Randomised double blind placebo controlled trial of oral lisdexamfetamine for methamphetamine withdrawal

Investigators: Prof Nadine Ezard,  Dr Krista Siefried, Prof Adrian Dunlop, Prof Nicholas Lintzeris, Prof Steven Shoptaw, Prof Paul Haber, Prof Andrew Carr, Assoc Prof Michael Doyle, Dr Shalini Arunogiri, Michael Clifford, Dr Frances Levin, A/Prof Yvonne Bonomo, Prof Daniel Lubman, Jack Nagle, Duran Cox, Mr Carl Moller, Dr Michael Christmass, Mr Liam Acheson, Assoc Prof Rebecca McKetin, Dr Mark Donoghoe

Funder: NHMRC,  Clinical Trials and Cohort Studies

Australia has the highest prevalence of methamphetamine (MA) dependence globally. Rates of frequent MA use have almost doubled over the past decade, overdose deaths have quadrupled, and treatment demand has increased 5-fold, costing Australia an estimated $5 billion a year. Acute MA withdrawal is experienced by 88-97% of people who use MA regularly, and is of such severity that it perpetuates drug-use and precludes engagement in treatment for MA use disorder. Poorly managed MA withdrawal is a major obstacle to achieving abstinence from MA, yet there is no effective treatment. Agonist medications are used to effectively treat other withdrawal syndromes such as nicotine for nicotine withdrawal; lisdexamfetamine (LDX) is a promising agonist candidate for the treatment of MA withdrawal. Our world-class team of researchers, treatment providers and people with lived experience conducted a single-arm feasibility study of LDX for acute MA withdrawal and demonstrated that a tapering LDX dose regimen was safe, feasible, and reduced severity of withdrawal symptoms. This randomised controlled trial will test whether LDX will safely reduce withdrawal symptoms. The study will enrol 184 methamphetamine dependent adults across 6 Australian sites. They will be randomised to receive a tapering dose regimen of oral LDX or identical placebo for 7 days, and followed up in the community to Day 28. The primary outcome is differences in mean withdrawal severity over 7 days. Secondary outcomes include safety, retention in treatment, treatment satisfaction, MA abstinence, engagement in post-withdrawal treatment and well-being. A health economic analysis and First Nations qualitative experience sub-study will be conducted. As early abstinence is a powerful predictor of longer-term abstinence and early treatment engagement is associated with better substance use outcomes, LDX may become the first treatment for MA withdrawal and has the potential to change the treatment landscape.

This project is a collaboration between Monash University, University of New South Wales (UNSW), Hunter New England Local Health District, University of California Los Angeles, Royal Prince Alfred Hospital, St Vincent's Centre for Applied Medical Research, University of Sydney, Columbia University, St Vincent's Hospital Melbourne, Real Drug Talk (Aus) Pty Ltd (trading as Connections Based Living), St Vincent's Hospital Sydney, & Government of Western Australia Mental Health Commission.