Gomes T, et al. - Authors investigated if co-prescription of opioids and gabapentin exhibited a tie-up with an increased risk of accidental opioid-related mortality. A link was illustrated between concomitant treatment with gabapentin with a significant rise in the risk of opioid-related death, among patients receiving prescription opioids. Clinicians were recommended to carefully investigate whether to continue prescribing this combination of products and when the combination was deemed necessary. Close monitoring of the patients, along with adjustment of opioid dose were also suggested. In order to determine the existence of a similar interaction between pregabalin and opioids, additional analyses were warranted.

Methods

• A population-based nested case-control study was carried out among opioid users, residing in Ontario, Canada.
• It was conducted between August 1, 1997, and December 31, 2013, using administrative databases.
• Herein, the cases, defined as opioid users who died of an opioid-related cause, were matched with up to 4 controls who also used opioids on age, sex, year of index date, history of chronic kidney disease, and a disease risk index.
• A total of 1,256 cases and 4,619 controls were enrolled.
• The primary exposure consisted of concomitant gabapentin use in the 120 days preceding the index date.
• A secondary analysis characterized gabapentin dose as low (<900 mg daily), moderate (900 to 1,799 mg daily), or high (≥1,800 mg daily).
• A sensitivity analysis analyzed the impact of concomitant nonsteroidal anti-inflammatory drug (NSAID) use in the preceding 120 days.

Results

• Gabapentin was prescribed in 12.3% of cases (155 of 1,256) and 6.8% of controls (313 of 4,619) in the prior 120 days.
• After multivariable adjustment, co-prescription of opioids and gabapentin exhibited a link with a considerably raised odds of opioid-related death (odds ratio [OR] 1.99, 95% CI 1.61 to 2.47, p < 0.001; adjusted OR [aOR] 1.49, 95% CI 1.18 to 1.88, p < 0.001) than with the opioid prescription alone.
• In the dose-response analysis, moderate-dose (OR 2.05, 95% CI 1.46 to 2.87, p < 0.001; aOR 1.56, 95% CI 1.06 to 2.28, p=0.024) and high-dose (OR 2.20, 95% CI 1.58 to 3.08, p < 0.001; aOR 1.58, 95% CI 1.09 to 2.27, p=0.015) gabapentin use was related to an approximately 60% increase in the odds of opioid-related death relative to no concomitant gabapentin use.
• No prominent link was discovered between co-prescription of opioids and NSAIDs and opioid-related death (OR 1.11, 95% CI 0.98 to 1.27, p=0.113; aOR 1.14, 95% CI 0.98 to 1.32, p=0.083).
• In an examination of the patients at risk of combined opioid and gabapentin use, 46.0% (45,173 of 98,288) of gabapentin users in calendar year 2013 received at least 1 concomitant prescription for an opioid.
• The trial exhibited limitation to individuals eligible for public drug coverage in Ontario.
• Only prescriptions reimbursed by the government and dispensed from retail pharmacies were identified, and information on indication for gabapentin use remained unavailable.
• Confounding due to unmeasured variables served as a potential source of bias.