Patient Outcomes After Opioid Dose Reduction Among Patients With Chronic Opioid Therapy

Sara E. Hallvik; Sanae El Ibrahimi; Kirbee Johnston; Jonah Geddes; Gillian Leichtling; P. Todd Korthuis; Daniel M. Hartung


Pain. 2022;163(1):83-90. 

In This Article

Abstract and Introduction


The net effects of prescribing initiatives that encourage dose reductions are uncertain. We examined whether rapid dose reduction after high-dose chronic opioid therapy (COT) associates with suicide, overdose, or other opioid-related adverse events. This retrospective cohort study included Oregon Medicaid recipients with high-dose COT. Claims were linked with prescription data from the prescription drug monitoring program and death data from vital statistics, 2014 to 2017. Participants were placed into 4 mutually exclusive dose trajectory groups after the high-dose COT period, and Cox proportional hazard models were used to examine the effect of dose changes on patient outcomes in the following year. Of the 14,596 high-dose COT patients, 4191 (28.7%) abruptly discontinued opioid prescriptions, 1648 (11.3%) reduced opioid dose before discontinuing, 6480 (44.4%) had a dose reduction but never discontinued, and 2277 (15.6%) had a stable or increasing dose. Discontinuation, whether abrupt (adjusted hazard ratio [aHR] 3.63; 95% confidence interval [CI] 1.42–9.25) or with dose reduction (aHR 4.47, 95% CI 1.68–11.88) significantly increased risk of suicide compared with those with stable or increasing dose. By contrast, discontinuation or dose reduction reduced the risk of overdose compared with those with a stable or increasing dose (aHR 0.36–0.62, 95% CI 0.20–0.94). Patients with an abrupt discontinuation were more likely to overdose on heroin (vs. prescription opioids) than patients in other groups (P < 0.0001). Our study suggests that patients on COT require careful risk assessment and supportive interventions when considering opioid discontinuation or continuation at a high dose.


The opioid crisis continues to be a major public health concern in the United States. Globally, 58 million people used opioids in 2018 accounting for most disability-adjusted life years lost.[41] Compared with other regions in the world, pharmaceutical opioids are drivers of the opioid epidemic in North America.[41] In the same year in the United States, 9.9 million people, representing 3.6% of the population, reported opioid misuse in the past year.[40]

Addressing the opioid epidemic in the United States has focused heavily on reducing opioid prescribing with a notable effect: the national opioid prescribing rate was 51.4 prescriptions per 100 persons in 2018, the lowest in 13 years.[5] Even so, drug overdoses accounted for 67,367 overdose deaths in 2018 with 69.5% of these deaths involving opioids (n = 46,802).[38] Opioid-related adverse events are on the rise among patients without documented opioid prescriptions[25] along with increased use of illicit opioids such as heroin or fentanyl.[8]

After publication of Centers for Disease Control (CDC) Prescribing Opioids for Chronic Pain in 2016,[13] some have raised concern about unintended consequences of aggressive or involuntary tapering of patients on chronic high-dose opioid therapy.[24] Centers for Disease Control Guideline calls for a collaborative approach between clinicians and patients to determine appropriate tapering plans. However, some may integrate elements of the CDC guideline and reduce opioid prescribing in ways that are not sensitive to patient needs or preferences. In fact, some healthcare professionals have identified multilevel barriers to deprescribing (ie, dose reduction and discontinuation),[26] whereas others have suggested opioid "stewardship" toolkits to reduce opioid harms especially in high-prescribing settings (eg, emergency departments).[33]

Few studies have examined unintended effects of abrupt discontinuation on patient outcomes. Patients on chronic opioid therapy in one primary care clinic who discontinued opioid prescriptions had nearly a 3-fold increase in overdose risk.[17] Elevated overdose mortality risk remained high for 3 years after discontinuation of prescription opioids in a Massachusetts cohort.[27] Mark et al. found that many long-term opioid users are discontinued quickly and without prior dose reduction, a pattern that is associated with increased risk of adverse events.[29] This finding focused on the relationship between timing of discontinuation and the risk of an adverse opioid-related event among patients on chronic opioid therapy but did not examine the interaction between dose reduction and discontinuation and did not assess opioid-related deaths or suicide as outcomes.

The aim of this study was to evaluate the association between dose reduction and risk of suicide, opioid overdose, and other opioid-related adverse events among patients with high-dose chronic opioid therapy.