Dual‐trajectories of opioid and gabapentinoid use and risk of subsequent drug overdose among Medicare beneficiaries in the United States: a retrospective cohort study

Abstract

Background and aims Little is known about opioid and gabapentinoid (OPI‐GABA) use duration and dose patterns’ associations with adverse outcome risks. We examined associations between OPI‐GABA dose and duration trajectories and subsequent drug overdose. Design Retrospective cohort study. Setting US Medicare. Participants Using a 5% sample (2011–16), we identified 71 005 fee‐for‐service Medicare beneficiaries with fibromyalgia, low back pain, neuropathy and/or osteoarthritis initiating OPIs and/or GABAs [mean age ± standard deviation (SD) = 65.5 ± 14.5 years, female = 68.1%, white = 76.8%]. Measurements Group‐based multi‐trajectory models identified distinct OPI‐GABA use patterns during the year of OPI and/or GABA initiation, based on weekly average standardized daily dose (i.e. OPIs = morphine milligram equivalent, GABAs = minimum effective daily dose). We estimated models with three to 12 trajectories and selected the best model based on Bayesian information criterion (BIC) and Nagin's criteria. We estimated risk of time to first drug overdose diagnosis within 12 months following the index year, adjusting for socio‐demographic and health factors using inverse probability of treatment weighted multivariable Cox proportional hazards models. Findings We identified 10 distinct trajectories (BIC = –1 176 954; OPI‐only = 3, GABA‐only = 3, OPI‐GABA = 4). Compared with OPI‐only early discontinuers (40.6% of the cohort), 1‐year drug overdose risk varied by trajectory group: consistent low‐dose OPI‐only users [16.6%; hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.19–1.82], consistent high‐dose OPI‐only users (1.8%; HR = 4.57, 95% CI = 2.99–6.98), GABA‐only early discontinuers (12.5%; HR = 1.39, 95% CI = 1.09–1.77), consistent low‐dose GABA‐only users (11.0%; HR = 1.44, 95% CI = 1.12–1.85), consistent high‐dose GABA‐only users (3.1%; HR = 1.43, 95% CI = 0.94–2.17), early discontinuation of OPIs and consistent low‐dose GABA users (6.9%; HR = 1.24, 95% CI = 0.90–1.69), consistent low‐dose OPI‐GABA users (3.4%; HR = 2.49, 95% CI = 1.76–3.52), consistent low‐dose OPI and high‐dose GABA users (3.2%; HR = 2.46, 95% CI = 1.71–3.53) and consistent high‐dose OPI and moderate‐dose GABA users (0.9%; HR = 7.22, 95% CI = 4.46–11.69). Conclusions Risk of drug overdose varied substantially among US Medicare beneficiaries on different use trajectories of opioids and gabapentinoids. High‐dose opioid‐only users and all consistent opioid and gabapentinoid users (regardless of doses) had more than double the risk of subsequent drug overdose compared with opioid‐only early discontinuers.

Investigating the prescribing trajectory and geographical drug utilisation patterns of gabapentinoids in primary care in England: An ecological study

“…36,37 GBTM has been widely applied to clinical research, including drug utilisation studies. 38,39 Practices were divided into groups by GBTM based on their trend in longitudinal quarterly prescribing of gabapentinoids after removing extreme values. The estimated average quarterly prescribing trend of each group from GBTM was presented graphically, and the group membership was mapped geographically.…”

“…Group‐based trajectory model (GBTM) is a finite mixture model approach applied to categorise study subjects into groups accounting for the dynamic nature of an outcome that is repeatedly measured over time 36,37 . GBTM has been widely applied to clinical research, including drug utilisation studies 38,39 . Practices were divided into groups by GBTM based on their trend in longitudinal quarterly prescribing of gabapentinoids after removing extreme values.…”

Association Between Dual Trajectories of Opioid and Gabapentinoid Use and Healthcare Expenditures Among US Medicare Beneficiaries

“…This cross-sectional study included fee-for-service beneficiaries with fibromyalgia, low back pain, neuropathy, or osteoarthritis, identified from $1 inpatient or $2 other medical claims on different days using the International Classification of Diseases codes (see Appendix Table 1 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2020.12.001 for International Classification of Diseases, ninth Revision, Clinical Modification/ International Classification of Diseases, 10th Revision, Clinical Modification codes). 26,31 This study focused on the chronic pain conditions that are either the FDA-approved indications (ie, fibromyalgia and neuropathy) for gabapentinoids or in which gabapentinoids are commonly prescribed (ie, low back pain and osteoarthritis), as done in a prior study 24,32,33 This study restricted the analytical sample to the beneficiaries newly initiating opioids or gabapentinoids, defined as those with no opioid or gabapentinoid prescriptions within 6 months prior to the index date (ie, date of the first prescription for either opioids or gabapentinoid, whichever occurred first) (see Appendix Fig. 1 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2020.12.…”

“…3 Several recent studies showed that concurrent opioid and gabapentinoid (hereafter OPI-GABA) use was associated with an increased risk of opioid-related deaths and other adverse outcomes (eg, hospitalizations and mortality). [20][21][22][23][24] According to the 2019 updated American Geriatrics Society Beers Criteria for potentially inappropriate medication use in older adults, it is recommended to avoid OPI-GABA use, except when (1) transitioning from opioid therapy to gabapentinoids, or (2) using gabapentinoids to reduce opioid dose. 25 Therefore, concurrent OPI-GABA use may increase the occurrence of adverse health outcomes, resulting in increased healthcare expenditures.…”

Commentary on Zhou et al. : Policy levers to reduce co‐prescribing of opioids and gabapentinoids and overdose risk

“…However, little is known about how concurrent use of opioids and gabapentinoids, which are commonly prescribed in the United States, contributes to overdose risk. In this issue, Zhou et al [1] tackle this question using a random sample of US Medicare patients with conditions for which gabapentinoids have gained US Food and Drug Administration (FDA) approval (fibromyalgia, neuropathy) and conditions for which gabapentinoids are frequently prescribed in the absence of FDA approval (low back pain, osteoarthritis). The authors used group-based multi-trajectory models of weekly doses of opioids and/or gabapentinoids, identified 10 unique trajectory groups and examined their association with overdose events measured in Medicare claims in the following year.…”