We thank Weinhandl1 for his comments regarding our analyses using the US Renal Data System of the association between gabapentin and pregabalin use and adverse outcomes among patients on hemodialysis.2 We acknowledge that we were limited in our ability to reliably capture benzodiazepine exposure with our available data, because benzodiazepines were not covered by Medicare Part D until 2013.3–5
Using more recent data from 2013, among a comparable cohort of 162,965 adult Medicare-covered patients on chronic hemodialysis with continuous Part D coverage during 2013, we found that the prevalence rates of gabapentin, pregabalin, and benzodiazepine use were 21% (n=33,900), 4% (n=7102), and 23% (n=37,112), respectively. The prevalence of benzodiazepine use is within the range that has been reported in prior studies involving patients on hemodialysis.6
Overall, the prevalence of concomitant use (defined as at least one instance of overlapping prescriptions in 2013) of gabapentin and benzodiazepine was 5.5% (n=8907), with a median overlap duration of 62 days (25th interquartile range, 28–152 days). Twenty-six percent of gabapentin users had concomitant benzodiazepine use, and 22% of gabapentin nonusers had concomitant benzodiazepine use. The prevalence of concomitant use of pregabalin and benzodiazepine was 1.3% (n=2054), with a median overlap duration of 57 days (interquartile range, 26–137 days). Twenty-nine percent of pregabalin users had concomitant benzodiazepine use, and 22% of pregabalin nonusers had concomitant benzodiazepine use.
Gabapentin and pregabalin use had virtually no association with benzodiazepine use on the basis of the point-biserial correlation (Table 1). The point-biserial correlation is mathematically equivalent to the Pearson correlation and can be interpreted on the same scale (0–0.5 is weak, 0.5–0.8 is moderate, and 0.8–1 is strong). Although Pearson correlations are not usually used for binary variables, such as medication exposure, they are, in fact, what a regression program uses to adjust one predictor for another one with a correlation of zero, indicating no adjustment.
Table 1.
Association between gabapentin and pregabalin use with benzodiazepine use
| Benzodiazepine Users (n=37,112), n (%) | Benzodiazepine Nonusers (n=125,853), n (%) | Correlationa | |
|---|---|---|---|
| Gabapentin users, n=33,900 | 8907 (26) | 24,993 (74) | 0.04 |
| Gabapentin nonusers, n=129,065 | 28,205 (22) | 100,860 (78) | |
| Pregabalin users, n=7102 | 2054 (29) | 5048 (71) | 0.03 |
| Pregabalin nonusers, n=155,863 | 35,058 (22) | 120,805 (78) |
Point-biserial correlation.
Correspondingly, the effect of benzodiazepine use on event rates would need to be massive to explain away the gabapentin or pregabalin associations. Thus, confounding by concomitant benzodiazepine use was unlikely to have had a large effect on our results. The letter of Weinhandl1 also mentions the possibility of unmeasured confounding by opioid use, and we would like to note that we adjusted for concomitant use of opioids in our analyses. We appreciate the interest in our research, and thank you for the opportunity to elaborate on our methodology.
Disclosures
None.
Acknowledgments
This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases grants K23DK103963 (to J.H.I.) and K24DK085153 (to K.L.J.), National Institute on Aging grants K24AG049057 (to M.A.S.) and P30 AG044281 (to M.A.S.), and the National Center for Advancing Translational Sciences, National Institutes of Health (NIH) through University of California, San Francisco Clinical and Translational Science Institute grants KL2 TR000143 and KL2 TR001870.
The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The funding organizations had no role in the study design; collection, analysis, and interpretation of the data; writing of the report; and decision to submit the article for publication. The data reported here have been supplied by the US Renal Data System. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government.
Footnotes
Published online ahead of print. Publication date available at www.jasn.org.
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