Prescription Sequence Symmetry Analysis for Detection of Chronic Opioid Use Adverse Event Signals Using Administrative Claims Data

Introduction: Opioids are commonly used to manage chronic pain in older adults, despite their well-documented adverse events (AEs) and the potential for additional less well-known risks. Post-marketing surveillance methods applied in real-world settings are essential to monitor AEs. Prescription Sequence Symmetry Analysis (PSSA) is a method that compares medication initiation patterns within individuals and can detect signals of prescribing cascades and drug AEs. This study applied PSSA to Medicare claims data to explore potential AEs following the initiation of long-term opioid therapy (LOT). Methods: We used Texas-Medicare data to identify adults who initiated LOT (≥ 90 consecutive days) in 2016–2019. Prescription sequence symmetry analysis (PSSA) was performed to explore associations between opioids and related adverse events treated by marker drugs. The observation period for sequences of incident marker drug prescriptions was limited to 12 months before and after opioid initiation. Marker drugs were categorized based on the Anatomical Therapeutic Chemical (ATC) Classification System. Adjusted sequence symmetry ratios (aSSR) and 95% confidence intervals were calculated to account for prescribing trend changes. Results: Among 11,233 incident opioid users, we identified incident marker drugs belonging to 145 distinct ATC classes, 36 of which had statistically significant aSSRs. We found signals of increased post-opioid prescriptions related to known opioid AEs (e.g., propulsives, antiemetics, laxatives, naltrexone) and less well-documented associations (antimicrobials, hormones, antiarrhythmics, and antipsychotics). Conclusions: PSSA applied to administrative claims data effectively identified both expected and potentially underrecognized adverse effects of long-term opioid use. This approach can enhance post-marketing surveillance by uncovering real-world prescribing cascades in older adults.