Letter to the Editor: Future Analyses of Gabapentin Use

TO THE EDITOR

Lanham et al.’s thoughtful article “Gabapentin Presents High Potential for Misuse” in the 11/24/2022 online issue of Pharmacy Times addresses the potential for gabapentin use to potentiate the risk of opioid overdose. We write to comment on two items regarding their analysis.

1. Misclassification. The authors cite a study by Peckham et al. analyzing risks associated with concomitant use of gabapentin and opioid products.¹ Specifically, the cited article uses the term “overuse” of gabapentin and/or opioids, defined as prescribed daily dosages exceeding a predetermined threshold. The authors, however, characterize the receipt of both medication classes above certain dosages as “co-abuse.”

The receipt of medication dosages above a particular value does not necessarily indicate medication abuse. Implying otherwise could confuse readers about the exposures and outcomes studied in the cited article.

2. Confounding by indication. Gabapentin is doubtless contributory to many fatal opioid-involved overdoses. That said, in the analysis by Lanham et al., there is a confounder that is not acknowledged: chronic pain. Gabapentin may be prescribed in lieu of (or in tandem with) opioid prescriptions to manage certain types of chronic pain.

Patients with more severe chronic pain may be more likely than patients with less severe chronic pain to be prescribed both gabapentin and higher doses of opioids – the latter a known independent risk factor for overdose.² In this patient population, the risk attributable to gabapentin in assessing opioid-involved overdoses where gabapentin is detected may be challenging to assess.

Gabapentin offers both advantages and disadvantages to patients depending on the clinical scenario. There are clearly risks associated with concomitant use of gabapentin and other CNS depressants such as opioids, and these risks should be taken seriously. We applaud Lanham et al.’s insightful review of the regulatory components of this topic, and recommend future analyses consider the potential for misclassification and confounding by indication so readers can appreciate the nuances of – and challenges associated with – epidemiology in this space.

References

1. Peckham AM, Fairman KA, Sclar DA. All-cause and drug-related medical events associated with overuse of gabapentin and/or opioid medications: a retrospective cohort analysis of a commercially insured US population. Drug Saf. 2018;41(2):213-228. doi:10.1007/s40264-017-0595-1
2. Coyle DT, Pratt CY, Ocran-Appiah J, Secora A, Kornegay C, Staffa J. Opioid analgesic dose and the risk of misuse, overdose, and death: A narrative review. Pharmacoepidemiol Drug Saf. 2018 May;27(5):464-472. doi: 10.1002/pds.4366