Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

© 2020 The Author(s). Background: The risks of harms from opioids increase substantially at high doses, and high-dose prescribing has increased in primary care. However, little is known about what leads to high-dose prescribing, and studies exploring this have not been synthesized. We, therefore, systematically synthesized factors associated with the prescribing of high-dose opioids in primary care. Methods: We conducted a systematic review of observational studies in high-income countries that used patient-level primary care data and explored any factor(s) in people for whom opioids were prescribed, stratified by oral morphine equivalents (OME). We defined high doses as ≥ 90 OME mg/day. We searched MEDLINE, Embase, Web of Science, reference lists, forward citations, and conference proceedings from database inception to 5 April 2019. Two investigators independently screened studies, extracted data, and appraised the quality of included studies using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. We pooled data on factors using random effects meta-Analyses and reported relative risks (RR) or mean differences with 95% confidence intervals (CI) where appropriate. We also performed a number needed to harm (NNTH) calculation on factors when applicable. Results: We included six studies with a total of 4,248,119 participants taking opioids, of whom 3.64% (n = 154,749) were taking high doses. The majority of included studies (n = 4) were conducted in the USA, one in Australia and one in the UK. The largest study (n = 4,046,275) was from the USA. Included studies were graded as having fair to good quality evidence. The co-prescription of benzodiazepines (RR 3.27, 95% CI 1.32 to 8.13, I 2 = 99.9%), depression (RR 1.38, 95% CI 1.27 to 1.51, I 2 = 0%), emergency department visits (RR 1.53, 95% CI 1.46 to 1.61, I 2 = 0%, NNTH 15, 95% CI 12 to 20), unemployment (RR 1.44, 95% CI 1.27 to 1.63, I 2 = 0%), and male gender (RR 1.21, 95% CI 1.14 to 1.28, I 2 = 78.6%) were significantly associated with the prescribing of high-dose opioids in primary care. Conclusions: High doses of opioids are associated with greater risks of harms. Associated factors such as the co-prescription of benzodiazepines and depression identify priority areas that should be considered when selecting, identifying, and managing people taking high-dose opioids in primary care. Coordinated strategies and services that promote the safe prescribing of opioids are needed. Study registration: PROSPERO, CRD42018088057

Original publication




Journal article


BMC Medicine

Publication Date