High-dose use of pregabalin and gabapentin in France: a retrospective, population-based cohort study

Following recent developments regarding gabapentinoid (i.e., pregabalin and gabapentin) abuse and misuse in France, this study aims to describe new users of gabapentinoids from 2017 to 2021, estimate the incidence of high-dose use, and identify the associated factors.

We used the French National Health Data System. In this retrospective, population-based cohort study, we included new users of pregabalin and gabapentin, aged 18 years and older, in two separate cohorts. We defined new users as patients with at least three dispensings of either pregabalin or gabapentin within a 12-month period, with the first dispensing occurring from January 1, 2017 to December 31, 2021, and no dispensing in the previous 12 months. We used high-dose use as a proxy for potential abuse and misuse. We defined high-dose use as exposure to an average daily dose exceeding the maximum recommended dose. We followed patients for up to 24 months. Then, we calculated the cumulative incidence of high-dose use in each cohort. Finally, we identified factors associated with high-dose use in each cohort using Cox models.

We included 898,887 new users of pregabalin and 271,832 new users of gabapentin. Since 2020, the monthly number of new users of pregabalin has decreased and the monthly number of new users of gabapentin has increased. In both cohorts, the median age was 64 years, and about 60% of patients were women. Incidence rates were 26.0 [95% CI: 25.8, 26.3] per 1000 person-years for high-dose use of pregabalin and 10.0 [9.7, 10.3] per 1000 person-years for high-dose use of gabapentin. During treatment episodes where high-dose use was identified, patients in the pregabalin cohort used higher daily doses than those in the gabapentin cohort. The main factors associated with high-dose use of pregabalin and gabapentin included prior exposure to the other gabapentinoid, prior exposure to opioid agonist treatments, prior exposure to strong opioid analgesics, younger age, being a man, paraplegia, active cancers, and higher number of prescribers.

Prescribers should exercise extra caution when initiating gabapentinoids in patients at risk of high-dose use.

This study is part of the METEOR study, which was funded by EPI-PHARE (https://www.epi-phare.fr/).