Lili Zhou1, Sandipan Bhattacharjee1, C Kent Kwoh2,3, Patrick J Tighe4, Gary M Reisfield5, Daniel C Malone6, Marion Slack1, Debbie L Wilson7, Ching-Yuan Chang7,8, Wei-Hsuan Lo-Ciganic7,8. 1. Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ, USA. 2. Department of Medicine, Division of Rheumatology, College of Medicine, University of Arizona, Tucson, AZ, USA. 3. University of Arizona Arthritis Center, College of Medicine, University of Arizona, Tucson, AZ, USA. 4. Department of Anesthesiology, College of Medicine, University of Florida, Gainesville, FL, USA. 5. Divisions of Addiction Medicine and Forensic Psychiatry, Departments of Psychiatry and Anesthesiology, College of Medicine, University of Florida, Gainesville, FL, USA. 6. Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA. 7. Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA. 8. Center for Drug Evaluation and Safety, College of Pharmacy, University of Florida, Gainesville, FL, USA.
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.
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.
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