Association of Bupropion, Naltrexone, and Opioid Agonist Treatment With Stimulant-Related Admissions Among People With Opioid Use Disorder: A Case-Crossover Analysis

Kevin Y. Xu, MD, MPH^a,* ; Carrie M. Mintz, MD^a ; Ned Presnall, MSW^a ; Laura J. Bierut, MD^a,b ; Richard A. Grucza, PhD^a,c

J Clin Psychiatry 2022;83(4):21m14112

ABSTRACT

Background: Stimulant use has substantially increased among people with opioid use disorder (OUD) and is associated with worse treatment outcomes. This study’s objective was to compare risk of stimulant-related emergency department (ED) and hospital admissions associated with exposure to bupropion, OUD medication (buprenorphine, naltrexone, and methadone), and selective serotonin reuptake inhibitors (SSRIs; active comparator) relative to days without active prescriptions for medication.

Methods: This recurrent-event, case-crossover study used insurance claims from 51,084 individuals with OUD enrolled in the IBM MarketScan (2006–2016) Databases who had at least 1 stimulant-related ED or hospital admission. Conditional logistic regression models estimated the risk of admissions between days without active prescriptions and days with prescriptions for bupropion, OUD medication, and SSRIs. Secondary analyses were conducted by stimulant subtype (cocaine; amphetamine) and event subtype (falls, injuries, or poisonings; psychotic events).

Results: Compared to days without active prescriptions, days with bupropion treatment were associated with decreased odds of stimulant-related ED or hospital admissions (odds ratio [OR] = 0.77; 95% confidence interval [CI], 0.72–0.82) Among OUD medications, we observed strong protective associations with decreased admissions for buprenorphine (OR = 0.67; 95% CI, 0.64–0.71), naltrexone (OR = 0.65; 95% CI, 0.60–0.70), and methadone (OR = 0.59; 95% CI, 0.51–0.67). The SSRI active comparator group was associated with a small protective association with decreased admissions (OR = 0.90; 95% CI, 0.86–0.93). These effects were sustained in secondary analyses stratifying by stimulant and event subtype.

Conclusions: Bupropion and OUD medication, including both naltrexone and opioid agonists, are associated with fewer stimulant-related ED or hospital admissions in patients with OUD. Bupropion may show promise as adjunctive therapy targeting stimulant-specific poisoning risk.

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References (36)

Ellis MS, Kasper ZA, Cicero TJ. Twin epidemics: the surging rise of methamphetamine use in chronic opioid users. Drug Alcohol Depend. 2018;193:14–20. PubMed CrossRef
Goodwin RD, Moeller SJ, Zhu J, et al. The potential role of cocaine and heroin co-use in the opioid epidemic in the United States. Addict Behav. 2021;113:106680. PubMed CrossRef
Daniulaityte R, Silverstein SM, Crawford TN, et al. Methamphetamine use and its correlates among individuals with opioid use disorder in a Midwestern US city. Subst Use Misuse. 2020;55(11):1781–1789. PubMed CrossRef
McCall Jones C, Baldwin GT, Compton WM. Recent Increases in cocaine-related overdose deaths and the role of opioids. Am J Public Health. 2017;107(3):430–432. PubMed CrossRef
Rodríguez-Cintas L, Daigre C, Grau-López L, et al. Impulsivity and addiction severity in cocaine and opioid dependent patients. Addict Behav. 2016;58:104–109. PubMed CrossRef
The Lancet. Opioids and methamphetamine: a tale of two crises. Lancet. 2018;391(10122):713. PubMed CrossRef
Tsui JI, Mayfield J, Speaker EC, et al. Association between methamphetamine use and retention among patients with opioid use disorders treated with buprenorphine. J Subst Abuse Treat. 2020;109:80–85. PubMed CrossRef
Alexander PD, Gicas KM, Willi TS, et al. A comparison of psychotic symptoms in subjects with methamphetamine versus cocaine dependence. Psychopharmacology (Berl). 2017;234(9-10):1535–1547. PubMed CrossRef
Marshall BD, Werb D. Health outcomes associated with methamphetamine use among young people: a systematic review. Addiction. 2010;105(6):991–1002. PubMed CrossRef
Marzuk PM, Tardiff K, Leon AC, et al. Fatal injuries after cocaine use as a leading cause of death among young adults in New York City. N Engl J Med. 1995;332(26):1753–1757. PubMed CrossRef
Tominaga GT, Garcia G, Dzierba A, et al. Toll of methamphetamine on the trauma system. Arch Surg. 2004;139(8):844–847. PubMed CrossRef
Trivedi MH, Walker R, Ling W, et al. Bupropion and naltrexone in methamphetamine use disorder. N Engl J Med. 2021;384(2):140–153. PubMed CrossRef
Ahmadi J, Razeghian Jahromi L. Comparing the effect of buprenorphine and methadone in the reduction of methamphetamine craving: a randomized clinical trial. Trials. 2017;18(1):259. PubMed CrossRef
Ling W, Hillhouse MP, Saxon AJ, et al. Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. Addiction. 2016;111(8):1416–1427. PubMed CrossRef
Schottenfeld RS, Pakes JR, Oliveto A, et al. Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse. Arch Gen Psychiatry. 1997;54(8):713–720. PubMed CrossRef
Coffin PO, Santos GM, Hern J, et al. Effects of mirtazapine for methamphetamine use disorder among cisgender men and transgender women who have sex with men: a placebo-controlled randomized clinical trial. JAMA Psychiatry. 2020;77(3):246–255. PubMed CrossRef
Siefried KJ, Acheson LS, Lintzeris N, et al. Pharmacological treatment of methamphetamine/amphetamine dependence: a systematic review. CNS Drugs. 2020;34(4):337–365. PubMed CrossRef
Allison P, Christakis N. Fixed-effects methods for the analysis of nonrepeated events. Sociol Methodol. 2006;36(1):155–172. CrossRef
Xu KY, Borodovsky JT, Presnall N, et al. Association between benzodiazepine or z-drug prescriptions and drug-related poisonings among patients receiving buprenorphine maintenance: a case-crossover analysis. Am J Psychiatry. 2021;178(7):651–659. PubMed CrossRef
Xu KY, Presnall N, Mintz CM, et al. Association of opioid use disorder treatment with alcohol-related acute events. JAMA Netw Open. 2021;4(2):e210061. PubMed CrossRef
Adamson DM, Chang S, Hansen LG. Health Research Data for the Real World: The MarketScan Databases. MedStat; 2006.
Fiellin DA, Weiss L, Botsko M, et al; BHIVES Collaborative. Drug treatment outcomes among HIV-infected opioid-dependent patients receiving buprenorphine/naloxone. J Acquir Immune Defic Syndr. 2011;56(suppl 1):S33–S38. PubMed CrossRef
Salehi M, Emadossadat A, Kheirabadi GR, et al. The effect of buprenorphine on methamphetamine cravings. J Clin Psychopharmacol. 2015;35(6):724–727. PubMed CrossRef
Darke S, Kaye S, Duflou J. Rates, characteristics and circumstances of methamphetamine-related death in Australia: a national 7-year study. Addiction. 2017;112(12):2191–2201. PubMed CrossRef
Degenhardt L, Sara G, McKetin R, et al. Crystalline methamphetamine use and methamphetamine-related harms in Australia. Drug Alcohol Rev. 2017;36(2):160–170. PubMed CrossRef
Grant KM, LeVan TD, Wells SM, et al. Methamphetamine-associated psychosis. J Neuroimmune Pharmacol. 2012;7(1):113–139. PubMed CrossRef
Zweben JE, Cohen JB, Christian D, et al; Methamphetamine Treatment Project. Psychiatric symptoms in methamphetamine users. Am J Addict. 2004;13(2):181–190. PubMed CrossRef
Michel L, Des Jarlais DC, Duong Thi H, et al; DRIVE Study Team. Intravenous heroin use in Haiphong, Vietnam: Need for comprehensive care including methamphetamine use-related interventions. Drug Alcohol Depend. 2017;179:198–204. PubMed CrossRef
Deck D, Carlson MJ. Access to publicly funded methadone maintenance treatment in two western states. J Behav Health Serv Res. 2004;31(2):164–177. PubMed CrossRef
Morgan JR, Schackman BR, Weinstein ZM, et al. Overdose following initiation of naltrexone and buprenorphine medication treatment for opioid use disorder in a United States commercially insured cohort. Drug Alcohol Depend. 2019;200:34–39. PubMed CrossRef
Kinsky S, Houck PR, Mayes K, et al. A comparison of adherence, outcomes, and costs among opioid use disorder Medicaid patients treated with buprenorphine and methadone: A view from the payer perspective. J Subst Abuse Treat. 2019;104:15–21. PubMed CrossRef
Lee JD, Nunes EV Jr, Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018;391(10118):309–318. PubMed CrossRef
Philbin MM, Greene ER, Martins SS, et al. Medical, nonmedical, and illegal stimulant use by sexual identity and gender. Am J Prev Med. 2020;59(5):686–696. PubMed CrossRef
Hagle HN, Martin M, Winograd R, et al. Dismantling racism against black, indigenous, and people of color across the substance use continuum: a position statement of the association for multidisciplinary education and research in substance use and addiction. Subst Abus. 2021;42(1):5–12. PubMed CrossRef
Barocas JA. Commentary on Jones et al. (2020): using indirect estimation methods of drug use prevalence to address racial and ethnic health disparities. Addiction. 2020;115(12):2405–2406. PubMed CrossRef
Jones HE, Harris RJ, Downing BC, et al. Estimating the prevalence of problem drug use from drug-related mortality data. Addiction. 2020;115(12):2393–2404. PubMed CrossRef