Safety of opioids for non-cancer pain

Thesis (Ph.D.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.While the use of opioids for chronic non-cancer pain has increased dramatically in the past 20 years, concern exists for safety of opioid analgesics, particularly for longterm use. Using a matched, nested case-control study design, this dissertation evaluates the safety of opioid treatment among non-cancer adults aged 18-80 years in the United Kingdom-based General Practice Research Database. The first study examined the association between opioid treatment and risk of MI. Current opioid users and those with more than 10 opioid prescriptions had small increased adjusted ORs of around 1.30 compared with nonusers. There was no clear dose-response pattern in the associations between opioid duration of use and risk of MI. Morphine, meperidine, and polytherapy users each had an elevated risk of MI. However, these results could be partially or completely due to bias or confounding given the small increased ORs observed in this study. The second study evaluated the association between opioid treatment and risk of type 2 diabetes mellitus (T2DM). After adjusting for confounders there was no increased risk for T2DM among those exposed to any opioid compared to nonusers (adjusted OR=1.03, 95% CI: 1.00-1.06). Nor was there an effect when we evaluated timing of opioid exposure, duration of use, and individual opioid types. These findings provide reassurance that there is no increased risk of T2DM associated with opioid treatment. The third study examined the association between opioid treatment and risk of fracture. Current short-term opioid users had an increased fracture risk compared to nonusers. However, the risk decreased to the null for current long-term users and for recent or past users. Among current short-term users, there was a 2.75-fold fracture risk for those with one prescription (95% CI: 2.38-3.18), which decreased with increasing number of prescriptions. The findings were consistent for all fracture types including hip, humerus, and wrist sites, and the risk was observed for most opioid analgesics. Since it is likely that use of opioids for chronic non-cancer pain will continue, this dissertation adds valuable safety information on this class of drugs, particularly for longterm use where there is a paucity of data