Bupropion for the Treatment of Methamphetamine Dependence

Abstract

Bupropion was tested for efficacy in increasing weeks of abstinence in methamphetamine-dependent patients, compared to placebo. This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 30-day follow-up. Five outpatient substance abuse treatment clinics located west of the Mississippi participated in the study. One hundred and fifty-one treatment-seekers with DSM-IV diagnosis of methamphetamine dependence were consented and enrolled. Seventy-two participants were randomized to placebo and 79 to sustained-release bupropion 150 mg twice daily. Patients were asked to come to the clinic three times per week for assessments, urine drug screens, and 90-min group psychotherapy. The primary outcome was the change in proportion of participants having a methamphetamine-free week. Secondary outcomes included: urine for quantitative methamphetamine, self-report of methamphetamine use, subgroup analyses of balancing factors and comorbid conditions, addiction severity, craving, risk behaviors for HIV, and use of other substances. The generalized estimating equation regression analysis showed that, overall, the difference between bupropion and placebo groups in the probability of a non-use week over the 12-week treatment period was not statistically significant (p ¼ 0.09). Mixed model regression was used to allow adjustment for baseline factors in addition to those measured (site, gender, level of baseline use, and level of symptoms of depression). This subgroup analysis showed that bupropion had a significant effect compared to placebo, among male patients who had a lower level of methamphetamine use at baseline (po0.0001). Comorbid depression and attention-deficit/ hyperactivity disorder did not change the outcome. These data suggest that bupropion, in combination with behavioral group therapy, was effective for increasing the number of weeks of abstinence in participants with low-to-moderate methamphetamine dependence, mainly male patients, regardless of their comorbid condition.

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

“…In a post hoc analysis, bupropion reduced MA use significantly more than placebo among participants with light-but not heavy-MA use as defined by the frequency of MA positive urine drug screens during the baseline period. These findings are consistent with those of a previous trial that found bupropion to be more effective in reducing MA use among male participants with low-to-moderate self-reported MA use at baseline (Elkashef et al, 2007), although we were unable to directly replicate the previous study's findings due to the small sample size in our study. Bupropion also significantly reduced ad libitum cigarette smoking relative to placebo despite the lack of any psychosocial/behavioral treatment targeting cigarette smoking cessation, which is consistent with bupropion's efficacy for smoking cessation (Hughes et al, 2007) and suggests that the failure to detect a main effect for bupropion on MA use was not due to problems with internal validity.…”

“…Interestingly, the previous study of bupropion for MA dependence failed to find an effect for bupropion on cigarette smoking relative to placebo (Elkashef et al, 2007), and the reason for this discrepancy between the two studies is not clear. Considering that the prevalence of cigarette smoking among illicit drug users, including MA users, is as high as 70%-90% (Budney et al, 1993;Grant et al, 2004;Kalman et al, 2005;Richter et al, 2002) and that cigarette smoking is associated with poor health outcomes among illicit drug users, above and beyond those found in nonsmoking drug users (Hser et al, 1994;Hurt et al, 1996), the identification of smoking cessation treatments effective in MA users is an important public health priority.…”

“…Among baseline light MA users, the probability of achieving a MA-free week was significantly higher in the bupropion condition relative to the placebo condition (OR=2.81, 95% CI=1.61-4.93, p<0.001; Figure 3, panel b), while there was no significant difference between conditions among baseline heavy MA users (OR=0.93, 95% CI=0.24-3.53, p=0.91 for bupropion relative to placebo; Figure 3, panel c). In an additional post hoc analysis replicating the analysis of Elkashef et al (2007), there was no statistically significant effect for bupropion relative to placebo in separate GEE models among participants with baseline heavy MA use (MA use on >18 of the last 30 days) or baseline light MA use (MA use on ≤ 18 of the last 30 days), although the effect for bupropion on a MA-free week among light users was in the predicted direction (OR=1.26, 95%CI 0.77-2.09, p=0.36). The heavy/light user variables defined via baseline urine sample results and baseline self-reported MA use were significantly correlated using Pearson's correlation coefficient (r =0.562, p=0.01).…”

“…A post hoc analysis compared treatment outcomes separately among baseline light MA users, defined as 0-2 of the 6 urine drug screens during the two week baseline/screening period positive for MA-metabolites, and baseline heavy MA users, defined as 3-6 of the 6 urine drug screens during the two week baseline/screening period positive for MA-metabolites. The post hoc analysis comparing potential effects of treatment on urine drug screen results in separate GEE models among baseline heavy versus light MA users was also repeated using selfreported past 30 days MA use to stratify the sample as heavy (MA use on >18 days) versus light (MA use on ≤ 18 days) MA users, as done previously by Elkashef et al (2007). Effect of treatment condition on continuous measures such as the BDI and MA-craving VAS scale were evaluated using a mixed model approach (Singer, 1998) …”

“…To date, no effective pharmacologic treatments for MA addiction have been identified, although results of a recent clinical trial provide preliminary evidence supporting the efficacy of bupropion for reducing MA use among participants with lighter (MA use on 18 or fewer of the past 30 days) but not heavier (MA use on more than 18 of the last 30 days) MA use at baseline (Elkashef et al, 2007). The aim of this study is to evaluate the efficacy of bupropion compared to placebo as a treatment for MA dependence in the presence of evidence-based behavioral therapies, including contingency management and cognitive behavioral therapy.…”