Background: Systemic muscle relaxant prescriptions have risen in United States. Baclofen is a commonly prescribed muscle relaxant that is gamma-aminobutyric acid (GABA) agonist and renally cleared. We aimed to determine the risk of encephalopathy and mortality associated with baclofen compared to an alternate muscle relaxant cyclobenzaprine in a real-world setting.
Methods: We conducted a retrospective cohort study of adults who received a new prescription for baclofen or cyclobenzaprine between January 2005 and December 2018 using a tertiary health system data from Geisinger Health, Pennsylvania, United States. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance baclofen users and cyclobenzaprine users on 45 characteristics including demographics, comorbidities, and concomitant prescriptions. Unbalanced characteristics after applying IPTW were included as a regression covariate. Fine-Gray competing risk and Cox proportional hazards models were used to estimate the risk of encephalopathy and mortality, respectively. We additionally assessed the risks of encephalopathy and mortality in prespecified subgroup defined by estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 and ≥60 ml/min/1.73 m2.
Results: The study cohort included 9,366 new baclofen users and 50,236 new cyclobenzaprine users. Mean age was 52.8 years and 61% were female. Musculoskeletal diagnoses and concomitant opioid prescriptions were prevalent at 66% and 40%, respectively. All covariates, except year of cohort entry, were well balanced between the two groups after applying IPTW. Baclofen vs. cyclobenzaprine use was associated an increased risk of encephalopathy at 30 days (IPTW incidence rate per 1,000 person-years, 52.3 vs. 22.2; IPTW hazard ratio [HR], 2.35; 95% confidence interval [CI], 1.59–3.48). The risk of encephalopathy persisted at 90 days, 180 days, and up to 1 year after medication initiation (1-year IPTW HR, 1.94; 95% CI, 1.56–2.40; Table 1). There was a higher risk of mortality associated with baclofen vs. cyclobenzaprine use at 30 days (IPTW incidence rate per 1,000 person-years, 36.4 vs. 19.8; IPTW HR, 1.85; 95% CI, 1.17–2.93). The mortality risk remained increased through 90 days, 180 days, and 1 year after prescription (1-year IPTW HR, 1.42; 95% CI, 1.20–1.67; Table 1). The 1-year risks of encephalopathy and mortality were similar across subgroups of eGFR < 60 and ≥60 ml/min/1.73 m2 (interaction P = 0.23 and 0.22, respectively).
Conclusions: Baclofen compared to cyclobenzaprine use was associated with higher risks of encephalopathy and mortality as early as 30 days following initiation. The risks of encephalopathy and mortality persisted through 1 year following initial prescription. The real-world risks associated with baclofen found in the routine care setting have the potential to inform prescribing practice and clinical decision making.
