Inclusion codes for both cohorts.

<div> Background Patients receiving chiropractic spinal manipulation (CSM) for spinal pain are less likely to be prescribed opioids, and some evidence suggests that these patients have a lower risk of any type of adverse drug event. We hypothesize that adults receiving CSM for sciatica will have a reduced risk of opioid-related adverse drug events (ORADEs) over a one-year follow-up compared to matched controls not receiving CSM. Methods We searched a United States (US) claims-based data resource (Diamond Network, TriNetX, Inc.) of more than 216 million patients, yielding data ranging from 2009 to 2024. We included patients aged ≥18 years with sciatica, excluding those post-spine surgery, prior anesthesia, serious pathology, high risk of ORADEs, and an ORADE ≤ 1-year prior. Patients were divided into two cohorts: (1) CSM and (2) usual medical care. We used propensity score matching to control for confounding variables associated with ORADEs. Comparative outcomes were analyzed by calculating risk ratios (RRs) and 95% confidence intervals (CIs) for the incidence of ORADEs and oral opioid prescription between cohorts. Results 372,471 patients per cohort remained after matching. The incidence of ORADEs over 1-year follow-up was less in the CSM cohort compared to the usual medical care cohort (CSM: 0.09%; usual medical care: 0.30%), yielding an RR of 0.29 (95% CI: 0.25–0.32; <i>P</i> < .00001). CSM patients had a lower risk of receiving an oral opioid prescription (RR of 0.68 [95% CI: 0.68–0.69; P < .00001]). Conclusions This study found that adults with sciatica who initially received CSM had a lower risk of an ORADE compared to matched controls not initially receiving CSM, likely explained by a lower probability of opioid prescription. These findings corroborate existing practice guidelines which recommend adding CSM to the management of sciatica when appropriately indicated. </div>