Utilizing a Two-stage Design to Investigate the Safety and Potential Efficacy of Monthly Naltrexone Plus Once-daily Bupropion as a Treatment for Methamphetamine Use Disorder

Abstract

Objectives This two-stage open-label pilot study evaluated the safety and potential efficacy of naltrexone plus bupropion as a pharmacotherapy for methamphetamine (MA) use disorder. Methods The study was conducted in two stages of recruitment across 3 sites; 20 participants were enrolled in Stage 1, and 29 participants were enrolled in Stage 2. Eight weeks of open-label pharmacotherapy with a combination of extended-release injectable naltrexone (XR-NTX; Vivitrol®) plus extended-release oral bupropion (BRP; Wellbutrin® XL) were provided with a smartphone-assisted medication adherence platform. Participants met DSM-5 criteria for severe MA use disorder, self-reported ≥20 days of MA use in the 30 days prior to consent, and submitted 3 MA-positive urine drug screens (UDS) out of 4 collected during screening. Participants attended clinic twice weekly for observed BRP dosing, UDS testing, assessments, and medical management; XR-NTX was administered at weeks 1 and 5. A BRP taper and follow-up visit occurred in Week 9. Results Analyses evaluated effects of XR-NTX+BRP to determine the number of “responders” according to a statistically pre-defined response criterion (6 of 8 MA-negative UDS during the last four weeks of medication). The two-stage design required that Stage 1 yield ≥3 responders to continue to Stage 2; 11 of the 49 participants met responder criteria across both stages (5 in Stage 1, 6 in Stage 2). Conclusions Under the statistical analysis plan, study “success” required ≥9 responders. With 11 responders, the study demonstrated sufficient potential of naltrexone plus bupropion as a combination pharmacotherapy for MA use disorder to warrant further study.

Extended‐release naltrexone for methamphetamine dependence among men who have sex with men: a randomized placebo‐controlled trial

“…Furthermore, our participants were actively using methamphetamine, in contrast to an earlier trial of relapse prevention among amphetamine‐dependent people . Secondly, we studied XRNTX in isolation, whereas there may be benefit when the medication is combined with other agents .…”

Medication Adherence Monitoring Using Smartphone Video Dosing in an Open-label Pilot Study of Monthly Naltrexone Plus Once-daily Bupropion for Methamphetamine Use Disorder: Feasibility and Acceptability

“…These results are better understood when examined in conjunction with the data presented in the primary outcome manuscript. Mooney et al (2016) showed that participants who responded to the medication (n ¼ 11) had high adherence rates and the selfreported (97.6%) and video-confirmed (95.2%) dosing adherence rates were very similar. In contrast, although participants who were medication nonresponders (n ¼ 38, including early withdrawals) also had high self-reported rates of adherence (92.1%), fewer doses were corroborated by video confirmation (83.4%).…”

“…Recognizing medication nonadherence as a source of serious confound and seeking to optimize oral medication adherence for a trial evaluating a promising combination pharmacotherapy for methamphetamine use disorder, we implemented a technology-assisted medication adherence component. To our knowledge, the ADAPT pilot study (Mooney et al, 2016) was the first trial that utilized a smartphone-enabled, video-confirmation strategy to remotely monitor and encourage oral medication adherence among people who use methamphetamine. The smartphone video dosing procedure was reported as feasible and well accepted by participants and staff.…”

“…Use of mobile technology was a key component of the multi-site Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT) for Methamphetamine Use Disorder trial, sponsored by the National Drug Abuse Treatment Clinical Trials Network (Mooney et al, 2016). The aim of ADAPT was to evaluate the safety and potential efficacy of a new pharmacotherapy in a brief period with few participants.…”

Gaps in the ice: Methamphetamine in Australia; its history, treatment, and ramifications for users and their families

“…) or combination slow release naltrexone plus bupropion (Mooney et al . ). In general, all effects were either small to moderate or not replicated in more recent larger randomized control studies.…”