Trajectories of prescription opioid dose and risk of opioid-related adverse events among older Medicare beneficiaries in the United States: A nested case–control study

Abstract

Background Despite the rising number of older adults with medical encounters for opioid misuse, dependence, and poisoning, little is known about patterns of prescription opioid dose and their association with risk for opioid-related adverse events (ORAEs) in older patients. The study aims to compare trajectories of prescribed opioid doses in 6 months preceding an incident ORAE for cases and a matched control group of older patients with chronic noncancer pain (CNCP). Methods and findings We conducted a nested case–control study within a cohort of older (≥65 years) patients diagnosed with CNCP who were new users of prescription opioids, assembled using a 5% national random sample of Medicare beneficiaries from 2011 to 2018. From the cohort with a mean follow-up of 2.3 years, we identified 3,103 incident ORAE cases with ≥1 opioid prescription in 6 months preceding the event, and 3,103 controls matched on sex, age, and time since opioid initiation. Key exposure was trajectories of prescribed opioid morphine milligram equivalent (MME) daily dosage over 6 months before the incident ORAE or matched controls. Among the cases and controls, 2,192 (70.6%) were women, and the mean (SD) age was 77.1 (7.1) years. Four prescribed opioid trajectories before the incident ORAE diagnosis or matched date emerged: gradual dose discontinuation (from ≤3 to 0 daily MME, 1,456 [23.5%]), gradual dose increase (from 0 to >3 daily MME, 1,878 [30.3%]), consistent low dose (between 3 and 5 daily MME, 1,510 [24.3%]), and consistent moderate dose (>20 daily MME, 1,362 [22.0%]). Few older patients (<5%) were prescribed a mean daily dose of ≥90 daily MME during 6 months before diagnosis or matched date. Patients with gradual dose discontinuation versus those with a consistent low dose, moderate dose, and increase dose were more likely to be younger (65 to 74 years), Midwest US residents, and receiving no low-income subsidy. Compared to patients with gradual dose discontinuation, those with gradual dose increase (adjusted odds ratio [aOR] = 3.4; 95% confidence interval (CI) 2.8 to 4.0; P < 0.001), consistent low dose (aOR = 3.8; 95% CI 3.2 to 4.6; P < 0.001), and consistent moderate dose (aOR = 8.5; 95% CI 6.8 to 10.7; P < 0.001) had a higher risk of ORAE, after adjustment for covariates. Our main findings remained robust in the sensitivity analysis using a cohort study with inverse probability of treatment weighting analyses. Major limitations include the limited generalizability of the study findings and lack of information on illicit opioid use, which prevents understanding the clinical dose threshold level that increases the risk of ORAE in older adults. Conclusions In this sample of older patients who are Medicare beneficiaries, 4 prescription opioid dose trajectories were identified, with most prescribed doses below 90 daily MME within 6 months before ORAE or matched date. An increased risk for ORAE was observed among older patients with a gradual increase in dose or among those with a consistent low-to-moderate dose of prescribed opioids when compared to patients with opioid dose discontinuation. Whether older patients are susceptible to low opioid doses warrants further investigations.

Five-Year Trajectories of Prescription Opioid Use

“…Although the outcomes associated with trajectory group membership were not examined, there is evidence that trajectories with higher opioid use may be associated with an increased risk of harms. A study of people 65 years or older with CNCP and new opioid use found that individuals with increasing or consistent opioid dose trajectories had a higher risk of opioid-related adverse events than those with decreasing opioid dose trajectories . Similarly, studies examining opioid use among US veterans identified higher risk of opioid-related adverse events, hospitalization, and all-cause mortality among high use and increasing use groups .…”

Long-term health-related quality of life and independence among older survivors of serious injury

“…Prior work has demonstrated a high prevalence of persistent pain after serious injury among adults of all ages, 37 however little is known regarding the incidence of chronic pain among older adults after serious injury. Given rising rates of opioid misuse, dependence, and overdose among older adults, 38,39 future studies might also examine persistent pain postinjury as a risk factor for opioid-related adverse events.…”

A Group-Based Intervention to Reduce Opioid Use for Chronic Pain

“…Slower reductions, with patient collaboration and shared decision-making, are crucial for adherence and sustained reductions. 2 Third, we are concerned that 25% of patients dropped out of the study, and 87% of recruited individuals did not achieve the 100% taper goal. Failure to reduce opioids is not without consequences.…”

“…Fourth, we believe that this study overlooked the complexity of opioid dependence, 4 the challenges in tapering opioids, and the potential risks of mental health deterioration associated with opioid cessation. 2 Additionally, the necessity of tapering opioids in patients who are functioning well with lowdose opioids deserved further discussion.…”

“…Medicare data showed that people prescribed 35 mg of morphine had more opioid-related adverse effects than those taking 20 mg daily and those who were in the process of reducing their opioid dose. 2 There are potential health benefits from tapering from any baseline opioid use level. Recent evidence showed long-term harms from low-dose opioids used for acute spinal pain.…”