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

AIMS

This study tested the efficacy and safety of a 12-week course of lisdexamfetamine in reducing methamphetamine use, an outcome which is associated with improvements in health and wellbeing, in people dependent on methamphetamine.

DESIGN, SETTING AND PARTICIPANTS: This study was a randomised double-blind placebo-controlled trial conducted in six specialist outpatient clinics in Adelaide, Melbourne, Newcastle and Sydney, Australia (2018-2021). Participants were164 adults with methamphetamine dependence, reporting at least 14 use days out of the previous 28 days (62% male, 38% female, < 1% other; mean age 39 years).

INTERVENTIONS

Participants were randomly allocated 1:1 to a 15-week regimen of lisdexamfetamine (1-week induction to 250 mg, 12-week maintenance regimen, 2-week reduction; n = 80) or matched placebo (n = 84), followed-up to Week 19.

MEASUREMENTS

The primary efficacy measure was past 28-day methamphetamine use at Week 13. Safety was assessed by adverse event rates. Secondary measures included methamphetamine use during the 12-week treatment period and treatment satisfaction.

FINDINGS

Nine randomized participants did not start treatment (five were allocated to lisdexamfetamine and four allocated to placebo) and were excluded from the analyses. Fifty-seven per cent of participants were retained on study medication to primary end-point. There was only weak evidence of a lisdexamfetamine benefit at 13 weeks [adjusted difference in days of methamphetamine use = 2.2, 95% confidence interval (CI) = -0.5 to 5.0; P = 0.49]. However, throughout the whole 12-week treatment maintenance phase, the lisdexamfetamine group had fewer days of methamphetamine use in total (difference = 8.8, 95% CI = 2.7-15.0; P = 0.005). The lisdexamfetamine group reported greater self-reported treatment effectiveness [odds ratio (OR) = 2.89, 95% CI = 1.67-5.02; P < 0.001] and treatment satisfaction (OR = 3.80, 95% CI = 1.93-7.47; P < 0.001). Adverse events with lisdexamfetamine included nausea. Serious adverse events occurred in four (5%) of participants who received lisdexamfetamine.

CONCLUSIONS

Lisdexamfetamine appears to reduce methamphetamine use over a 12-week treatment period, although there is only weak evidence that reduced use is maintained during the last 4 weeks.