LAUSR

We appreciate the letter by Bonnet et al. [1] regarding the relative risks of gabapentinoid misuse versus alternative agents, as well as limitations of available evidence. Having read their previous works regarding gabapentinoid misuse [2–4], we acknowledge the distinction between true psychological addiction versus misuse potential related to hedonistic (e.g. euphoria) or therapeutic (e.g. amelioration of undertreated pain or withdrawal) effects and concur with their sentiment that limited evidence exists confirming significant addiction risk. As such, our systematic review (SR) [5] did not assert that gabapentinoids are highly addictive, but rather that they fall into the latter category and are increasingly being misused. We also agree that discussion of gabapentinoid risks must be considered in the context of alternative options; therefore, we reiterate that we are not calling for sweeping reduction in their clinical use. However, we would contend that the growing body of evidence regarding potential harms associated with gabapentinoids, particularly when used alongside opioids, warrants re-evaluation of the risk–benefit profile among at-risk patients [5, 6]. Although we concur that there are limitations to currently published gabapentinoid misuse studies, as elucidated within our paper, we oppose the assertion of Bonnet et al. that such studies should be marginalized in lieu of unavailable controlled clinical studies, for several reasons. First, large-scale, prospective, randomized studies of gabapentinoid misuse risks are unlikely to be conducted given the potential ethical and safety concerns and difficulty obtaining funding for large-scale studies at this stage of the patent life-cycle. However, small clinical studies have identified gabapentinoid drug-liking effects to be of similar magnitude to diazepam [7] and tetrahydrocannabinol [8], and considerable qualitative research provides anecdotal evidence of their misuse liability from many with a history of gabapentinoid misuse [5, 6]. Instead, we assert that prospective clinical studies of gabapentinoid misuse should be one part of a multimodal approach to assessing this issue. While many of the individual articles on their own may offer limited generalizability, these limitations are attenuated by studying the subject from a variety of methodologies and populations and assessing the cumulative body of evidence to draw conclusions, as has been done in our SRs [5, 6] which included evidence from 114 novel studies. Thus, despite the limited prospective clinical evidence available, the cumulative body This letter replies to the article available at https:// doi. org/ 10. 1007/ s4026502001432-7.