A retrospective analysis of two randomized trials of bupropion for methamphetamine dependence: Suggested guidelines for treatment discontinuation/augmentation

Abstract

Background Two clinical trials have shown efficacy for bupropion in treating methamphetamine (MA) dependence among those with moderate baseline MA use. However, treatment response is highly variable and it is unclear what duration of treatment is necessary to determine if maintaining the treatment course is indicated or if discontinuation or augmentation is appropriate. The present study assessed the relationship among early bupropion treatment response for moderate MA users and end-of-treatment (EOT) abstinence. These data provide estimates of the duration of treatment and the degree of responsiveness required to persist in bupropion treatment. Methods Participants with moderate baseline MA use in the bupropion condition of two randomized double-blind placebo controlled trials were included. The relationship between early treatment response and EOT outcomes was assessed with Receiver Operating Characteristic (ROC) curves. Results With thrice weekly urine drug testing, excellent predictive power was established in the first two weeks of treatment. The inability to achieve at least three MA negative samples in the first two weeks is associated with greater than 90% likelihood of treatment failure. More closely approximating clinical settings, once-weekly testing featured reliable predictive power within three weeks, suggesting that the failure to produce at least two clean samples in the first three weekly visits confers high risk of treatment failure. Discussion The findings provide preliminary evidence to guide clinical decisions for moderate MA users receiving bupropion. The results are consistent with data from the smoking cessation literature and may highlight the importance of early response in addiction treatment.

Placebo-group responders in methamphetamine pharmacotherapy trials: The role of immediate establishment of abstinence.

“…We recently examined moderate users of methamphetamine from two clinical trials of bupropion – a subgroup in which the medication has demonstrated preliminary efficacy. Results were consistent with the findings reported here suggesting the possibility that immediate responsiveness may be critically important for a range of addiction treatments (Brensilver, Heinzerling, Swanson, & Shoptaw, 2012). …”

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

“…However, the present study included MA users seeking to stop or reduce MA use and a larger sample size, and participants were monitored for MA use as opposed to psychological measures of reinforcement. Furthermore, our data appear to support the conclusions of Brensilver et al (2012), whose retrospective analyses of other bupropion research (Elkashef et al, 2008 and Shoptaw et al, 2008) suggest that treatment response can be predicted after two to three weeks (Figure 2); responders and non-responders in this study appeared to diverge in terms of MA-negative UDS by week 3.…”

Psychostimulants

“…A retrospective analysis of these two studies suggested that bupropion may be effective in patients with only moderate baseline methamphetamine use. Thereby, the failure to provide at least two negative urine samples in the first three weekly tests would confer an enhanced risk of treatment failure (Brensilver, Heinzerling, Swanson, & Shoptaw, 2012). However, abstinence was significantly higher in those individuals with high medication adherence compared to those with low adherence in a patient population with low methamphetamine abuse (Heinzerling et al, 2014).…”