BACKGROUND: There has been a significant increase in methamphetamine use and methamphetamine use disorder (Meth UD) in the United States, with evolving racial and ethnic differences. OBJECTIVES: This secondary analysis explored racial and ethnic differences in baseline sociodemographic and clinical characteristics as well as treatment effects on a measure of substance use recovery, depression symptoms, and methamphetamine craving among participants in a pharmacotherapy trial for Meth UD. METHODS: The ADAPT-2 trial (ClinicalTrials.gov number, NCT03078075; N=403; 69% male) was a multisite, 12-week randomized, double-blind, trial that employed a two-stage sequential parallel design to evaluate the efficacy of combination naltrexone (NTX) and oral bupropion (BUP) vs. placebo for Meth UD. Treatment effect was calculated as the weighted mean change in outcomes in the NTX-BUP minus placebo group across the two stages of treatment. RESULTS: Of the 403 participants in the ADAPT-2 trial, the majority (65%) reported non-Hispanic White, while 14%, 11% and 10% reported Hispanic, non-Hispanic Black, and non-Hispanic other racial and ethnic categories respectively. At baseline non-Hispanic Black participants reported less severe indicators of methamphetamine use than non-Hispanic White. Treatment effects for recovery, depression symptoms and methamphetamine cravings did not significantly differ by race and ethnicity. CONCLUSIONS: Although we found racial and ethnic differences at baseline, our findings did not show racial and ethnic differences in treatment effects of NTX-BUP on recovery, depression symptoms and methamphetamine cravings. However, our findings also highlight the need to expand representation of racial and ethnic minority groups in future trials.

Background

The co-occurrence of suicidality and substance use disorders has been well established, but rating scales to examine suicidal behavior and risk are sparse among participants with substance use disorders. We examined the psychometric properties of the 16-item Concise Health Risk Tracking Scale - Self Report (CHRT-SR₁₆) to measure suicidality among adults with moderate-to-severe methamphetamine use disorder.

Methods

Participants (n = 403) with moderate-to-severe methamphetamine use disorder completed the CHRT-SR₁₆ as part of a randomized, double-blind, placebo-controlled pharmacotherapy trial. The CHRT-SR₁₆ factor structure was assessed using confirmatory factor analysis (CFA). Internal consistency was estimated with coefficients alpha (α) and omega (ω), test-retest reliability with intraclass correlation coefficient (ICC) and standard error of measurement, and convergent validity using Spearman's ρ rank order correlation coefficient test between CHRT-SR₁₆ factors and the Patient Health Questionnaire (PHQ-9). The analyses utilized baseline and week 1 data (for test-retest reliability only).

Results

CFA revealed a seven-factor model of Pessimism, Helplessness, Social Support, Despair, Impulsivity, Irritability, and Suicidal Thoughts as the best-fitting model. The CHRT-SR₁₆ also exhibited strong internal consistency (α = 0.89; ω = 0.89), test-retest reliability (ICC = 0.78) and convergent validity with the PHQ-9 total score (ρ = 0.62).

Conclusion

The CHRT-SR₁₆ showed strong psychometric properties in a sample of participants with primary methamphetamine use disorder.

Clinicaltrialsgov identifier

NCT03078075.

Background

The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.

Methods

We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses.

Results

A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial.

Conclusions

Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).