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
{"title":"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","authors":"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","doi":"10.4088/JCP.25m15825","DOIUrl":null,"url":null,"abstract":"<p><p><b>Objective:</b> 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.</p><p><p><b>Methods:</b> 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.</p><p><p><b>Results:</b> 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.</p><p><p><b>Conclusion:</b> 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.</p><p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT03078075.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 3","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Early Change in Depressive Symptom Severity With Naltrexone-Bupropion Combination and Its Association With Reduction in Methamphetamine Use in ADAPT-2 Trial.\",\"authors\":\"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\",\"doi\":\"10.4088/JCP.25m15825\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Objective:</b> 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.</p><p><p><b>Methods:</b> 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.</p><p><p><b>Results:</b> 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.</p><p><p><b>Conclusion:</b> 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.</p><p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT03078075.</p>\",\"PeriodicalId\":50234,\"journal\":{\"name\":\"Journal of Clinical Psychiatry\",\"volume\":\"86 3\",\"pages\":\"\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-07-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4088/JCP.25m15825\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4088/JCP.25m15825","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Early Change in Depressive Symptom Severity With Naltrexone-Bupropion Combination and Its Association With Reduction in Methamphetamine Use in ADAPT-2 Trial.
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.
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.
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