Toronto, Canada—The anticonvulsant gabapentin is often prescribed off-label to patients with chronic pain. A new study warns, however, that its use in conjunction with opioid painkillers can increase the risk of death.

The report in PLOS Medicine points out that both drugs can suppress breathing and that gabapentin might also increase the absorption of opioids.

To come to their conclusion, University of Toronto researchers conducted a case-control study, focusing on 1,256 opioid users who died of an opioid-related cause and comparing them with 4,619 matched controls who also used opioids but did not die of an opioid-related cause in that window of time.

In the 120 days prior to the study period, 12.3% of the group dying of an opioid-related cause and 6.8% of the controls also were prescribed gabapentin.

Background information in the article notes that prescription opioid use alone increases death risk, with one of every 550 chronic opioid users dying within approximately 2.5 years of their first opioid prescription. While gabapentin is considered to be safe, drug-induced respiratory depression has raised concerns about potential dangers, the report states.

With a paucity of research on the topic, the study authors sought to investigate whether coprescription of opioids and gabapentin is associated with an increased risk of accidental opioid-related mortality.

Results indicate that the combination is potentially deadly; concurrent use of gabapentin and opioids was associated with a 49% higher risk of dying from an opioid overdose compared with opioid use alone, for an adjusted odds ratio of 1.49.

A dose-response analysis found that moderate-dose gabapentin, with an odds ratio (OR) of 2.05, and high-dose gabapentin—defined as 1,800 mg daily or more, for an OR of 2.20—were especially dangerous.

On the other hand, in a sensitivity analysis, no significant association was detected between coprescription of opioids and nonsteroidal anti-inflammatory drugs and opioid-related deaths, for an OR of 1.11.

Applicability of the results could be limited because the population studied consisted of people eligible for public drug coverage in Ontario, which disproportionately represented low-income neighborhoods, the study authors point out.

“Clinicians should consider carefully whether to continue prescribing this combination of products, and when deemed necessary, should closely monitor their patients and adjust opioid dose accordingly,” the study authors conclude.

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