Higher baclofen dosage associated with encephalopathy in older patients with CKD

Older patients with chronic kidney disease (CKD) and new prescriptions of baclofen may be at increased risk for encephalopathy at higher dosages versus lower dosages, a recent study found.

Researchers used linked health care data to perform a retrospective population-based cohort study in Ontario, Canada, among older adults with chronic kidney disease, defined as an estimated glomerular filtration rate (GFR) below 60 mL/min/1.73 m² but no dialysis. The goal of the study was to compare risk for encephalopathy over 30 days in patients with CKD who were newly prescribed 20 mg or more of baclofen per day and those prescribed less than 20 mg/d, as well as risk for encephalopathy in patients who were taking baclofen versus those who were not. At least 20 mg of baclofen per day is the median dosage that has been reported in cases of baclofen toxicity among CKD patients.

The primary cohort included only patients who had been newly prescribed baclofen, while the secondary cohort included both new users and nonusers. The study's main outcome measures were hospital admission with encephalopathy, which was defined as a main diagnosis of delirium, disorientation, transiently altered awareness, transient cerebral ischemic attack, or unspecified dementia within 30 days of starting therapy with baclofen. Results of the study were published Nov. 9 by JAMA.

Overall, 15,942 patients from 2007 to 2018 who were at least 66 years of age were included in the primary cohort. The median age was 77 years, and 9,699 (61%) were women. Estimated GFRs were between 45 and 59 mL/min/1.73 m² in 66% of patients, between 30 and 45 mL/min/1.73 m² in 27% of patients, and below 30 mL/min/1.73 m² in 7% of patients. Patients were more likely to start baclofen at a higher dosage of 20 mg/d or greater (60.9%) than at a lower dosage (39.1%). In the high-dosage group, 108 of 9,707 (1.11%) were hospitalized with encephalopathy versus 26 of 6,235 (0.42%) in the low-dosage group (weighted risk ratio [RR], 3.54 [95% CI, 2.24 to 5.59]; weighted risk difference [RD], 0.80% [95% CI, 0.55% to 1.04%]). A total of 165 of 284,263 patients who had not taken baclofen (0.06%) were admitted to the hospital for encephalopathy. Both high- and low-dosage baclofen users had a higher risk for encephalopathy than nonusers (weighted RR, 5.90 [95% CI, 3.59 to 9.70] for <20 mg/d and 19.8 [95% CI, 14.0 to 28.0] for ≥20 mg/d).

The researchers noted that their study was observational and that their results need to be replicated. In addition, they pointed out that it was not known whether patients took their medications as prescribed and that their results cannot be generalized to younger patients, among other limitations. They concluded that 30-day incidence of encephalopathy was higher in older patients with CKD who had been newly prescribed a higher versus lower dosage of baclofen, confirming and extending the findings of 30 previous case reports that linked baclofen with encephalopathy in this population. However, they wrote, “This study was not designed to answer the question of whether the potential benefits of baclofen outweigh its risks, and clinicians will need to judge this on a patient-by-patient basis.”