1. ¹Clinical Medical Branch, Division of Pharmacotherapies and Medical Consequences, National Institutes of Health, National Institute on Drug Abuse, Bethesda, MD, USA
2. ²Department of Psychiatry, Integrated Substance Abuse Programs, University of California, Los Angeles, Los Angeles, CA, USA
3. ³Division of Biostatistics, Department of Health Research and Policy, School of Medicine, Stanford University, Stanford, CA, USA
4. ⁴Department of Psychiatry, Matrix Institute on Addictions, Costa Mesa, CA, USA
5. ⁵Department of Psychiatry, University of Missouri, Kansas City, MO, USA
6. ⁶Department of Psychiatry, Quintiles Inc., Kansas City, MO, USA
7. ⁷John A. Burns School of Medicine, Department of Psychiatry, University of Hawaii, Honolulu, HI, USA
8. ⁸South Bay Treatment Center, San Diego, CA, USA
9. ⁹Department of Addiction Medicine, Lutheran Hospital, Powell Addiction Research Center, Des Moines, IA, USA

Correspondence: Dr AM Elkashef, NIH, Medications Development Division, National Institute on Drug Abuse, DPMC, Neuroscience Bldg, 6001 Executive Blvd., Rm-4151, Bethesda, MD, USA. Tel: +1 301 443 5055; Fax: +1 301 443 2599; E-mail: ae8a@nih.gov

Received 3 April 2007; Revised 11 May 2007; Accepted 17 May 2007; Published online 20 June 2007.

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=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 (p<0.0001). 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.