Back Off the Baclofen: Increased Risk of Encephalopathy
Dr. Sata
Clinical question: Compared to other muscle relaxants, does baclofen increase the risk of encephalopathy?
Background: Baclofen is a GABAergic muscle relaxant that is useful for patients with neuromuscular disorders including spasticity. It is also prescribed for low back pain, similar to cyclobenzaprine and tizanidine. It is known that, as baclofen is primarily renally excreted, it should not be used in patients with chronic kidney disease (CKD) due to the risk of encephalopathy. However, it is not known if this risk is shared by all these medications or in patients without CKD.
Study design: Retrospective cohort study
Setting: Tertiary health system administrative data over 13 years
Synopsis: Over the study period there were two active-comparator cohorts created of adult patients: Cohort 1, 16,192 new baclofen users versus 9,782 new tizanidine users, and Cohort 2, 9,330 new baclofen users versus 50,076 new cyclobenzaprine users. To address potential confounding, the authors applied a logistic regression model using demographics, comorbidities, and medication interactions to achieve inverse probability treatment weighting (IPTW). The 30-day risk of encephalopathy was higher in patients treated with baclofen compared with tizanidine (IPTW incidence rate per 1,000 person-years, 64.7 versus 28.3, subdistribution HR, 2.29; 95% CI, 1.43 to 3.67) and compared with those treated with cyclobenzaprine (52.6 versus 22.3, subdistribution HR, 2.35; 95% CI, 1.59 to 3.48). The increased risk of encephalopathy with the new use of baclofen over cyclobenzaprine and tizanidine persisted over the first year of treatment. A limitation of the study was the reliance on coding data to quantify rates of encephalopathy and the use of prescription fill data as a surrogate for medication use and adherence.
Bottom line: Baclofen initiation is associated with a higher risk of encephalopathy compared to other common muscle relaxants, and caution should be used when selecting this medication over tizanidine or cyclobenzaprine.
Citation: Hwang YJ, Chang AR, et al. Baclofen and the risk of encephalopathy: a real-world, active-comparator cohort study. Mayo Clin Proc. 2023;98(5):676-688.
Dr. Sata is a hospitalist at Duke University Hospital and an associate professor of medicine at Duke University School of Medicine in Durham, N.C. n