Lisdexamfetamine reduced reported methamphetamine-use days across a 12-week treatment period, but the trial’s primary endpoint at week 13 was not statistically significant. The study provides a treatment signal with important qualifications, rather than an unqualified positive result.
Ezard and colleagues randomized 164 adults with methamphetamine dependence at six Australian clinics to lisdexamfetamine or placebo. The regimen included induction to 250 mg, 12 weeks of maintenance and a taper. Nine randomized participants never started treatment and were excluded from analysis. This was a supervised clinical research regimen, not a dosing recommendation. Lisdexamfetamine is a prodrug of dexamphetamine, not methamphetamine.
The primary outcome was self-reported methamphetamine-use days during the previous 28 days at week 13. The estimated benefit was 2.2 fewer days, with a confidence interval spanning no difference and p = 0.49. That comparison did not establish a statistically significant benefit at the primary endpoint.
Across the full 12-week maintenance phase, the active-treatment group reported 8.8 fewer use days (95% confidence interval 2.7 to 15.0 fewer; p = 0.005). Treatment satisfaction was also higher. However, the proportion of methamphetamine-negative urines did not significantly differ between groups. A favorable secondary self-report outcome should not be converted into a claim of biologically confirmed abstinence.
Urine samples were screened for amphetamine-type substances and drug type was confirmed by gas chromatography–mass spectrometry. Distinguishing methamphetamine from amphetamine matters when the assigned medication produces dexamphetamine. Missing urine tests were counted positive in the specified urine outcomes. Only 57% remained on study medication to the primary endpoint, and four participants receiving lisdexamfetamine experienced serious adverse events. Attrition, outcome definitions and safety findings belong in the interpretation alongside the favorable secondary result. None of these treatment outcomes establishes individual impairment from a positive drug test.
See also why self-report and urine outcomes can disagree.