Lisdexamfetamine for methamphetamine withdrawal: clinical trial

What does participation involve?

This trial is a multi-site, two arm, placebo-controlled randomised controlled trial. Participants will be admitted to a hospital withdrawal management unit for 7 nights (8 days), and receive either a tapering dose of lisdexamphetamine, or matched placebo. 

Lisdexamfetamine doses will start at 250mg once daily, reducing through the admission. We will them follow up with participants via telephone for 3 months after they leave hospital. While in hospital, participants can also receive standard of care withdrawal management (e.g. psychosocial support) to help manage symptoms if needed.

After the 7 nights there is no more trial medication, however standard care ongoing treatment individualised to the participant, including but not limited to ongoing counselling or referral to residential rehabilitation services, will be provided. 

The primary outcome of this study is effectiveness, defined by a reduction in MA withdrawal symptoms. 

Secondary outcomes include safety, retention in treatment, treatment satisfaction, sleep, other medication use, long term withdrawal symptoms, cost effectiveness, post-discharge substance use and service utilisation. We are also conducting a qualitative sub-study investigating the experiences of Aboriginal and Torres Strait Islander participants in this study.

Study locations and Contact Details

This study will be conducted at five sites around Australia:

• St Vincent’s Hospital Sydney 
  svhs.adresearch@svha.org.au or 0411 712 276
   
• Concord Repatriation General Hospital, Sydney
  SLHD-OLAMStudy@health.nsw.gov.au or 0436 801 914
   
• Belmont Hospital, Newcastle 
  HNELHD-DACSResearch@health.nsw.gov.au or 0455 051 469 or 0417 656 352
   
• Box Hill Hospital, Melbourne 
  trialstp@easternhealth.org.au or 0479 146 374
   
• Next Step Drug and Alcohol Services, Perth (contact details to be provided closer to recruitment opening)

If you don’t hear from us after completing the expression of interest form and are still interested, please contact the study coordinators at your preferred site using the details above.

Why we're doing this research

Methamphetamine withdrawal

Methamphetamine (MA) is now the most common illicit drug for which treatment is sought in Australia, and First Nations people are eight times more likely to require treatment for MA use disorder than other Australians. 

Poorly managed MA withdrawal is a major obstacle to achieving their treatment goals, and 88-97% of people who regularly use MA experience withdrawal. MA withdrawal is often the first step in the treatment journey, yet retention in withdrawal treatment is shorter than for other drug classes.

Untreated withdrawal limits capacity to achieve abstinence and sustains the cycle of dependence. Withdrawal treatment for substance use disorder of any drug class (e.g. nicotine, opioids, cannabis) aims to reduce severity of symptoms, driving retention and post-withdrawal treatment engagement. 

There is no effective treatment for MA withdrawal. Current clinical practice is marked by poor outcomes, inconsistent approaches, and a limited evidence-base. Approaches where medications with similar modes of action are used to reduce withdrawal severity have shown promise, and are effective for other withdrawal syndromes. 

Lisdexamfetamine 

Lisdexamfetamine (LDX) is a potential medication to help manage MA withdrawal. It is a pharmacologically inactive prodrug of dexamphetamine that may help reduce the severity of withdrawal symptoms.

Our group recently completed an open-label, single-arm pilot study examined a 5-day tapering regimen of LDX starting at 250mg and decreasing by 50mg a day among adults in acute MA withdrawal over a 7-day inpatient period (n=10) demonstrating safety and feasibility of the treatment. In qualitative interviews, participants of the pilot trial reported that the intervention was highly acceptable, and thought that LDX helped create an easier withdrawal experience. 

Our aims therefore are to determine the effectiveness of lisdexamfetamine as a treatment for acute MA withdrawal in an inpatient setting. 

Watch our video abstract summarising the pilot study: 

Advisory Groups

The OLAM trial is governed by two advisory groups that ensure that the expertise of consumers, peers and community are integrated in the trial across all stages of research.

The OLAM RCT Consumer Advisory Group plays a vital role in ensuring that the lived-living experiences of people who use methamphetamine are embedded throughout the trial. The group provides critical input into the design, implementation and delivery of results with participant needs, preferences and safety in mind. The group is chaired by OLAM’s Consumer Investigator Jack Nagle (Real Drug Talk), and members are located across New South Wales, Victoria and Western Australia to cover representation of local demographics at each study site. 

The Edith Collins Aboriginal Reference Group governs research undertaken by the Edith Collins Centre First Nation’s research program, led by co-investigator of the OLAM trial, Associate Professor Michael Doyle. The group provides cultural governance and oversight, ensuring that the study prioritises cultural safety, respect, and is responsive to the needs of Aboriginal and Torres Strait Islander peoples. The group advises on all aspects of the study, including the embedded qualitative study exploring First Nations participants’ experiences of the intervention. Their leadership supports ethical engagement, promotes Indigenous data sovereignty, and strengthens the relevance of the trial for Aboriginal communities across Australia.

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