Adverse outcomes associated with concurrent gabapentin, opioid, and benzodiazepine utilization: A nested case-control study

Background Gabapentin, opioids, and/or benzodiazepines are commonly prescribed for a variety of pain and psy-chiatric conditions. Despite the high likelihood of co-prescription of these medications, little is known about co -utili-zation of gabapentin (GABA), opioids (OP), and benzodiazepines (BZD) and associated public health outcomes.Methods Using Medicare CCW Data, 2013-2016, we conducted a nested case-control study to examine the associa-tion between concurrent utilization of GABA, OP, and BZD and respiratory depression, opioid, and substance -related overdose among Medicare disabled beneficiaries. Cases and controls were Fee-for-service disabled beneficia-ries who had a diagnosis of acute pain (AP), chronic pain (CP) or mental health conditions (MH) and received GABA, OP or BZD. Cases with respiratory depression, opioid or substance-related overdose were matched with up to 4 controls on socio-demographics, year of cohort entry and disease risk score. Primary exposure was concurrent medication utilization defined as an overlap of at least one day in prescriptions for GABA, OP and BZD. Findings Across all cohorts, the majority of cases and controls were under 65, female, dually eligible and had prior histories of pain and mental health conditions. GABA+OP+BZD use was associated with increased odds of respira-tory depression [AOR(95%CI)-AP: 1.35 (1.19-1.52), CP:1.24 (1.11-1.38) and MH: 1.16 (1.02-1.32) vs. OP only], opioid-related overdose [AP: 1.43 (1.04-1.98), CP: 1.47 (1.07-2.00) and MH: 1.44 (1.04-2.00) vs. OP only], and substance -related overdose [AP: 1.77 (1.26-2.50), CP: 1.70 (1.24-2.34) and MH: 1.92 (1.31-2.82) vs. GABA only]. While there were cohort differences in the association between GABA+OP and both respiratory depression and opioid-related overdose, GABA+OP and GABA+BZD use were associated with significantly higher odds of substance-related over-dose across all clinical cohorts.Interpretation Among Medicare disabled beneficiaries, concurrent utilization of gabapentin, opioids, and benzodia-zepines is associated with multiple adverse outcomes. Given this, it is imperative that the benefits and risks of co -prescribing these medications be comprehensively examined.