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September 10, 2025

Early Change in Depressive Symptom Severity With Naltrexone-Bupropion Combination and Its Association With Reduction in Methamphetamine Use in ADAPT-2 Trial

Puntos clave

Early use of naltrexone-bupropion led to a greater reduction in depressive symptoms, enhancing recovery chances.
At week 4, patients receiving naltrexone-bupropion exhibited a significant odds ratio of 2.54 for depression response compared to placebo.
Logistic regression analysis indicated improved depressive symptoms were significantly associated with enhanced likelihood of successful methamphetamine treatment responses.
Findings suggest that targeting depressive symptoms can play a crucial role in treating methamphetamine use disorder.

Resumen

Objective: This study evaluated whether depressive symptom severity improved early with extended-release naltrexone and bupropion combination (naltrexone bupropion) compared to a placebo in individuals with moderate/severe methamphetamine use disorder and predicted subsequent use of methamphetamine. Methods: This secondary analysis from the Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT-2) trial, which was conducted from May 23, 2017-July 25, 2019, included 326 individuals with a 9-item Patient Health Questionnaire (PHQ-9) score ≥5 at baseline. Repeated-measures mixed model analyses evaluated early (baseline-to-week-4) changes in depressive symptom severity with naltrexone-bupropion versus placebo and provided slope estimates for PHQ-9 change. Additional depression outcomes included response (≥50% reduction in PHQ-9 from baseline) and remission (PHQ-9 ≤4). Methamphetamine treatment response was ascribed if 3 out of 4 urine drug screens were negative during weeks 5 and 6. Logistic regression analyses evaluated whether changes in depression predicted methamphetamine treatment response. Covariates included age, sex, race, ethnicity, and baseline PHQ-9. Results: There was a greater reduction in PHQ-9 scores at week 4 with naltrexone-bupropion versus placebo (estimate = -2.52; standard error = 0.81). At week 4, depression response (odds ratio OR = 2.54; 95% confidence limit CL, 1.42-4.55) and remission (OR = 3.04; 95% CL, 1.57-5.87) were more likely with naltrexone-bupropion versus placebo. Greater baseline-to-week 4 reduction in PHQ-9 was associated with a higher likelihood of methamphetamine treatment response (OR = 3.74, 95% CL, 1.28-10.93) and explained 24.8% (95% CI, 6.7%-60.3%) of the effect of naltrexone-bupropion on methamphetamine treatment response. Conclusion: Use of naltrexone bupropion was associated with early reduction in depressive symptom severity compared to a placebo, which was associated with a higher likelihood of reduction in subsequent methamphetamine use. Trial Registration: ClinicalTrials.gov identifier: NCT03078075.

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Cite This Study

Jha et al. (Wed,) studied this question.

synapsesocial.com/papers/68c1a5e554b1d3bfb60df153 https://doi.org/https://doi.org/10.4088/jcp.25m15825

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