The impact of buprenorphine and methadone on mortality: a primary care cohort study in the United Kingdom

Abstract

AimsTo estimate whether opioid substitution treatment (OST) with buprenorphine or methadone is associated with a greater reduction in the risk of all‐cause mortality (ACM) and opioid drug‐related poisoning (DRP) mortality.DesignCohort study with linkage between clinical records from Clinical Practice Research Datalink and mortality register.SettingUK primary care.ParticipantsA total of 11 033 opioid‐dependent patients who received OST from 1998 to 2014, followed‐up for 30 410 person‐years.MeasurementsExposure to methadone (17 373, 61%) OST episodes or buprenorphine (9173, 39%) OST episodes. ACM was available for all patients; information on cause of death and DRP was available for 5935 patients (54%) followed‐up for 16 363 person‐years. Poisson regression modelled mortality by treatment period with an interaction between OST type and treatment period (first 4 weeks on OST, rest of time off OST, first 4 weeks off OST, rest of time out of OST censored at 12 months) to test whether ACM or DRP differed between methadone and buprenorphine. Inverse probability weights were included to adjust for confounding and balance characteristics of patients prescribed methadone or buprenorphine.FindingsACM and DRP rates were 1.93 and 0.53 per 100 person‐years, respectively. DRP was elevated during the first 4 weeks of OST [incidence rate ratio (IRR) = 1.93 95% confidence interval (CI) = 0.97–3.82], the first 4 weeks off OST (IRR = 8.15, 95% CI = 5.45–12.19) and the rest of time out of OST (IRR = 2.13, 95% CI = 1.47–3.09) compared with mortality risk from 4 weeks to end of treatment. Patients on buprenorphine compared with methadone had lower ACM rates in each treatment period. After adjustment, there was evidence of a lower DRP risk for patients on buprenorphine compared with methadone at treatment initiation (IRR = 0.08, 95% CI = 0.01–0.48) and rest of time on treatment (IRR = 0.37, 95% CI = 0.17–0.79). Treatment duration (mean and median) was shorter on buprenorphine than methadone (173 and 40 versus 363 and 111, respectively). Model estimates suggest that there was a low probability that methadone or buprenorphine reduced the number of DRP in the population: 28 and 21%, respectively.ConclusionsIn UK general medical practice, opioid substitution treatment with buprenorphine is associated with a lower risk of all‐cause and drug‐related poisoning mortality than methadone. In the population, buprenorphine is unlikely to give greater overall protection because of the relatively shorter duration of treatment.

Impaired frontostriatal functional connectivity among chronic opioid using pain patients is associated with dysregulated affect

“…Long‐term use and misuse of opioids in the context of chronic pain may dysregulate affective processes, significantly elevating risk of opioid use disorder (OUD) and overdose‐related mortality and morbidity . Although current first line U.S. Food and Drug Administration (FDA)‐approved medication‐assisted treatments effectively attenuate withdrawal symptom severity (eg, Buprenorphine and Methadone), it remains questionable as to whether or not they treat the underlying neuropathology of OUD, as evidenced by greater than 50% of participants relapsing after discontinuing opioid maintenance therapy . Therefore, further mechanistic research on prolonged opioid use among individuals with and without chronic pain is needed to elucidate neurobiological mechanisms to be targeted by new treatment approaches.…”

The impact of opiate substitution treatment on mortality risk in drug addicts: a natural experiment study

“…Adjusted results are similar to unadjusted results, suggesting that matching had reduced observed confounding below any level of practical significance. A comparison of PSM results with confounder and IPW adjusted results in the main paper 61 showed similar effects in terms of the point estimates. However, the CIs for PSM results were wider.…”

“…This chapter, on WP 2, presents the results comparing buprenorphine and methadone on mortality. The main report is published in Hickman et al 61 Reproduced from Hickman et al 61 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.…”

“…These mortality ratios compare the observed mortality risk in patients undergoing OST with the assumed mortality risk of opioid-dependent patients who do not enter OST (accounting for fluctuating mortality risk in different periods on and off OST, and for variation in the duration of current treatment). We also estimated the minimum duration of methadone and buprenorphine required to reduce DRP deaths in the population (for more details see web appendix 2 in that WP's main report 61 ).…”

Why Are Early Career Family Physicians Driving Increases in Buprenorphine Prescribing?

“…1 Medicationassisted treatment with either methadone or buprenorphine has been shown in numerous highquality trials to decrease mortality, largely due to a significant reduction in fatal overdose. 2,3 Despite these clear patient-centered benefits, only 10.6% of patients with opioid use disorder are on medication-assisted treatment. 4 Family physicians are solidly positioned to provide this treatment due to their broad scope of care and geographic distribution across the country.…”