In a study that followed thousands of veterans over a decade, initiating non-medical use of opioid painkillers was associated with a more than 5-fold risk of also beginning to use heroin.

PROVIDENCE, R.I. [Brown University] — A study of nearly 3,400 military veterans over 10 years found that when participants began to misuse opioid painkillers, they had a very high likelihood of also beginning to use heroin, researchers reported in the journal Addiction. As a result, the authors recommend that health care providers who serve veterans should watch closely for signs of non-medical use of opioid painkillers.

“This study quantifies the issue of starting painkiller misuse and heroin use in a specific, high-risk population — veterans around the U.S.,” said corresponding author Brandon Marshall, Manning Assistant Professor in the Brown University School of Public Health. “Of the 500 participants who initiated heroin, 77 percent reported prior or concurrent non-medical prescription painkiller use.”

Even after statistically accounting for many other risks — such as race, income, use of other drugs, and PTSD or depression — researchers found that veterans who began misusing painkillers were 5.4 times more likely than those who did not to begin using heroin.

Veterans at risk

Geetanjoli Banerjee, a graduate student in Marshall’s research group at Brown, led the analysis. She and Marshall worked closely with colleagues at Yale University to study a subset of participants in the Veterans Aging Cohort Study (VACS). In total, VACS has followed more than 7,000 HIV-infected and similar uninfected veterans engaged in care at nine Veterans Affairs facilities around the country. The overall study tracks how alcohol use, as well as concurrent medical and psychiatric disease, may affect clinical outcomes in HIV infection. As such, the study is a broad subset, but not a perfectly representative sample of all veterans.

For the new analysis in Addiction, Banerjee and Marshall focused on 3,396 VACS participants who at the study’s beginning in 2002 said they had never used opioids for non-medical reasons or heroin. About 2,800 VACS participants had already misused painkillers or heroin when the study began, so they were not included in the analysis.

“Our findings demonstrate a pattern of transitioning from non-medical use of prescription opioids to heroin use that has only been demonstrated in select populations,” said study co-author David Fiellin, a Yale public health and medical professor and director of the VACS study intervention group. “Our findings are unique in that our sample of individuals consisted of patients who were receiving routine medical care for common medical conditions.”

Biggest among many risk factors

Though none of the veterans in the new analysis reported misusing opioids previously, a total of 1,416 had begun non-medical use of opioid painkillers by 2012. Of the 500 veterans in the study who began using heroin, 386 had also begun using prescription painkillers non-medically.

By far the best predictor in the data of who ended up using heroin was non-medical use of opioid painkillers. Other sociodemographic risk factors, controlling for all others, were being male (2.6-fold risk) or being black (2-fold risk). Abusing stimulant drugs (versus not doing so) was associated with a 2.1-fold risk of using heroin.

Receiving a short-term prescription for an opioid painkiller was associated with a less than 1.7-fold risk of starting heroin. A longer-term prescription was not significant as a risk factor at all.

Veterans clearly experience what Marshall called a “constellation of risks” for substance use. But among doctors who treat veterans, whether they are in the Veterans Affairs system or not, the study findings suggest they should screen for painkiller misuse, Marshall said. As dangerous as that addiction can be, progression to heroin carries substantial additional dangers including contamination with other opioids like fentanyl, and injection-associated infections such as hepatitis C or HIV.

“This paper shows that, as a general clinical practice, particularly for this population which does experience a lot of chronic pain and other risks for substance use including PTSD, screening for non-medical painkiller use, whether you are prescribing an opioid or not, may be effective to prevent even more harmful transitions to heroin or other drugs,” Marshall said.

The data leaves questions unanswered, such as the source of the opioids that were used non-medically, why non-medical opioid painkiller use progresses to heroin use, and exactly what practices would prevent that. Banerjee and Marshall are therefore conducting several follow-up analyses. In one they are focusing on whether there is a significant progression from a short-term painkiller prescription to misuse to heroin. In another they are looking at whether geography makes a difference. Heroin prices vary widely around the country, meaning that it may not be much of a low-cost alternative to prescription painkillers in some areas.

The National Institutes of Health and the U.S. Department of Veterans Affairs supported the study.

In addition to Marshall, Banerjee and Fiellin, the paper’s other authors are Jennifer Edelman, Declan Barry, William Becker, Magdalena Cerda, Stephen Crystal, Julie Gaither, Adam Gordon, Kirsha Gordon, Robert Kerns and Silvia Martins.