improvements in health and wellbeing, in people dependent on methamphetamine.

Design, setting and participants: This study was a randomised double-blind placebo-controlled trial conducted in six specialist outpatient clinics in Adelaide, Melbourne, Newcastle and Sydney, Australia (2018-2021). Participants were164 adults with methamphetamine dependence, reporting at least 14 use days out of the previous 28 days (62% male, 38% female, < 1% other; mean age 39 years).

Interventions: Participants were randomly allocated 1:1 to a 15-week regimen of lisdexamfetamine (1-week induction to 250 mg, 12-week maintenance regimen, 2-week reduction; n = 80) or matched placebo (n = 84), followed-up to Week 19.

Measurements: The primary efficacy measure was past 28-day methamphetamine use at Week 13. Safety was assessed by adverse event rates. Secondary measures included methamphetamine use during the 12-week treatment period and treatment satisfaction.

Findings: Nine randomized participants did not start treatment (five were allocated to lisdexamfetamine and four allocated to placebo) and were excluded from the analyses. Fifty-seven per cent of participants were retained on study medication to primary end-point. There was only weak evidence of a lisdexamfetamine benefit at 13 weeks [adjusted difference in days of methamphetamine use = 2.2, 95% confidence interval (CI) = -0.5 to 5.0; P = 0.49]. However, throughout the whole 12-week treatment maintenance phase, the lisdexamfetamine group had fewer days of methamphetamine use in total (difference = 8.8, 95% CI = 2.7-15.0; P = 0.005). The lisdexamfetamine group reported greater self-reported treatment effectiveness [odds ratio (OR) = 2.89, 95% CI = 1.67-5.02; P < 0.001] and treatment satisfaction (OR = 3.80, 95% CI = 1.93-7.47; P < 0.001). Adverse events with lisdexamfetamine included nausea. Serious adverse events occurred in four (5%) of participants who received lisdexamfetamine.

Conclusions: Lisdexamfetamine appears to reduce methamphetamine use over a 12-week treatment period, although there is only weak evidence that reduced use is maintained during the last 4 weeks.

Keywords: Clinical trial; lisdexamfetamine; methamphetamine; methamphetamine dependence; methamphetamine use disorder; non‐abstinence outcomes; randomized controlled trial; stimulants.

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Conflict of interest statement

D.L. is supported by a NHMRC Investigator Grant (1196892). M.F. has received unrestricted funding for research purposes from Indivior and Sequiiris. M.M. has been an advisory board member for AbbVie Australia and Pfizer Australia, both unrelated to this project. N.L. has received funding from NHMRC, Camurus AB and Indivior for unrelated research. R.B. was an investigator on an untied education grant from Mundipharma to conduct post‐marketing surveillance on oxycodone and an untied educational grant from Reckitt‐Benckiser to develop a scale to identify extra medical use of pharmaceutical opioids. S.A. has received speaker honoraria from Camurus, Indivior, Gilead and Janssen for work unrelated to this study. All other authors have no relevant conflicts to declare.

Figures

**FIGURE 1**
Consolidated Standards of Reporting Trials (CONSORT) diagram trial profile.

**FIGURE 3**
Primary outcome (days of methamphetamine use).

See this image and copyright information in PMC

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Lisdexamfetamine in the treatment of methamphetamine dependence: A randomised, placebo-controlled trial

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Lisdexamfetamine in the treatment of methamphetamine dependence: A randomised, placebo-controlled trial

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