A 2015 randomized trial tested a plausible hypothesis: bupropion might improve abstinence among people using methamphetamine less than daily. The primary result did not support that benefit. Medication adherence was low, but that limitation does not convert the negative comparison into evidence that the drug worked in an unobserved fully adherent population.
Why select non-daily users?
Earlier findings had suggested possible benefit in a lower-frequency subgroup. Anderson and colleagues therefore recruited treatment-seeking adults with methamphetamine dependence who reported use on no more than 29 of the 30 days before consent. “Non-daily” covered a wide range of patterns; it did not mean only occasional exposure.
The analysis included 204 randomized participants who took a first dose: 100 assigned oral sustained-release bupropion, 150 mg twice daily, and 104 assigned matching placebo. Treatment lasted twelve weeks, followed by four weeks of follow-up. Participants also received frequent clinic visits and group relapse-prevention therapy. This was a medication-plus-services comparison against placebo-plus-services.
What counted as abstinence?
The primary endpoint required at least two urine specimens in each of weeks 11 and 12, with every specimen in those weeks negative under the study’s methamphetamine rule. Dropping out before the terminal assessment counted as failure. This is a specific terminal-abstinence endpoint, not a claim of continuous abstinence throughout all twelve weeks.
Urine immunoassay used a 300 ng/mL decision level for methamphetamine and/or amphetamine, with positive screens followed by gas chromatography–mass spectrometry. The reported confirmatory methamphetamine quantification limit was 78 ng/mL. An analytical quantification limit and the endpoint’s 300 ng/mL classification rule served different purposes; neither was a blood impairment threshold.
What did the trial find?
Terminal abstinence occurred in 14/100 bupropion participants and 20/104 placebo participants, approximately 14% versus 19% (p=0.32). Twelve-week completion was 57% in each group. The study did not demonstrate either an abstinence or retention advantage.
Among participants reporting use on no more than 18 of the previous 30 days, success was 13/65 with bupropion and 17/76 with placebo (p=0.73). Lower baseline use predicted better outcomes when groups were combined. That prognostic association is different from evidence that lower-frequency users specifically benefited from bupropion.
What does the adherence assay add?
The researchers measured bupropion in urine, using a 5 ng/mL lower quantification limit. Their adherence rule required detectable medication in specified proportions of specimens during earlier and terminal treatment weeks. Only 47/100 active participants met it. No corresponding biochemical marker measured placebo adherence.
Low exposure to assigned medication can dilute an intention-to-treat treatment effect. But selecting adherent participants afterward also selects for attendance, motivation, stability and other factors related to outcome. Without a comparable control strategy, better outcomes among selected adherent people cannot be attributed solely to medication.
What uncertainty remains?
Recruitment criteria were relaxed during the study to permit corroborated use without a positive screening urine. Some participants consequently had no positive urine throughout screening or treatment. Attrition, greater-than-expected placebo success and imperfect adherence reduced the study’s ability to detect some benefits.
Bupropion was discontinued for several adverse events, including two seizures; one occurred after a participant stopped an undisclosed anticonvulsant. These observations require context rather than a claim that every event had a single cause. The historical evidence supports neither an established abstinence benefit nor a categorical conclusion that bupropion could never help under different conditions.
Source
Anderson AL, Li SH, Markova D, et al. Bupropion for the Treatment of Methamphetamine Dependence in Non-Daily Users: a Randomized, Double-Blind, Placebo-Controlled Trial. Drug and Alcohol Dependence. 2015;150:170–174. doi:10.1016/j.drugalcdep.2015.01.036.
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