In Medicaid patients, fatal overdose risk rises with opioid dose and sedative-hypnotic use

Compared to low doses, overdose risk is up to five times higher for patients taking moderate to high doses of opioids, and up to 20 times higher in those who use opioids at moderate to high doses together with benzodiazepines, skeletal muscle relaxants, or other sedative-hypnotic drugs, report Renu K. Garg, PhD, and colleagues of University of Washington, Seattle. "Our findings support federal guideline-recommended dosing thresholds in opioid prescribing," the researchers write.

'Dose-Response' Increase in Opioid Overdose Risk

The study included data on more than 150,000 Medicaid patients in Washington State who were prescribed opioids for reasons other than cancer pain -- at least one prescription between 2006 and 2010. The researchers analyzed patterns of opioid use associated with an increased risk of opioid-related death.

The risk of fatal opioid overdose was strongly related to the average daily opioid dose, expressed in "morphine equivalents." Compared to patients in the lowest dose group -- less than 20 milligrams (mg) per day -- risk was doubled for those with moderate opioid doses of 50 to 89 mg per day.

Risk increased further at higher opioid doses, compared to the low-dose group: four times higher at doses between 90 and 199 mg per day, and five times higher at 200 mg per day or higher. Risk was also elevated fivefold for patients using both long-acting and short-acting opioid formulations.

Taking certain sedative-hypnotic medications in addition to opioids further increased the risk of overdose death. Risk was 12 times higher for patients who were taking both benzodiazepines and muscle relaxants. Even among patients in the lowest opioid dose group, risk was five times higher for those taking sedative-hypnotic drugs.

The use of prescription opioid drugs to treat chronic noncancer pain has led to dramatic increases in deaths from opioid overdose. The Centers for Disease Control and Prevention (CDC) considers the Medicaid population to be a high-risk group for fatal opioid overdose. Few previous studies have looked at the relationship between opioid dose and overdose risk among Medicaid patients.

The new results show "a clear dose-response relationship between opioid dose and risk of overdose" among Medicaid patients with noncancer pain, according to Dr. Garg and colleagues. The study also highlights the striking increase in fatal overdose risk among opioid users in patients with concurrent sedative-hypnotic and opioid use. The researchers note that 44 percent of patients in the study received sedative-hypnotics at some time.

"Our findings support the recent CDC opioid prescribing guideline, which underscores the need to practice caution when treating patients with high-risk regimens, including opioid doses of 50 mg/day or higher and concomitant benzodiazepine use," Dr. Garg and coauthors conclude. They add that the increase in fatal overdose isn't limited to long-term users -- risk was significantly higher even for patients with only one to three months of opioid use.