Safety of intravenous methamphetamine administration during treatment with bupropion

Rationale: Methamphetamine dependence is a growing problem for which no medication treatments have proven effective. Objectives: We evaluated bupropion, an antidepressant with beneficial effects for the treatment of nicotine dependence, in patients with methamphetamine dependence, to assess the safety and tolerability of methamphetamine administration during bupropion treatment. Methods: Twenty-six participants entered the study and 20 completed the protocol. Participants received intravenous methamphetamine (0, 15, and 30 mg) before and after randomization to twice-daily bupropion (150 mg SR) or matched placebo. Dependent measures included cardiovascular effects of methamphetamine, methamphetamine and amphetamine pharmacokinetics, and peak and trough plasma concentrations of bupropion and its metabolites. Results: Bupropion treatment was well tolerated, with bupropion- and placebo-treated groups reporting similar rates of adverse events. Methamphetamine administration was associated with expected stimulant cardiovascular effects, and these were not accentuated by bupropion treatment. Instead, there was a trend for bupropion to reduce methamphetamine-associated increases in blood pressure and a statistically significant reduction in methamphetamine-associated increases in heart rate. Pharmacokinetic analysis revealed that bupropion treatment reduced the plasma clearance of methamphetamine and also reduced the appearance of amphetamine in the plasma. Methamphetamine administration did not alter the peak and trough plasma concentrations of bupropion or its metabolites. Conclusions: Methamphetamine administration was well tolerated during bupropion treatment. There was no evidence of additive cardiovascular effects when the drugs were coadministered. This study provides initial evidence for the safety of prescribing bupropion for the treatment of methamphetamine abuse and dependence. The impact of bupropion treatment in patients who abuse larger doses of methamphetamine remains undetermined.