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

IF 4.6 2区医学 Q1 PSYCHIATRY

Journal of Clinical Psychiatry Pub Date : 2025-07-30 DOI:10.4088/JCP.25m15825

Manish K Jha, Udi E Ghitza, Steve Shoptaw, Abu Minhajuddin, Snoben Kuruvila, Sidarth Wakhlu, Edward V Nunes, Joy Schmitz, Phillip O Coffin, Gavin Bart, Thomas Carmody, Madhukar H Trivedi

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引用次数: 0

Abstract

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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在ADAPT-2试验中，纳曲酮-安非他酮联合用药对抑郁症状严重程度的早期改变及其与甲基苯丙胺使用减少的关系

目的：本研究评估与安慰剂相比，缓释纳曲酮和安非他酮联合使用（纳曲酮安非他酮）是否能早期改善中度/重度甲基苯丙胺使用障碍患者的抑郁症状严重程度，并预测随后的甲基苯丙胺使用。方法：对甲基苯丙胺使用障碍添加剂药物治疗加速开发（ADAPT-2）试验的二次分析，该试验于2017年5月23日至2019年7月25日进行，包括326名患者，9项患者健康问卷（PHQ-9）基线评分≥5分。重复测量混合模型分析评估了纳曲酮-安非他酮与安慰剂在抑郁症状严重程度上的早期（基线至第4周）变化，并提供了PHQ-9变化的斜率估计。其他抑郁结局包括缓解（PHQ-9较基线降低≥50%）和缓解（PHQ-9≤4）。如果在第5周和第6周，4次尿药物筛查中有3次为阴性，则认为甲基苯丙胺治疗有反应。Logistic回归分析评估抑郁症的变化是否能预测甲基苯丙胺治疗的反应。协变量包括年龄、性别、种族、民族和基线PHQ-9。结果：与安慰剂相比，纳曲酮-安非他酮组在第4周PHQ-9评分的降低幅度更大(估计= -2.52；标准误差= 0.81)。在第4周，抑郁反应(优势比[OR] = 2.54；95%置信限[CL]， 1.42-4.55)和缓解(OR = 3.04；95% CL(1.57-5.87)，纳曲酮-安非他酮组比安慰剂组更有可能。基线至第4周PHQ-9降低幅度越大，甲基苯丙胺治疗反应的可能性越高（OR = 3.74, 95% CL, 1.28-10.93），这解释了24.8% （95% CI, 6.7%-60.3%）的纳曲酮-安非他酮对甲基苯丙胺治疗反应的影响。结论：与安慰剂相比，纳曲酮安非他酮的使用与抑郁症状严重程度的早期减轻有关，后者与随后甲基苯丙胺使用减少的可能性更高有关。试验注册：ClinicalTrials.gov标识符：NCT03078075。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Psychiatry 医学-精神病学

CiteScore

7.40

自引率

1.90%

发文量

审稿时长

3-8 weeks

期刊介绍： For over 75 years, The Journal of Clinical Psychiatry has been a leading source of peer-reviewed articles offering the latest information on mental health topics to psychiatrists and other medical professionals.The Journal of Clinical Psychiatry is the leading psychiatric resource for clinical information and covers disorders including depression, bipolar disorder, schizophrenia, anxiety, addiction, posttraumatic stress disorder, and attention-deficit/hyperactivity disorder while exploring the newest advances in diagnosis and treatment.