title: Utilizing a Two-stage Design to Investigate the Safety and Potential Efficacy of Monthly Naltrexone Plus Once-daily Bupropion as a Treatment for Methamphetamine Use Disorder.
abstract: This 2-stage open-label pilot study evaluated the safety and potential efficacy of naltrexone + bupropion as a pharmacotherapy for methamphetamine (MA) use disorder.
  
  
  
  The study was conducted in 2 stages of recruitment across 3 sites; 20 participants were enrolled in stage 1 and 29 participants were enrolled in stage 2. Eight weeks of open-label pharmacotherapy with a combination of extended-release injectable naltrexone (XR-NTX; Vivitrol) plus extended-release oral bupropion (BRP; Wellbutrin XL) were provided with a smartphone-assisted medication adherence platform. Participants met Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria for severe MA use disorder, self-reported ≥20 days of MA use in the 30 days prior to consent, and submitted 3 MA-positive urine drug screens (UDS) out of 4 collected during screening. Participants attended clinic twice weekly for observed BRP dosing, UDS testing, assessments, and medical management; XR-NTX was administered at weeks 1 and 5. A BRP taper and follow-up visit occurred in week 9.
  
  
  
  Analyses evaluated effects of XR-NTX + BRP to determine the number of "responders" according to a statistically predefined response criterion (6 of 8 MA-negative UDS during the last 4 weeks of medication). The 2-stage design required that stage 1 yield ≥3 responders to continue to stage 2; 11 of the 49 participants met responder criteria across both stages (5 in stage 1, 6 in stage 2).
  
  
  
  Under the statistical analysis plan, study "success" required ≥9 responders. With 11 responders, the study demonstrated sufficient potential of naltrexone plus bupropion as a combination pharmacotherapy for MA use disorder to warrant further study.
authors.affiliation: University of California (LJM, MPH, CT, AA, GT, WL), Los Angeles, Los Angeles, CA; Emmes (GS, DC), Rockville, MD; University of Hawaii and the Queen's Medical Center (LC), Honolulu, HI; University of Texas Southwestern Medical Center (RW, MT), Dallas, TX; and National Institute on Drug Abuse (SS), Bethesda, MD.
authors.forename: Larissa J
authors.initials: LJ
authors.lastname: Mooney
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Hillhouse
authors.forename: Christie
authors.initials: C
authors.lastname: Thomas
authors.forename: Alfonso
authors.initials: A
authors.lastname: Ang
authors.forename: Gaurav
authors.initials: G
authors.lastname: Sharma
authors.forename: Garth
authors.initials: G
authors.lastname: Terry
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.forename: Robrina
authors.initials: R
authors.lastname: Walker
authors.forename: Madhukar
authors.initials: M
authors.lastname: Trivedi
authors.forename: David
authors.initials: D
authors.lastname: Croteau
authors.forename: Steven
authors.initials: S
authors.lastname: Sparenborg
authors.forename: Walter
authors.initials: W
authors.lastname: Ling
mesh_terms: D000328:Adult; D000368:Aged; D019969:Amphetamine-Related Disorders / Q000188:drug therapy*; D016642:Bupropion / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D016642:Bupropion; D008694:Methamphetamine; D009271:Naltrexone