Concurrent use of opioids and benzodiazepines/Z-drugs in Alberta, Canada and the risk of hospitalisation and death: a case cross-over study.

Objectives: Coprescribing of benzodiazepines/Z-drugs (BZDs) and opioids is a drug-use pattern of considerable concern due to risk of adverse events. The objective of this study is to estimate the effect of concurrent use of BZDs on the risk of hospitalisations/emergency department (ED) visits and deaths among opioid users.

Design, Setting And Participants: We conducted a population-based case cross-over study during 2016-2018 involving Albertans 18 years of age and over who received opioids. From this group, we identified 1 056 773 people who were hospitalised or visited the ED, and 31 998 who died.

Intervention: Concurrent use of opioids and BZDs.

Outcomes: We estimated the risk of incident all-cause hospitalisation/ED visits and all-cause mortality associated with concurrent BZD use by applying a matched-pair analyses comparing concurrent use to opioid only use.

Results: Concurrent BZD use occurred in 17% of opioid users (179 805/1 056 773). Overall, concurrent use was associated with higher risk of hospitalisation/ED visit (OR 1.13, p<0.001) and all cause death (OR 1.90; p<0.001). The estimated risk of hospitalisation/ED visit was highest in those >65 (OR 1.5; p<0.001), using multiple health providers (OR 1.67; p<0.001) and >365 days of opioid use (OR 1.76; p<0.001). Events due to opioid toxicity were also associated with concurrent use (OR 1.8; p<0.001). Opioid dose-response effects among concurrent patients who died were also noted (OR 3.13; p<0.001).

Interpretation: Concurrent use of opioids and BZDs further contributes to the risk of hospitalisation/ED visits and mortality in Alberta, Canada over opioid use alone, with higher opioid doses, older age and increased number of unique health providers carrying higher risks. Regulatory bodies and health providers should reinforce safe drug-use practices and be vigilant about coprescribing.