Trajectories of pregabalin use and their association with longitudinal changes in opioid and benzodiazepine use

Concomitant use of pregabalin with opioids and/or benzodiazepines is common, despite the increased risks. However, clinical trials suggest pregabalin can have an opioid-sparing effect when treating acute postoperative pain. We explored how opioid and benzodiazepine use changed over time in people initiating pregabalin, using dispensing claims data for a 10% sample of Australians (2013-19). Among 142,776 people initiating pregabalin (median age = 61 years, 57% female), we used group-based trajectory modelling to identify 6 pregabalin dose trajectories in the first year postinitiation. Two trajectories involved discontinuation: After one dispensing (49%), and after 6 months of treatment (14%). Four trajectories involved persistent use with variable estimated median daily doses of 39 mg (16%), 127 mg (14%), 276 mg (5%), and 541 mg (2%). We quantified opioid and benzodiazepine use in the year before and after pregabalin initiation using generalised linear models. Over the study period, 71% were dispensed opioids and 34% benzodiazepines, with people on the highest pregabalin dose having highest rates of use. Opioid use increased postpregabalin initiation. Among people using both opioids and pregabalin, the geometric mean daily dose in oral morphine equivalents increased after pregabalin initiation in all trajectories, ranging from +5.9% (99% confidence interval 4.8%-7.0%) to +39.8% (99% confidence interval 38.3%-41.5%) in people on the highest daily pregabalin dose. Among people using both pregabalin and benzodiazepines, the dose remained constant over time for people in all trajectories. Notwithstanding its reputation as opioid-sparing, in this outpatient setting, we observed that people using opioids tended to use higher opioid daily doses after pregabalin initiation, especially those on high pregabalin doses.