A protocol for high-dose lisdexamfetamine and contingency management, alone or in combination, for the treatment of methamphetamine use disorder: The ASCME study.

Background: The prevalence of methamphetamine use disorder is increasing in North America. Well-evidenced treatment options are currently limited to behavioural interventions, with contingency management (CM) regarded as the most effective approach. Psychostimulants have been identified as a potentially promising treatment for methamphetamine use disorder, particularly at higher doses. This study was designed to examine the effectiveness of a high-dose daily psychostimulant (lisdexamfetamine; LDX) and CM, both alone and in combination, in addition to treatment-as-usual (TAU) for the treatment of moderate-to-severe methamphetamine use disorder.

Methods: The ASCME study is a multicentre, four-arm, blinded, randomized, placebo-controlled clinical trial examining the effectiveness of adding LDX (250 mg) and CM, alone or in combination, to TAU in reducing days of methamphetamine use among adults with moderate-to-severe methamphetamine use disorder. A total of 440 participants will be randomized across 5 sites to 12 weeks of 1) LDX + TAU + CM; 2) LDX + TAU; 3) placebo + CM + TAU; and 4) placebo + TAU. The primary outcome is reduction in days of self-reported methamphetamine use, with secondary outcomes including treatment retention, sustained abstinence, safety, medication adherence, satisfaction, and quality of life.

Conclusion: This study will be the largest study to date examining the effectiveness of a prescribed psychostimulant in the treatment of methamphetamine use disorder, and the first of its kind to employ a four-arm approach to evaluate the added benefit of its combination with CM on psychostimulant treatment. The development of pharmacologic treatments for methamphetamine use disorder remains an urgent research goal.