Gabapentin Use Among Individuals Initiating Buprenorphine Treatment for Opioid Use Disorder

Abstract

Importance: Gabapentin prescriptions have drastically increased in the US due to off-label prescribing in settings such as opioid use disorder (OUD) treatment to manage a range of comorbid conditions and withdrawal symptoms, despite a lack of evidence.

Objective: To assess the purpose and associated risks of off-label gabapentin use in OUD treatment.

Design, setting, and participants: This retrospective recurrent-event case-control study with a crossover design used administrative claims data from MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Individuals aged 12 to 64 years with an OUD diagnosis and filling buprenorphine prescriptions were included in the primary analysis conducted from July 1, 2022, through June 1, 2023. Unit of observation was the person-day.

Exposures: Days covered by filled gabapentin prescriptions.

Main outcomes and measures: Primary outcomes were receipt of gabapentin in the 90 days after initiation of buprenorphine treatment and drug-related poisoning. Drug-related poisonings were defined using codes from International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.

Results: A total of 109 407 patients were included in the analysis (mean [SD] age, 34.0 [11.2] years; 60 112 [54.9%] male). Among the 29 967 patients with Medicaid coverage, 299 (1.0%) were Hispanic, 1330 (4.4%) were non-Hispanic Black, 23 112 (77.1%) were non-Hispanic White, and 3399 (11.3%) were other. Gabapentin was significantly less likely to be prescribed to Black or Hispanic patients, and more likely to be prescribed to female patients, those with co-occurring substance use or mood disorders, and those with comorbid physical conditions such as neuropathic pain. Nearly one-third of persons who received gabapentin (4336 [31.1%]) had at least 1 drug-related poisoning after initiating buprenorphine treatment, compared with 13 856 (14.5%) among persons who did not receive gabapentin. Adjusted analyses showed that days of gabapentin use were not associated with hospitalization for drug-related poisoning (odds ratio, 0.98 [95% CI, 0.85-1.13]). Drug-related poisoning risks did not vary based on dosage.

Conclusions and relevance: Gabapentin is prescribed in the context of a myriad of comorbid conditions. Even though persons receiving gabapentin are more likely to have admissions for drug-related poisoning, these data suggest that gabapentin is not associated with an increased risk of drug-related poisoning alongside buprenorphine in adjusted analyses. More data on the safety profile of gabapentin in OUD settings are needed.

Figure 1.. Derivation of the Analytic Sample

Figure 2.. Risk Factors Associated With Gabapentin Receipt Between Initiation of Buprenorphine Treatment and 90 Days After Initiation

A multivariate Poisson regression model shows the risk factors associated with gabapentin receipt between time 0 (initiation date) and 90 days after initiation. The x-axis shows the adjusted risk ratio (aRR) for gabapentin receipt, with the left side representing lower aRRs for gabapentin receipt and the right side showing higher aRRs for gabapentin receipt. SUD indicates substance use disorder.

Figure 3.. Association Between Person-Days of Gabapentin or Buprenorphine Treatment and Drug-Related Poisonings Among Persons With Opioid Use Disorder Receiving Buprenorphine

Model A estimates the association of person-days of gabapentin (of any dosage) and buprenorphine receipt with admissions for drug-related poisoning; model B, with restriction to gabapentin at 900 mg/d or greater; and model C, with restriction to gabapentin at 1800 mg/d or greater. The x-axis shows the odds ratio (OR) for drug-related poisoning risk, with the left side representing lower poisoning risk and the right side showing greater poisoning risk.