Concomitant Use of Gabapentinoids with Opioids Is Associated with Increased Mortality and Morbidity among Dialysis Patients

Abstract

Background: The opioid epidemic is a public health emergency and appropriate medication prescription for pain remains challenging. Physicians have increasingly prescribed gabapentinoids for pain despite limited evidence supporting their use. We determined the prevalence of concomitant gabapentinoid and opioid prescriptions and evaluated their associations with outcomes among dialysis patients. Methods: We used the United States Renal Data System to identify patients treated with dialysis with Part A, B, and D coverage for all of 2010. Patients were grouped into 4 categories of drugs exposure status in 2010: (1) no prescriptions of either an opioid or gabapentinoid, (2) ≥1 prescription of an opioid and no prescriptions of gabapentinoids, (3) no prescriptions of an opioid and ≥1 prescription of gabapenbtinoids, (4) ≥1 prescription of both an opioid and gabapentinoid. Outcomes included 2-year all-cause death, dialysis discontinuation, and hospitalizations assessed in 2011 and 2012. Results: The study population included 153,758 dialysis patients. Concomitant prescription of an opioid and gabapentin (15%) was more common than concomitant prescription of an opioid and pregabalin (4%). In adjusted analyses, concomitant prescription of an opioid and gabapentin compared to no prescription of either was associated with increased risk of death (hazard ratio [HR] 1.16, 95% CI 1.12–1.19), dialysis discontinuation (HR 1.14, 95% CI 1.03–1.27), and hospitalization (HR 1.33, 95% CI 1.31–1.36). Concomitant prescription of an opioid and pregabalin compared to no prescription of either was associated with increased mortality (HR 1.22, 95% CI 1.16–1.28) and hospitalization (HR 1.37, 95% CI 1.33–1.41), but not dialysis discontinuation (HR 1.13, 95% CI 0.95–1.35). Prescription of opioids and gabepentinoids compared to only being prescribed opioids was associated with higher risk of hospitalizations, but not mortality, or dialysis discontinuation. Conclusions: Concomitant prescription of opioids and gabapentinoids among US dialysis patients is common, and both drugs have independent effects on outcomes. Future research should prospectively investigate the potential harms of such drugs and identify safer alternatives for treatment of pain in end-stage renal disease patients.