A gender-based secondary analysis of the ADAPT-2 combination naltrexone and bupropion treatment for methamphetamine use disorder trial

Ximena A. Levander, Thomas Carmody, Ryan R. Cook, Jennifer S. Potter, Madhukar H. Trivedi, Philip Todd Korthuis, Steven Shoptaw

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background and Aims: Socio-cultural (gender) and biological (sex)-based differences contribute to psychostimulant susceptibility, potentially affecting treatment responsiveness among women with methamphetamine use disorder (MUD). The aims were to measure (i) how women with MUD independently and compared with men respond to treatment versus placebo and (ii) among women, how the hormonal method of contraception (HMC) affects treatment responsiveness. Design: This was a secondary analysis of ADAPT-2, a randomized, double-blind, placebo-controlled, multicenter, two-stage sequential parallel comparison design trial. Setting: United States. Participants: This study comprised 126 women (403 total participants); average age = 40.1 years (standard deviation = 9.6) with moderate to severe MUD. Interventions: Interventions were combination intramuscular naltrexone (380 mg/3 weeks) and oral bupropion (450 mg daily) versus placebo. Measurements: Treatment response was measured using a minimum of three of four negative methamphetamine urine drug tests during the last 2 weeks of each stage; treatment effect was the difference between weighted treatment responses of each stage. Findings: At baseline, women used methamphetamine intravenously fewer days than men [15.4 versus 23.1% days, P = 0.050, difference = −7.7, 95% confidence interval (CI) = −15.0 to −0.3] and more women than men had anxiety (59.5 versus 47.6%, P = 0.027, difference = 11.9%, 95% CI = 1.5 to 22.3%). Of 113 (89.7%) women capable of pregnancy, 31 (27.4%) used HMC. In Stage 1 29% and Stage 2 5.6% of women on treatment had a response compared with 3.2% and 0% on placebo, respectively. A treatment effect was found independently for females and males (P < 0.001); with no between-gender treatment effect (0.144 females versus 0.100 males; P = 0.363, difference = 0.044, 95% CI = −0.050 to 0.137). Treatment effect did not differ by HMC use (0.156 HMC versus 0.128 none; P = 0.769, difference = 0.028, 95% CI −0.157 to 0.212). Conclusions: Women with methamphetamine use disorder receiving combined intramuscular naltrexone and oral bupropion treatment achieve greater treatment response than placebo. Treatment effect does not differ by HMC.

Original languageEnglish (US)
Pages (from-to)1320-1328
Number of pages9
Issue number7
StatePublished - Jul 2023


  • Amphetamine-related disorders
  • bupropion
  • clinical trial
  • gender differences
  • methamphetamine
  • naltrexone
  • sex differences
  • women
  • women's health

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health


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