Lisdexamfetamine in the treatment of methamphetamine dependence, a randomised controlled trial
Background: Methamphetamine dependence is a growing global health concern. Lisdexamfetamine is a potential agonist therapy and has not been well studied. We aimed to determine the safety and efficacy of 12-weeks of 250mg lisdexamfetamine daily.
Methods: We conducted a randomised double-blind placebo-controlled trial of adults with methamphetamine dependence reporting at least 14 days use out of the previous 28 in six Australian specialist outpatient clinics (ACTRN12617000657325). We randomised consenting participants 1:1 to the intervention (one week induction, 12 weeks 250mg daily, 2 weeks reducing dose) or identical matched placebo control condition, alongside the offer of up to four sessions of cognitive behavioural therapy. The primary efficacy measure was change from baseline in days of methamphetamine use over the past 28 days, and secondary measures were treatment satisfaction, general health, and quality of life. We conducted an intention-to-treat analysis using a likelihood-based mixed effects regression model.
Results: 155 participants (75 lisdexamfetamine, 80 placebo) were included in the analysis. There was a non-significant between-group difference in the odds ratio of past 28-day methamphetamine use at the end of 12 weeks treatment (OR 0.62, 95% CI 0.36 to 1.08; P=0.09), the primary endpoint. Participants in the lisdexamfetamine group had an average 9.5 fewer days use over the 12-week treatment period (95% CI 3.2 to 15.8; P=0.003), and greater treatment satisfaction (OR 3.6, 95% CI 1.9 to 6.9; p<0.001) and self-reported overall health (OR 3.1, 95% CI 1.1 – 8.8; P=0.03). There were no important safety concerns.
Conclusion: Lisdexamfetamine resulted in reduction of use over the 12-week treatment period but not the last four weeks of treatment, accompanied by positive changes in self-reported well-being measures, warranting further exploration of lisdexamfetamine in treatment of methamphetamine dependence.
