Before the First Prescription: Who Is Most at Risk for Long-Term Opioid Use After Surgery

For many people in the United States, their first exposure to opioid pain medication happens after a routine surgical procedure. Most patients taper off these medications as healing progresses. However, a meaningful subset of individuals who have never previously used opioids—often described as “opioid-naïve”—continue taking them well beyond the expected recovery window. This pattern, known as new persistent opioid use (NPOU), can mark the beginning of long-term dependence and serious health consequences.

A newly published systematic review and meta-analysis led by researchers at Penn Nursing, appearing in Pain Medicine, sheds important light on which patients are most vulnerable to this transition. By analyzing data from 27 high-quality studies, the research team identified a small but powerful set of patient-level risk factors that consistently predict who is most likely to develop persistent opioid use following surgery.

The analysis found four factors that significantly raise the likelihood of long-term opioid use after an operation: enrollment in Medicaid, use of benzodiazepines before surgery, a history of mood disorders, and pre-existing anxiety.

“Knowing who is at higher risk before surgery even begins is essential to addressing the broader opioid crisis,” said lead author Yoonjae Lee, DNP, APRN, a doctoral researcher involved in the study. “These findings give clinicians practical guidance to identify vulnerable patients early and tailor pain-management plans that reduce harm while still addressing pain effectively.”

Breaking down the risk factors

Using pooled odds ratios—a statistical measure that reflects how strongly each factor is associated with persistent opioid use—the researchers quantified the impact of each risk factor:

• Medicaid enrollment and preoperative benzodiazepine use: These emerged as the strongest predictors. Patients in either category had a 77% higher likelihood of developing NPOU compared to those without these characteristics.

• Mood disorders: Individuals with a history of depression or other mood-related conditions experienced a 24% increase in risk.

• Anxiety disorders: Patients with pre-existing anxiety faced a 17% higher chance of continuing opioid use long after surgery.

Rethinking preoperative screening

NPOU is typically defined as ongoing opioid use more than three months after surgery. This pattern has been linked to higher rates of illness, increased risk of death, and long-term complications that extend well beyond pain control.

One of the study’s most important takeaways is that being “opioid-naïve” does not automatically mean a patient is low risk. Social factors—such as insurance coverage—and mental health conditions can be just as influential as the surgical procedure itself in determining outcomes. The researchers argue that preoperative evaluations should move beyond a narrow focus on the surgery and instead incorporate broader screening for psychological and social risk factors.

By applying these evidence-based insights in clinical settings, healthcare teams can intervene earlier, offer alternative pain-management strategies, and monitor high-risk patients more closely. Doing so may help prevent unintended long-term opioid use and improve recovery and quality of life for patients across the country.

Source: Medical Xpress