Richmond, Va. – April 13, 2017 – Individuals suffering from a substance use disorder (SUD) or depression are among those at highest risk for a serious prescription opioid overdose, according to a study published in Pain Medicine.

The retrospective, case-control study analyzed and compared patients with an opioid prescription from two health care claims databases: the U.S. Veterans Health Administration (VHA) from 2010-12 (1.9 million patients) and a U.S. commercial health plan database (IMS PharMetrics Plus) from 2009-13 (18.3 million patients). Risk factors for overdose in the 7,234 overdose cases in the commercially insured population (CIP) were analyzed and compared with the risk factor profile for the 817 VHA overdose cases. This is the most comprehensive characterization and comparison published to date of U.S. medical users of prescription opioids and overdose cases.

The strongest risk factors for prescription opioid overdose in the CIP were diagnosed depression and SUD of any type — not just opioid dependence, abuse or addiction. Other strongly associated factors included other mental health disorders; impaired liver, kidney, vascular or lung function; and non-cancer pancreatic disease. A high total daily opioid dose, certain opioids and extended-release or long-acting opioids also were strong predictors of overdose. Taking certain other medications that affect the mind or behavior, such as benzodiazepines or antidepressants, increased an opioid user’s risk of overdose. The risk factor profiles largely were similar between the two populations despite substantial population differences in demographics, pre-existing health conditions, current medications, recent emergency department visits and hospitalizations, as well as differences between the public and private health care systems including medication prescribing practices and drug formularies.

There was considerably greater prescribing prevalence of higher total daily opioid doses, all opioids except morphine and methadone, and most non-opioid medications, including psychoactive drugs, in the CIP overall than in the VHA population. However, extended-release or long-acting opioids were prescribed only about half as frequently among overdose cases in the CIP as in VHA.

Prescription opioid sales have quadrupled in the United States between 1999 and 2010 [1], and opioid prescription use increased by 31 percent between 2000 and 2005 among commercially insured patients [2]. Between 2004 and 2012, opioid use increased 77 percent among VHA patients [3]. Pain management is complex and multidimensional, and the risk of an opioid overdose is dependent on multiple factors.

“Any treatment plan involving opioids requires an individualized approach due to the potential for a serious overdose in all patients, regardless of age or indication,” said Barbara Zedler, M.D., senior author and chief medical officer of Venebio, a life sciences consultancy. “Safe and appropriate opioid prescribing requires a personalized approach that accounts for a patient’s demographic and psychosocial characteristics, active clinical conditions, other medications and substances used, and opioid-specific characteristics.”

Venebio is the developer of the only validated opioid risk index and clinical decision support tool available — Venebio Opioid Advisor (VOA) — that calculates a patient’s likelihood of a life-threatening overdose from a prescription opioid, determines their personalized risk factor profile and gives individualized guidance regarding interventions that health care professionals can consider to reduce the patient’s risk of overdose. Ongoing development of VOA is supported by a $1.5-million grant from the National Institute on Drug Abuse of the National Institutes of Health.

The study, “Risk Factors for Serious Prescription Opioid-induced Respiratory Depression or Overdose: Comparison of Commercially Insured and Veterans Health Affairs Populations” was co-funded by Venebio and Kaléo, Inc., a privately held pharmaceutical company. The full study can be read at: and additional information is available at

[1] Paulozzi L, Jones C, Mack KA, Rudd R. Vital signs: Overdoses of prescription opioid pain relievers – United States, 1999-2008. MMWR Morb Mortal Wkly Rep 2011;60(43):1487-92.

[2] Sullivan MD, Edlund MJ, Fan MY, et al. Trends in use of opioids for non-cancer pain conditions 2000-2005 in commercial and Medicaid insurance plans: The TROUP study. Pain 2008; 138(2):440-9.

[3] Mosher HJ, Krebs EE, Carrel M, et al. Trends in prevalent and incident opioid receipt: An observational study in Veterans Health Administration 2004-2012. J Gen Intern Med 2015;30(5):597-604.