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

Introduction: Overuse of gabapentin and/or opioids occurs in a small percentage of patients at > 3-fold labeled dosages. Gabapentin may potentiate opioid effects.

Objective: The aim was to assess patient harm, defined as use of inpatient hospital (IPH) or emergency department (ED) services, associated with overuse of gabapentin with or without concomitant overuse of opioids.

Data Source: Data were sourced from the Truven Health MarketScan Commercial Claims and Encounters database, for the years 2013-2015.

Eligibility Criteria: The eligibility criteria were two or more claims (billed encounters) and ≥120 days of treatment with gabapentin and/or opioids.

Methods: Cohort identification was based on daily-dosage thresholds of 50 morphine-milligram equivalents and 3600 mg of gabapentin in a 12-month follow-up: (1) no overuse; (2) mild overuse (two or more claims or two or fewer calendar quarters over threshold); and (3) sustained overuse (three or more over-threshold calendar quarters). IPH and ED use were measured for 6 months after the first overuse date (cohorts 2 and 3) or a randomly assigned date (cohort 1). Logistic regression analyses controlled for pre-treatment IPH/ED utilization, indication, addiction diagnosis, concomitant sedative/hypnotic use, and demographics.

Results: All-cause and drug-related IPH/ED utilization increased monotonically with degree of overuse, particularly of more than one medication. Sustained overuse of gabapentin multiplied odds of all-cause IPH by 1.366 [95% confidence interval (CI) 1.055-1.769], drug-related IPH by 1.440 (95% CI 1.010-2.053), and IPH/ED for altered mental status (e.g., euphoria, anxiety) by 1.864 (95% CI 1.324-2.624). Sustained overuse of both medications quadrupled odds of all-cause IPH, drug-related IPH, and IPH/ED for altered mental status or respiratory depression.

Conclusion: Despite modest effects of gabapentin overuse alone, overuse of gabapentin with opioids may increase risk of harm and health-service utilization, supporting calls to make gabapentin a controlled substance in the USA.