Risk for Encephalopathy in Patients With Chronic Kidney Disease Using Baclofen

Initiating baclofen treatment at a high dose may be associated with increased 30-day incidence of encephalopathy in older adults with chronic kidney disease (CKD), according to study results published in JAMA.

Baclofen is used as a muscle relaxant in patients with spasticity, but may also be used for other indications, including alcoholism, gastroesophageal reflux disease, nystagmus, and trigeminal neuralgia. Because baclofen is eliminated primarily by the kidneys, it may be associated with adverse events in patients with CKD. There are roughly 30 case reports that link baclofen treatment to encephalopathy in patients with CKD, shortly after instituting the treatment.

The goal of the study was to assess the risk for encephalopathy in patients with CKD and newly prescribed baclofen at a daily dose of >20 mg compared with a lower daily dose. The primary outcome was hospitalization for encephalopathy, defined as a main diagnosis of delirium, disorientation, transient alteration of awareness, transient cerebral ischemic attack, or unspecified dementia.

The retrospective population-based cohort study included 15,942 patients aged >66 years with CKD (CKD was defined as having an estimated glomerular filtration rate <60 mL/min/1.73m², but not receiving dialysis). All patients were newly treated with baclofen, including 9707 patients (mean age 76.5 years, 41.1% men) who received a high dose (≥20 mg/day, median 30 mg/day) and 6235 patients (mean age 78 years, 36.2% men) who received a low dose (<20 mg/day, median 10 mg/day).

The risk for hospitalization with encephalopathy was significantly greater in patients who started baclofen at a high dose (108/9707 patients; 1.11%), compared with patients who started at a low dose (26/6235 patients; 0.42%) baclofen (weighted risk ratio [RR] 3.54; 95% CI, 2.24-5.59; weighted risk difference 0.80%; 95% CI, 0.55%-1.04%). Compared with initiating baclofen at a low dose, starting at a high daily dose was associated with an increased risk for hospitalization as a result of delirium, as well as all-cause hospitalization, but not all-cause mortality. Results were consistent in multiple sensitivity analyses and when alternative definitions of encephalopathy were analyzed.

In a secondary comparison of patients who had no history of baclofen use, both low-dose and high-dose baclofen use had a greater risk for encephalopathy (weighted RR, 5.90; 95% CI, 3.59-9.70; weighted risk difference, 0.35%; 95% CI, 0.18%-0.51%. vs weighted RR, 19.8; 95% CI, 3.59-9.70; weighted risk difference, 1.06%; 95% CI, 0.85%-.27%).

The researchers acknowledged several study limitations, including the observational design, limiting the cohort to patients aged >66 years, and the outcome evaluation based on diagnostic codes recorded in the administrative database. Further, the study focused on baclofen dispensing, but there was no available data on actual use of the medication.

“Among older patients with CKD who were newly prescribed baclofen, the 30-day incidence of encephalopathy was increased among those prescribed higher compared with lower doses. If verified, these risks should be balanced against the benefits of baclofen use,” concluded the researchers.

Reference

Muanda FT, Weir MA, Bathini L, et al. Association of baclofen with encephalopathy in patients with chronic kidney disease [published online November 9, 2019]. JAMA. doi:10.1001/jama.2019.17725