Research News

Research News — Faculty from the addiction medicine fellowships at Boston University, Swedish Medical Center and MultiCare Good Samaritan Hospital are among the authors on two new studies regarding treatment for opioid use disorder:

  • “Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study” was electronically published ahead of print on June 19 by the Annals of Internal Medicine. Its authors include Alex Walley, MD, MSc, Program Director of the Boston University fellowship, and Sarah Bagley, MD, MSc, a graduate and current faculty member of the fellowship. (The study was funded by the NIH, and NIDA Director Nora Volkow, MD, co-authored an accompanying editorial on its significance)
  • “Does Maternal Buprenorphine Dose Affect Severity or Incidence of Neonatal Abstinence Syndrome?” was electronically published ahead of print on June 13 by the Journal of Addiction Medicine. Its authors include Swedish Medical Center faculty Jacqueline Wong, MD, James Walsh, MD (Program Director), Vania Rudolf, MD, MPH, and Paul Gianutsos, MD, MPH, along with Abigail Plawman, MD, Program Director of the MultiCare fellowship, and David Sapienza, MD, a fellowship graduate.

Study citations and abstracts:

Larochelle MR, Bernson D, Land T, Stopka TJ, Wang N, Xuan Z, Bagley SM, Liebschutz JM, Walley AY. Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study. Annals of Internal Medicine. 2018.

BACKGROUND: Opioid overdose survivors have an increased risk for death. Whether use of medications for opioid use disorder (MOUD) after overdose is associated with mortality is not known.

OBJECTIVE: To identify MOUD use after opioid overdose and its association with all-cause and opioid-related mortality.

DESIGN: Retrospective cohort study. Setting: 7 individually linked data sets from Massachusetts government agencies. Participants: 17 568 Massachusetts adults without cancer who survived an opioid overdose between 2012 and 2014. Measurements: Three types of MOUD were examined: methadone maintenance treatment (MMT), buprenorphine, and naltrexone. Exposure to MOUD was identified at monthly intervals, and persons were considered exposed through the month after last receipt. A multivariable Cox proportional hazards model was used to examine MOUD as a monthly time-varying exposure variable to predict time to all-cause and opioid-related mortality.

RESULTS: In the 12 months after a nonfatal overdose, 2040 persons (11%) enrolled in MMT for a median of 5 months (interquartile range, 2 to 9 months), 3022 persons (17%) received buprenorphine for a median of 4 months (interquartile range, 2 to 8 months), and 1099 persons (6%) received naltrexone for a median of 1 month (interquartile range, 1 to 2 months). Among the entire cohort, all-cause mortality was 4.7 deaths (95% CI, 4.4 to 5.0 deaths) per 100 person-years and opioid-related mortality was 2.1 deaths (CI, 1.9 to 2.4 deaths) per 100 person-years. Compared with no MOUD, MMT was associated with decreased all-cause mortality (adjusted hazard ratio [AHR], 0.47 [CI, 0.32 to 0.71]) and opioid-related mortality (AHR, 0.41 [CI, 0.24 to 0.70]). Buprenorphine was associated with decreased all-cause mortality (AHR, 0.63 [CI, 0.46 to 0.87]) and opioid-related mortality (AHR, 0.62 [CI, 0.41 to 0.92]). No associations between naltrexone and all-cause mortality (AHR, 1.44 [CI, 0.84 to 2.46]) or opioid-related mortality (AHR, 1.42 [CI, 0.73 to 2.79]) were identified. Limitation: Few events among naltrexone recipients preclude confident conclusions.

CONCLUSION: A minority of opioid overdose survivors received MOUD. Buprenorphine and MMT were associated with reduced all-cause and opioid-related mortality.

Wong J, Saver B, Scanlan JM, Gianutsos LP, Bhakta Y, Walsh J, Plawman A, Sapienza D, Rudolf V. Does Maternal Buprenorphine Dose Affect Severity or Incidence of Neonatal Abstinence Syndrome? Journal of Addiction Medicine. 2018.

OBJECTIVES: To measure the incidence, onset, duration, and severity of neonatal abstinence syndrome (NAS) in infants born to mothers receiving buprenorphine and to assess the association between buprenorphine dose and NAS outcomes.

METHODS: We reviewed charts of all mother-infant pairs maintained on buprenorphine who delivered in our hospital from January 1, 2000 to April 1, 2016.

RESULTS: In 89 infants, NAS incidence requiring morphine was 43.8%. Means for morphine-treated infants included: 55.2 hours to morphine start, 15.9 days on morphine, and 20 days hospital stay. NAS requiring morphine treatment occurred in 48.5% and 41.4% of infants of mothers receiving </=8 mg/d buprenorphine versus >8 mg/d, respectively (P = 0.39). We found no significant associations of maternal buprenorphine dose with peak NAS score, NAS severity requiring morphine, time to morphine start, peak morphine dose, or days on morphine. Among the other factors examined, only exclusive breastfeeding was significantly associated with neonatal outcomes, specifically lower odds of morphine treatment (odds ratio 0.24, P = 0.003).            CONCLUSIONS: These findings suggest higher buprenorphine doses can be prescribed to pregnant women receiving medication therapy for addiction without increasing NAS severity. Our finding of reduced risk of NAS requiring morphine treatment also suggests breastfeeding is both safe and beneficial for these infants and should be encouraged.