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Original Investigation
November 9, 2019

Association of Baclofen With Encephalopathy in Patients With Chronic Kidney Disease

Author Affiliations
  • 1Institute for Clinical Evaluative Sciences, London, Ontario, Canada
  • 2Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
  • 3Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada
JAMA. 2019;322(20):1987-1995. doi:10.1001/jama.2019.17725
Key Points

Question  Is there an increased risk of encephalopathy among patients with chronic kidney disease (CKD) initiating treatment with a higher vs lower dose of baclofen?

Findings  In this retrospective cohort study that included 15 942 patients with CKD, the 30-day incidence of encephalopathy among those prescribed baclofen at greater than or equal to 20 mg per day compared with less than 20 mg per day was 1.11% vs 0.42%, a difference that was statistically significant.

Meaning  Baclofen use among patients with CKD, particularly at higher doses, may be associated with an increased risk of encephalopathy.

Abstract

Importance  At least 30 case reports have linked the muscle relaxant baclofen to encephalopathy in patients with chronic kidney disease (CKD).

Objective  To compare the 30-day risk of encephalopathy in patients with CKD and newly prescribed baclofen at greater than or equal to 20 mg per day vs less than 20 mg per day. The secondary objective was to compare the risk of encephalopathy in baclofen users vs nonusers.

Design, Setting, and Participants  Retrospective population-based cohort study in Ontario, Canada (2007-2018) using linked health care data. Participants comprised 15 942 older adults (aged 66 years or older) with CKD (defined as an estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 but not receiving dialysis). The primary cohort was restricted to patients who were newly prescribed baclofen; participants in the secondary cohort were new users and nonusers.

Exposures  Prescription for oral baclofen greater than or equal to 20 mg per day vs less than 20 mg per day.

Main Outcomes and Measures  Hospital admission with encephalopathy, defined as a main diagnosis of delirium, disorientation, transient alteration of awareness, transient cerebral ischemic attack, or unspecified dementia within 30 days of starting baclofen. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RRs) were obtained using modified Poisson regression and weighted risk differences (RDs) using binomial regression. Prespecified subgroup analyses were conducted by eGFR category.

Results  The primary cohort comprised 15 942 patients with CKD (9699 [61%] women; median age, 77 years [interquartile range, 71-82]; 9707 [61%] patients started baclofen at ≥20 mg/d and 6235 [39%] at <20 mg/d). The primary outcome, hospitalization with encephalopathy, occurred in 108/9707 (1.11%) patients who started baclofen at greater than or equal to 20 mg per day and in 26/6235 (0.42%) who started baclofen at less than 20 mg per day; weighted RR, 3.54 (95% CI, 2.24 to 5.59); weighted RD, 0.80% (95% CI, 0.55% to 1.04%). In subgroup analysis, the absolute risk increased progressively at lower eGFR (weighted RD eGFR 45-59, 0.42% [95% CI, 0.19%-0.64%]; eGFR 30-44, 1.23% [95% CI, 0.62%-1.84%]; eGFR <30, 2.90% [95% CI, 1.30%-4.49%]; P for interaction, <.001]). In the secondary comparison with 284 263 nonusers, both groups of baclofen users had a higher risk of encephalopathy (<20 mg/d weighted RR, 5.90 [95% CI, 3.59 to 9.70] and ≥20 mg/d weighted RR, 19.8 [95% CI, 14.0 to 28.0]).

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

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