Do Formulation and Dose of Long-Term Opioid Therapy Contribute to Risk of Adverse Events among Older Adults?

Background Chronic non-cancer pain (CNCP) is highly prevalent in older adults and long-term opioid therapy (LTOT) has been used to manage chronic pain. However, the safety of LTOT among older adults with CNCP is not well-established and there is a need to identify therapy-related risk factors of opioid-related adverse events among older adults. Objective To evaluate the relationship between opioid dose and formulation and the risk of opioid-related adverse events among Medicare-eligible older adults on LTOT. Design Nested case-control study. Participants Older Medicare beneficiaries (N=35,189) who received > 3 opioid prescriptions with a total days-supply of >45 days within a 90-day period for CNCP between 2012 and 2016. Main Measures This study utilized Medicare 5% medical and prescription claims data. Outcome measures included opioid-induced respiratory depression (OIRD), opioid overdose, all-cause mortality, and a composite outcome, defined as the first occurrence of any of the previous three events. Key independent variables were opioid formulation and opioid dose (measured in morphine milligram equivalents (MME)) prescribed during LTOT. Key Results Seventy-four OIRD, 133 overdose, 982 all-cause mortality, and 1122 composite outcome events were observed during follow-up. In unadjusted analyses, the use of combination opioids (OR: 4.52 [95%CI: 1.51-13.47]) was significantly associated with OIRD compared to short-acting (SA) opioids. In adjusted analyses, opioid-related adverse events were significantly associated with the use of LA (overdose OR: 13.00 [95%CI: 1.30-130.16] and combination opioids (overdose OR: 6.27 [95%CI: 1.91-20.55]; mortality OR: 2.75 [95%CI: 1.87-4.04]; composite OR: 2.82 [95%CI: 2.01-3.96]) when compared to SA opioids. When compared to an average dose of less than 20 MME, outcomes were significantly associated with doses of 20-50 MME (mortality OR: 1.61 [95%CI: 1.24-2.10]; composite OR: 1.59 [95%CI: 1.26-2.01]) and >50 MME (mortality OR: 1.99 [95%CI: 1.28-3.10]; composite OR: 2.09 [95%CI: 1.43-3.04]). Conclusions Older adults receiving medically prescribed opioids at higher doses and those using LA and combination of LA and SA opioids are at increased risks for opioid-related adverse events, highlighting the need for close patient supervision.