Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence

Ezard, Nadine; Dunlop, Adrian; Clifford, Brendan; Bruno, Raimondo; Carr, Andrew; Bissaker, Alexandra; Lintzeris, Nicholas

doi:10.1186/s12888-016-1141-x

Cited by 11 publications

(6 citation statements)

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“…Commonly used psychosocial treatments include cognitive behavioral therapy ( 14 ), contingency management ( 15 , 16 ), motivational interviewing ( 17 ), and so on. Meanwhile, researchers explored many medications of MA treatment that frequently target dopaminergic, serotonergic, GABAergic, and/or glutamatergic brain pathways such as dexamphetamine ( 18 , 19 ), methylphenidate ( 20 , 21 ), naltrexone ( 22 , 23 ), topiramate ( 24 , 25 ), and so on. Therefore, it makes sense to predict the therapeutic effect before treatment, in order to allow doctors to identify the optimal treatment plan at the individual level.…”

Section: Introductionmentioning

confidence: 99%

Treatment Response Prediction and Individualized Identification of Short-Term Abstinence Methamphetamine Dependence Using Brain Graph Metrics

Cui

Yang

et al. 2021

Front. Psychiatry

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Background: The abuse of methamphetamine (MA) worldwide has gained international attention as the most rapidly growing illicit drug problem. The classification and treatment response prediction of MA addicts are thereby paramount, in order for effective treatments to be more targeted to individuals. However, there has been limited progress.Methods: In the present study, 43 MA-dependent participants and 38 age- and gender-matched healthy controls were enrolled, and their resting-state functional magnetic resonance imaging data were collected. MA-dependent participants who showed 50% reduction in craving were defined as responders to treatment. The present study used the machine learning method, which is a support vector machine (SVM), to detect the most relevant features for discriminating and predicting the treatment response for MA-dependent participants based on the features extracted from the functional graph metrics.Results: A classifier was able to differentiate MA-dependent subjects from normal controls, with a cross-validated prediction accuracy, sensitivity, and specificity of 73.2% [95% confidence interval (CI) = 71.23–74.17%), 66.05% (95% CI = 63.06–69.04%), and 80.35% (95% CI = 77.77–82.93%), respectively, at the individual level. The most accurate combination of classifier features included the nodal efficiency in the right middle temporal gyrus and the community index in the left precentral gyrus and cuneus. Between these two, the community index in the left precentral gyrus had the highest importance. In addition, the classification performance of the other classifier used to predict the treatment response of MA-dependent subjects had an accuracy, sensitivity, and specificity of 71.2% (95% CI = 69.28–73.12%), 86.75% (95% CI = 84.48–88.92%), and 55.65% (95% CI = 52.61–58.79%), respectively, at the individual level. Furthermore, the most accurate combination of classifier features included the nodal clustering coefficient in the right orbital part of the superior frontal gyrus, the nodal local efficiency in the right orbital part of the superior frontal gyrus, and the right triangular part of the inferior frontal gyrus and right temporal pole of middle temporal gyrus. Among these, the nodal local efficiency in the right temporal pole of the middle temporal gyrus had the highest feature importance.Conclusion: The present study identified the most relevant features of MA addiction and treatment based on SVMs and the features extracted from the graph metrics and provided possible biomarkers to differentiate and predict the treatment response for MA-dependent patients. The brain regions involved in the best combinations should be given close attention during the treatment of MA.

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Section: Introductionmentioning

confidence: 99%

Treatment Response Prediction and Individualized Identification of Short-Term Abstinence Methamphetamine Dependence Using Brain Graph Metrics

Cui

Yang

et al. 2021

Front. Psychiatry

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“…A phase-2, open-label, single-group trial was undertaken at two stimulant use disorder treatment outpatient clinics in New South Wales, Australia. 20 All participants provided written, informed consent prior to undergoing study assessments. An independent data safety and monitoring board reviewed safety data during and at completion of the study.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2021

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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.

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“…Eligible participants enrolled in the study will commence with 7 days of 150 mg lisdexamfetamine or placebo daily (the induction phase). 33 34 They will attend the clinic for the first 5 days for supervised administration of the study medication, recording of blood pressure, pulse and temperature, monitoring of adverse events and medication adherence counselling. On the fifth day, the participant will be provided with two additional doses self-administer orally once a day.…”

Section: Methodsmentioning

confidence: 99%

“…30 This dose has also been tolerated by non-methamphetamine dependent volunteers in a pharmacokinetic study, 31 as well as in a study in participants with schizophrenia receiving antipsychotic pharmacotherapy. 32 A recent safety dose-escalating trial of methamphetamine dependent participants with high frequency of use 33 successfully escalated 14 out of 16 participants to 250 mg lisdexamfetamine 34 ).…”

Section: Introductionmentioning

confidence: 99%

LiMA: a study protocol for a randomised, double-blind, placebo controlled trial of lisdexamfetamine for the treatment of methamphetamine dependence

et al. 2018

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IntroductionMethamphetamine dependence is a growing public health concern. There is currently no pharmacotherapy approved for methamphetamine dependence. Lisdexamfetamine (LDX) dimesylate, used in the treatment of attention-deficit hyperactivity disorder and binge eating disorder, has potential as an agonist therapy for methamphetamine dependence, and possible benefits of reduced risk of aberrant use due to its novel formulation.Methods and analysisA double-blind randomised controlled trial will be used to evaluate the efficacy of LDX in reducing methamphetamine use. The target sample is 180 participants with methamphetamine dependence of ≥2 years, using ≥14 days out of the previous 28, who have previously attempted but not responded to treatment for methamphetamine use. Participants will be randomly assigned to receive either a 15-week intervention consisting of induction (1 week of 150 mg LDX or placebo), maintenance (12 weeks of 250 mg LDX or placebo) and reduction (1 week of 150 mg LDX or placebo and 1 week of 50 mg LDX or placebo). All participants will be given access to four sessions of cognitive–behavioural therapy as treatment as usual and receive a 4-week follow-up appointment. The primary outcomes are efficacy (change from baseline in days of methamphetamine use by self-report for the last 28 days at week 13 and urinalyses confirmation of methamphetamine use) and safety (treatment-related adverse events). Secondary outcomes are total number of days of self-report methamphetamine use over the 12-week active treatment, longest period of abstinence during treatment period, percentage of achieving ≥21 days abstinence, craving, withdrawal, dependence, retention, bloodborne virus transmission risk behaviour, criminal behaviour, as well measures of abuse liability, physical and mental health, other substance use, cognitive performance, psychosocial functioning, treatment retention and satisfaction. Additionally, the study will assess the cost-effectiveness of LDX relative to the placebo control.Ethics and disseminationThe study has been approved by the Human Research Ethics Committee of St. Vincent’s Hospital, Sydney, Australia (HREC/16/SVH/222). Contact the corresponding author for the full trial protocol.Trial registration numberACTRN12617000657325; Pre-results.

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Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence

Cited by 11 publications

References 50 publications

Treatment Response Prediction and Individualized Identification of Short-Term Abstinence Methamphetamine Dependence Using Brain Graph Metrics

Treatment Response Prediction and Individualized Identification of Short-Term Abstinence Methamphetamine Dependence Using Brain Graph Metrics

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

LiMA: a study protocol for a randomised, double-blind, placebo controlled trial of lisdexamfetamine for the treatment of methamphetamine dependence

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