Overdose risk higher with concomitant use of Z-Drugs, prescription opioids

Treatment with Z-drugs (zolpidem, zopiclone, zaleplon) appears to result in a marked increase in the risk of overdose among patients receiving prescription opioids, reveals a recent study. The potential implications are noteworthy due to the large number of opioid-treated patients using Z-drugs.

The investigators identified all individuals aged 15–85 years who had received prescription opioids, regardless of underlying indication and without evidence of cancer, in the IBM MarketScan database (2004–2017). Patients with concomitant exposure to Z-drugs were matched 1:1 to those on prescription opioids alone based on opioid prescribed, morphine equivalents, number of days’ supple, and hospitalization within the past 30 days.

Any hospitalization or emergency department visit due to an overdose within 30 days, using an intention-to-treat approach, was the primary outcome. Confounding factors were controlled using fine stratification on the propensity score.

Overall, 510,529 exposed patients and an equal number of matched reference patients were analysed. Overdose events were significantly higher among exposed patients (217, 52.5 events per 10,000 person-years) than reference participants (57, 14.4 events per 10,000 person-years), which corresponded to an unadjusted hazard ratio (HR) of 3.67 (95 percent confidence interval [CI], 2.75–4.90). The unadjusted HR using fine stratification on the propensity score (c-statistic, 0.66) was 2.29 (95 percent CI, 1.79–2.91).

Sensitivity analyses confirmed these results.

“The Z-drugs are widely used to treat insomnia in patients receiving prescription opioids,” the investigators noted.