Safety and tolerability of oral lisdexamfetamine in adults with methamphetamine dependence: a phase-2 dose-escalation study

Abstract

ObjectivesTo examine the safety of an agonist-type treatment, lisdexamfetamine (LDX), at 250 mg/day among adults with methamphetamine (MA) dependence.DesignA dose-escalating, phase-2, open-label, single-group study of oral LDX at two Australian drug treatment services.SettingThe study was conducted at two Australian stimulant use disorder treatment clinics.ParticipantsThere were 16 participants: at least 18 years old, MA dependent for at least the preceding 2 years using ICD-10 criteria, reporting use of MA on at least 14 of the preceding 28 days.InterventionsDaily, supervised LDX of 100–250 mg, single-blinded to dose, ascending-descending regimen over 8 weeks (100–250 mg over 4 weeks; followed by 4-week dose reduction regimen, 250–100 mg). Participants were followed through to week 12.OutcomesPrimary outcomes were safety, drug tolerability and regimen completion at the end of week 4. Participants were followed to week 12. Secondary outcomes included: change in MA use; craving; withdrawal; severity of dependence; risk behaviour; change in other substance use; medication acceptability; potential for non-prescription use; adherence and neurocognitive functioning.ResultsFourteen of 16 participants (87.5%) completed escalation to 250 mg/day. Two participants withdrew from the trial in the first week: one relocated away from the study site, the other self-withdrew due to a possible, known side effect of LDX (agitation). There was one serious adverse event of suicidal ideation which resolved. All other adverse events were mild or moderate in severity and known side effects of LDX. No participant was withdrawn due to adverse events. MA use decreased from a median of 21 days (IQR: 16–23) to 13 days (IQR: 11–17) over the 4-week escalation period (p=0.013).ConclusionsLDX at a dose of up to 250 mg/day was safe and well tolerated by study participants, warranting larger trials as a pharmacotherapy for MA dependence.Trial registration numberACTRN12615000391572.

Association of Pharmacological Treatments and Hospitalization and Death in Individuals With Amphetamine Use Disorders in a Swedish Nationwide Cohort of 13 965 Patients

“…Lisdexamphetamine is licensed for doses ranging from 30 to 70 mg/d in the treatment of ADHD and binge eating disorder in non–stimulant-dependent populations, although there is available safety data from the use of lisdexamphetamine up to 250 mg/d. In this study, 1511 persons (10.8%) were taking lisdexamphetamine. The most beneficial outcome was observed with doses from 45 to 85 mg/d.…”

Continuing Increase in Stimulant Dependence – Time to Implement Medical Treatment

“…Finally, it is possible that local regulatory agencies may have objections to treatment with high doses, as suggested here. To address that, safety studies have been conducted with lisdexamphetamine for AUD 29 and CUD 30 using up to 250mg/day, and that dose was safe and well-tolerated in both trials. As evidence of the safety of higher-dose prescription psychostimulants builds up, regulatory bodies around the world could be more prone to adopting them.…”

Clinical management of psychostimulant withdrawal: review of the evidence

“…Two early pilots of mirtazapine for MA withdrawal showed some signal, although at doses that are twice that found efficacious to reduce MA use in treatment trials (30 mg/day [94,95] A key trial evaluating the value of using a psychostimulant in initial abstinence to treat acute-phase withdrawal symptoms is in the field in Australia at this time [96].…”