Discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain with and without opioid use disorder in British Columbia, Canada: A retrospective cohort study

Background The overdose crisis in North America has prompted system-level efforts to restrict opioid prescribing for chronic pain. However, little is known about how discontinuing or tapering prescribed opioids for chronic pain shapes overdose risk, including possible differential effects among people with and without concurrent opioid use disorder (OUD). We examined associations between discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain, stratified by diagnosed OUD and prescribed opioid agonist therapy (OAT) status. Methods and findings For this retrospective cohort study, we used a 20% random sample of residents in the provincial health insurance client roster in British Columbia (BC), Canada, contained in the BC Provincial Overdose Cohort. The study sample included persons aged 14 to 74 years on long-term opioid therapy for pain (>= 90 days with >= 90% of days on therapy) between October 2014 and June 2018 (n = 14,037). At baseline, 7,256 (51.7%) persons were female, the median age was 55 years (quartile 1-3: 47-63), 227 (1.6%) persons had been diagnosed with OUD (in the past 3 years) and recently (i.e., in the past 90 days) been prescribed OAT, and 483 (3.4%) had been diagnosed with OUD but not recently prescribed OAT. The median follow-up duration per person was 3.7 years (quartile 1-3: 2.6-4.0). Marginal structural Cox regression with inverse probability of treatment weighting (IPTW) was used to estimate the effect of prescribed opioid treatment for pain status (discontinuation versus tapered therapy versus continued therapy [reference]) on risk of overdose (fatal or nonfatal), stratified by the following groups: people without diagnosed OUD, people with diagnosed OUD receiving OAT, and people with diagnosed OUD not receiving OAT. In marginal structural models with IPTW adjusted for a range of demographic, prescription, comorbidity, and social-structural exposures, discontinuing opioids (i.e., >= 7-day gap[s] in therapy) was associated with increased overdose risk among people without OUD (adjusted hazard ratio [AHR] = 1.44; 95% confidence interval [CI] 1.12, 1.83; p = 0.004), people with OUD not receiving OAT (AHR = 3.18; 95% CI 1.87, 5.40; p < 0.001), and people with OUD receiving OAT (AHR = 2.52; 95% CI 1.68, 3.78; p < 0.001). Opioid tapering (i.e., >= 2 sequential decreases of >= 5% in average daily morphine milligram equivalents) was associated with decreased overdose risk among people with OUD not receiving OAT (AHR = 0.31; 95% CI 0.14, 0.67; p = 0.003). The main study limitations are that the outcome measure did not capture overdose events that did not result in a healthcare encounter or death, medication dispensation may not reflect medication adherence, residual confounding may have influenced findings, and findings may not be generalizable to persons on opioid therapy in other settings. Conclusions Discontinuing prescribed opioids was associated with increased overdose risk, particularly among people with OUD. Prescribed opioid tapering was associated with reduced overdose risk among people with OUD not receiving OAT. These findings highlight the need to avoid abrupt discontinuation of opioids for pain. Enhanced guidance is needed to support prescribers in implementing opioid therapy tapering strategies with consideration of OUD and OAT status. Author summary Why was this study done? In Canada and the United States, a rise in opioid-related morbidity and mortality has prompted system-level efforts to restrict opioid prescribing for chronic pain. Guidelines implemented in Canada and the United States have recommended tapering prescribed opioids for pain to the lowest effective dose, potentially discontinuing therapy, among people receiving opioid therapy for chronic pain when risks outweigh benefits. Although there is emerging evidence to suggest that deprescribing opioid therapy for chronic pain may increase risk of opioid-related harms, most existing studies have focused on non-representative subpopulations. To our knowledge, no studies to date have examined whether the effects of discontinuing and tapering opioid therapy for pain on overdose risk might differ among people with and without concurrent opioid use disorder. What did the researchers do and find? Drawing on administrative data linked at the individual level for a random sample of residents registered in the provincial health insurance client roster in British Columbia, Canada, we identified 14,037 persons prescribed long-term opioid therapy for pain between October 2014 and June 2018. We examined associations between discontinuation and tapering of prescribed opioid therapy for pain (versus continued treatment) and risk of overdose, stratified by whether patients had been diagnosed with opioid use disorder and recently prescribed opioid agonist therapy. We found that discontinuing opioid therapy for pain was associated with increased overdose risk among people without opioid use disorder (adjusted hazard ratio [AHR] = 1.44; 95% confidence interval [CI] 1.12, 1.83; p = 0.004). However, stronger associations were observed among people with opioid use disorder, including those not receiving opioid agonist therapy (AHR = 3.18; 95% CI 1.87, 5.40; p < 0.001) and those receiving opioid agonist therapy (AHR = 2.52; 95% CI 1.68, 3.78; p < 0.001). Tapering opioid therapy for pain was associated with decreased overdose risk among people with opioid use disorder not receiving opioid agonist therapy (AHR = 0.31; 95% CI 0.14, 0.67; p = 0.003). What do these findings mean? Abrupt discontinuation of prescribed opioid treatment for pain is contraindicated given its association with increased risk of overdose. Enhanced guidance is needed to support healthcare providers in implementing safe and effective strategies for tapering opioid treatment for pain that are tailored to the unique needs of individual patients, with particular consideration of opioid use disorder and prescribed opioid agonist therapy status.