title: Safety of intravenous methamphetamine administration during treatment with bupropion.
abstract: BACKGROUND
  Methamphetamine dependence is a growing problem for which no medication treatments have proven effective.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. tnewton@mednet.ucla.edu
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Newton
authors.forename: John D
authors.initials: JD
authors.lastname: Roache
authors.forename: Richard
authors.initials: R
authors.lastname: De La Garza
authors.forename: Tim
authors.initials: T
authors.lastname: Fong
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wallace
authors.forename: Shou-Hua
authors.initials: SH
authors.lastname: Li
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elkashef
authors.forename: Nora
authors.initials: N
authors.lastname: Chiang
authors.forename: Roberta
authors.initials: R
authors.lastname: Kahn
mesh_terms: D000293:Adolescent; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D016642:Bupropion / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects* / Q000493:pharmacokinetics; D008875:Middle Aged
chemical_list: D016642:Bupropion; D008694:Methamphetamine