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

Abisola Olopoenia; Wendy Camelo-Castillo; Danya M Qato; Adepeju Adekoya; Frank Palumbo; Leah Sera; Linda Simoni-Wastila

doi:10.1016/j.lana.2022.100302

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

Lancet Reg Health Am. 2022 Jun 23:13:100302. doi: 10.1016/j.lana.2022.100302. eCollection 2022 Sep.

Authors

Abisola Olopoenia¹, Wendy Camelo-Castillo¹, Danya M Qato^{1

2}, Adepeju Adekoya³, Frank Palumbo¹, Leah Sera⁴, Linda Simoni-Wastila^{1

5}

Affiliations

¹ Department of Pharmaceutical Health Services Research, University of Maryland Baltimore, Baltimore, MD, USA.
² School of Medicine, University of Maryland Baltimore, Baltimore, MD, USA.
³ Johns Hopkins Medicine, Department of Anesthesiology & Critical Care Medicine, Division of Chronic Pain Medicine, Baltimore, MD, USA.
⁴ Department of Pharmacy Practice and Science, University of Maryland Baltimore, Baltimore, MD, USA.
⁵ Peter Lamy Center on Drug Therapy and Aging, University of Maryland Baltimore, Baltimore, MD, USA.

Abstract

Background: Gabapentin, opioids, and/or benzodiazepines are commonly prescribed for a variety of pain and psychiatric conditions. Despite the high likelihood of co-prescription of these medications, little is known about co-utilization 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 association 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 beneficiaries 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 respiratory 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 overdose across all clinical cohorts.

Interpretation: Among Medicare disabled beneficiaries, concurrent utilization of gabapentin, opioids, and benzodiazepines is associated with multiple adverse outcomes. Given this, it is imperative that the benefits and risks of co-prescribing these medications be comprehensively examined.

Funding: None.

Keywords: Benzodiazepine; Gabapentin; Mental health; Opioids; Pain.