Associations Between Initial Opioid Exposure and the Likelihood for Long-term Use

George Cullina, Pharm.D., Cashwise Clinic Pharmacy / ACMC

According to the Centers for Disease Control and Prevention, more than 700,000 people have died from a drug overdose between 1999 and 2017. Nearly 68% of the 70,200 drug overdose deaths in 2017 involved an opioid. That same year, the opioid epidemic was declared a public health emergency by the U.S. Department of Health and Human Services. Since then, there have been many initiatives to reduce prescribing of opioids and to treat those affected by addiction. Another important area of study is identifying factors that may influence or lead to chronic opioid use. A study in JAPhA examined the association between initial opioid exposure and the likelihood for long-term opioid use.

The study compared two cohorts within the Veteran’s Affairs Health System; 317,367 patients from 2016 compared with 376,140 patients in 2011. The study compared multiple independent variables to identify which, if any, factors of initial opioid exposure are associated with long-term opioid use. These factors included number of opioid prescriptions filled within 30 days, the total morphine milligram equivalents (MME) dispensed, the day supply, and mean daily dose of MME. The number of opioid prescriptions filled within 30 days, the total MME dispensed, and the day supply were all independent risk factors with a positive linear relationship that demonstrated an association with the likelihood of long-term opioid use. The mean daily MME was also associated with an increased likelihood of long-term opioid use, but only when greater than 45 MME per day. Among initial opioid exposure metrics, the findings clarify that cumulative days of exposure, whether delivered in a single prescription or as multiple short-term prescriptions, is the strongest determinant of subsequent long-term use.

This information supports the recent restriction put on new opioid prescriptions by Minnesota Medicaid health insurance as of October 2018. The new restriction limits the day supply of opioid-naive patients to seven days. This limitation should help reduce the risk for future long-term opioid use as a days supply of less than or equal to seven days had the lowest associated risk of long-term opioid use within the study.  This information could also be used to proactively identify patients that are at risk for long-term opioid use. Identification of high-risk patient while they are still in the acute or subacute treatment window and subsequent referral to pain specialists may prevent long-term opioid use before it happens.


  1. Opioid overdose. Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 19 Dec. 2018, Published December 19, 2018. Accessed February 15, 2019.

  2. Hadlandsmyth K, Lund B, Mosher H. Associations between initial opioid exposure and the likelihood for long-term use. JAPhA. 2019;59(1):17–22. doi:10.1016/j.japh.2018.09.005.