Lisdexamfetamine may be helpful in treating methamphetamine dependence

By Melanie Hinze

Australian researchers have found that lisdexamfetamine appears to reduce methamphetamine use over a 12-week treatment period in people dependent on methamphetamine.

Published in Addiction, the randomised, double-blind, placebo-controlled trial included 164 adults (62% male, 38% female, <1% other; mean age 39 years) with methamphetamine dependence from six specialist outpatient clinics in Adelaide, Melbourne, Newcastle and Sydney from 2018 to 2021. Participants had reported using methamphetamine on at least 14 of the past 28 days.

The researchers randomly allocated participants 1:1 to a 15-week regimen of lisdexamfetamine (n=80) or a matched placebo (n=84). The lisdexamfetamine regimen consisted of a one-week induction to 250 mg/day, a 12-week maintenance regimen, and then a two-week reduction. Follow up continued to week 19.

The primary efficacy measure was past 28-day methamphetamine use at week 13, and secondary measures included methamphetamine use during the 12-week treatment period and treatment satisfaction.

Nine participants (five in the treatment group; four in the placebo group) did not start treatment and were therefore excluded from the analyses, and 57% stayed on medication through to the endpoint.

The researchers found that although there was only weak evidence of a lisdexamfetamine benefit at 13 weeks, the lisdexamfetamine group had fewer days of methamphetamine use in total throughout the 12-week maintenance phase compared with the placebo group (average 8.8 fewer days’ use). This group also had greater self-reported treatment effectiveness (2.9 times higher) and treatment satisfaction (3.8 times higher) than the placebo group.

Adverse events with lisdexamfetamine included nausea and severe adverse events occurred in four (5%) participants in the medication group.

A limitation of the study that impacted the statistical strength of the findings was that only 57% of the treatment group remained on the study medication, the researchers said; however, they noted this retention level was consistent with other outpatient studies for methamphetamine-use disorder.

Lead author Professor Nadine Ezard, Clinical Director of the Alcohol and Drug service at St Vincent’s Hospital in Sydney and Conjoint Professor with the National Drug and Alcohol Research Centre, UNSW Sydney, said the findings were in line with new guidance from the American Society of Addiction Medicine, which recommended these kinds of off-label prescriptions by specialists.

‘For GPs, it is important to be aware that there are these emergent treatment options for people with really severe methamphetamine-use disorder,’ said Professor Ezard.

‘The other thing I think is probably important to highlight is that reduction in use is considered a treatment goal by many people, so we don’t need to be so focused just on people stopping completely,’ she added.

Addiction 2024; 1-15; doi: 10.1111/add.16730.