Nonfatal Opioid Overdose Greatly Raises Risk of Short-Term Death

Mark Olfson, MD, MPH

Adult survivors of opioid overdoses are at greater risk of death in the year following the incident, commonly from associated diseases, infectious disease, cancer, or suicide. However, marketed therapies to treat opioid use disorder have been proven to decrease the risk of death in the same survivors.

Led by author Mark Olfson, MD, MPH, researchers from Columbia University conducted an observational study of 76,325 Medicaid beneficiaries who experienced nonfatal opioid overdoses between 2001-2007. What they found was a significant crude death rate in the immediate year of recovery, indicating an unmet need for more comprehensive care in the wake of the opioid crisis.

Researchers analyzed 66,736 person-years of follow-up period among the 76,000-plus patients. They determined crude mortality rates per 100,000 person-years in the first year following a nonfatal opioid overdose, and estimated standardized mortality rates (SMR) for both all-cause and selected cause-specific mortality standardized to the general population with regards to age, sex, and race/ethnicity.

The cohort was restricted to adults 18-64 years old, who were at the time of care eligible for Medicaid services. Nonfatal opioid overdoses were identified as both pharmaceutical drug and heroin-related overdoses coded as having been done unintentionally or without known intent. None of the observed patients provided more than 1 observation to the cohort.

Among the patients, 5194 had died within 1 year of their observed nonfatal overdose. Researchers determined an all-cause mortality rate of 778.3 per 10,000 person-years for adults after opioid overdose — a rate more than 24 times greater than that provided with age, sex, and race/ethnicity-matched community controls (SMR 24.2; 95% CI; 23.6 — 24.9).

Young adults aged 18-34 years reported even greater all-cause SMR (39.1), and women (27.3) reported greater rates than men (21.7).

Causes of death were predictably centered around substance-associated disease, accounting for 1363 (26.2%) of all deaths. Circulatory system diseases (n = 689; 13.2%) and cancer (n= 536; 10.3%) were also prominent drivers of death in patients.

The SMR for drug-use associated deaths exceeded all at 132.1 (95% CI; 39.5 — 53.0). Other diseases with elevated SMRs included HIV (45.9; 95% CI; 39.5 – 53.0), chronic respiratory disease (41.1; 95% CI; 36.0 – 46.8), viral hepatitis (30.6; 95% CI; 22.9 – 40.2), and suicide (25.9; 95% CI; 22.6 – 29.6).

Researchers noted the analysis comes in light of recent reports that opioid-related inpatient admissions and emergency department visits are rising in the US, emphasizing the urgency for measures to treat overdose, addiction, and now any last symptoms of a nonfatal overdose.

“The magnitude of this loss of life and variety of medical diseases that contribute to these excess deaths underscores the medical frailty of these patients and emphasizes the importance of coordinating addiction treatment, general medical services, and mental health care after opioid overdose,” researchers wrote.

The news is also coupled with recently-reported research from the National Institutes of Health (NIH) which found that treating nonfatal opioid overdose with methadone or buprenorphine could significantly reduce a patient’s risk in drug-related mortality.

Using data from 17,568 adult opioid overdose survivors in Massachusetts between 2012-2014, NIH researchers found that overdose deaths decreased by 59% and 38% in those to receive methadone or buprenorphine, respectively, over the next 12 months.

The medications, popularized as assisted therapy for opioid addiction recovery, are still underutilized. In the first year following an overdose, less than one-third of patients were provided therapy for opioid use disorder (OUD), according to the study. Buprenorphine was administered to 17% of all patients, and methadone to just 11%.

Shockingly, more than one-third (34%) of overdose survivors were actually prescribed at least 1 opioid painkiller over the next 12 months. Another 26% were prescribed benzodiazepines.

Lead study investigator Marc Larochelle, MD, of Boston Medical Center’s Grayken Center for Addiction and Boston University School of Medicine, echoed the sentiments of the Columbia University research when stating that the time following a nonfatal opioid overdose is a “missed opportunity to engage individuals at high risk of death.”

“We need to better understand barriers to treatment access and implement policy and practice reforms to improve both engagement and retention in effective treatment,” Larochelle said.

Researchers were unable to meet conclusive analysis of naltrexone, the third therapy approved by the US Food and Drug Administration to treat OUD, due to a smaller sample size.

The Columbia University study, "Causes of Death After Nonfatal Opioid Overdose," was published online in JAMA Psychiatry Wednesday.

The NIH study, "Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study," was published online in Annals of Internal Medicine Tuesday.