Predictors and Clinical Outcomes of Long-Term Opioid Therapy in Older Adults: A Systematic Review

Older adults have a higher prevalence of pain and are more likely to receive long-term opioid therapy (LTOT) compared to other age groups. They are also at elevated risk of opioid-related adverse events due to physiological changes and polypharmacy. This systematic review aimed to identify predictors and clinical outcomes associated with LTOT in older adults.

We searched PubMed, Embase, and Cochrane Library to identify randomized clinical trials (RCT) and observational studies published from inception until July 31, 2025. We included studies that examined opioid use for ≥ 90 days and included participants aged ≥ 60 years. Data were synthesized using harvest plots and narrative synthesis. The Newcastle-Ottawa Scale was used for risk of bias assessment.

Forty-one observational studies were included; no RCTs met the inclusion criteria. Patient-related factors associated with LTOT across most studies were low income/wealth (n = 6/6 studies), depressive disorders (n = 6/9 studies), and dual insurance eligibility/enrollment (n = 4/6 studies). Prescription/dispensation-related factors associated with LTOT across most studies were opioid use before surgery/trauma (n = 6/6 studies), prior/concurrent use of benzodiazepines (n = 6/6 studies), anxiolytics/sedatives/hypnotics (n = 3/4 studies), anticonvulsants (n = 3/4 studies), opioid use after surgery/trauma (n = 3/3 studies), long-acting opioids (n = 3/3 studies), and longer duration of initial opioid (n = 2/2 studies). Regarding outcomes of LTOT, most studies reported positive associations between LTOT and hospital readmission/emergency department visit (n = 3/4 studies), revision surgery (n = 2/2 studies), health care costs (n = 2/2 studies), opioid overdose (n = 1/1 study), and falls (n = 1/1 study). Evidence on the association of LTOT with mortality and fractures was inconclusive.

This systematic review identified several predictors and adverse outcomes associated with LTOT in older adults. However, no evidence exists regarding the effectiveness of LTOT for pain management in this population. Prospective studies with long-term follow-up are needed to address this gap and inform benefit-harm assessment of LTOT in clinical practice.