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

This randomized, double-blind, placebo-controlled trial, known as the LiMA study, investigated the efficacy and safety of a 12-week regimen of lisdexamfetamine (up to 250 mg daily) for treating adults with methamphetamine dependence. Researchers sought to determine if this agonist-like pharmacotherapy could reduce methamphetamine use in an outpatient population recruited across six Australian clinics between 2018 and 2021.

164 participants were randomized 1:1 to receive either lisdexamfetamine or a matched placebo. The intervention included a one-week induction phase, a 12-week maintenance phase at 250 mg, and a two-week reduction taper. All participants were also offered manual-guided cognitive behavioral therapy (CBT). The primary outcome measure was the number of days of self-reported methamphetamine use during the 28-day period leading up to the Week 13 primary end-point. The study design was adapted mid-trial to accommodate COVID-19 public health restrictions.

Statistical analysis showed a significant reduction in the total number of days of methamphetamine use across the entire 12-week maintenance phase for the lisdexamfetamine group. However, when examining the specific primary end-point at Week 13, the evidence for a sustained benefit was weak, failing to reach statistical significance. Notably, participants in the lisdexamfetamine group reported significantly higher levels of treatment satisfaction and perceived effectiveness compared to the placebo group. Safety monitoring indicated that while serious adverse events occurred in 5% of the medication group, the treatment was generally tolerable, with nausea being the most frequently reported side effect.

Currently, there are no approved pharmacotherapies specifically indicated for methamphetamine dependence. While this study suggests that high-dose lisdexamfetamine may help reduce the frequency of use, the lack of a sustained effect at the 13-week mark leaves the clinical utility of this approach somewhat uncertain. The positive patient-reported outcomes, however, underscore a potential demand for such treatments and highlight the need for further research, perhaps with larger samples or different dosing strategies, to determine if these medications can provide consistent, long-term benefits.