Letter to the Editor The Journal of Clinical Pharmacology 2021, 61(6) 836–837 © 2021, The American College of Clinical Pharmacology DOI: 10.1002/jcph.1843 Association Between Baclofen and Respiratory Depression in Patients With Chronic Kidney Disease Satoru Mitsuboshi, PhD Keywords adverse event, baclofen, chronic kidney disease, respiratory depression Baclofen is used to manage spasticity and treat alcohol use disorder. 1,2 However, because baclofen is eliminated mainly via the kidneys, 3 users with chronic kidney disease (CKD) have a high risk of adverse events, most notably encephalopathy. 4 Respiratory depression is another serious adverse event caused by baclofen, and a case report suggested that baclofen caused respiratory depression in a patient with CKD. 5–7 Although the risk of respiratory depression caused by baclofen has not been quantifed, drug-induced respiratory depression is generally recognized as a serious adverse event that may even lead to death. 8 In this study, data from the Japanese Adverse Drug Event Report (JADER) was used to evaluate whether baclofen increases the risk of respiratory depression in patients with CKD. This was an observational study using anonymized patient data recorded in JADER, and thus institutional review board review and approval was not required. Data recorded from April 2004 to May 2020 were downloaded from the Pharmaceuticals and Medical Devices Agency website (http://www.pmda.go.jp/) on November 3, 2020. Inclusion criteria were all oral baclofen and eperisone users regardless of whether the data reporter suspected a possible adverse event. Eperisone was set as the control because it is used to manage spasticity. Exclusion criteria were patients who used both baclofen and eperisone. Patients with missing data on sex, age, or body weight were also excluded. Respiratory depression was defned as reporting res- piratory failure or respiratory depression. CKD was defned as reporting a comorbidity of CKD, kidney failure, and use of dialysis. Multiple logistic regression analysis was used to assess whether use of baclofen in patients with CKD is a risk factor for respiratory depression. Sex, age, body weight, and presence of CKD were considered in the analysis. Modeling was based on a complete-case analysis. Statistical analysis was performed using R version 3.4.1 (R Foundation for Statistical Computing, Vienna, Austria). In total, 351 baclofen users and 1241 eperisone users were identifed. Baclofen users with CKD had a signifcantly increased risk of respiratory depression (odds ratio, 8.03; 95% confdence interval, 1.88-34.19; P = .02); no increased risk of respiratory depression was observed in eperisone users with CKD (Table S1). In baclofen users, respiratory depression was signifcantly associated with only the presence of CKD (odds ratio, 7.51; 95% confdence interval, 1.47-38.40; P = .02; Table 1). To the author’s knowledge, this is the frst report to show increased risk of respiratory depression in ba- clofen users with CKD. Baclofen is eliminated mainly via the kidneys, and baclofen clearance is equal to cre- atinine clearance. 9 Therefore, baclofen users with CKD may have an increased risk of respiratory depression due to the increased serum concentration of baclofen. A limitation of this study is potential reporting bias in JADER, and the results showed increased frequencies of only certain factors. Respiratory depression is a rare adverse event; therefore, a clinical trial with a large sample size would be needed to assess the risk factors. In conclusion, health care providers should recognize that baclofen users with CKD are at risk for potential respiratory depression. Conficts of Interest The author declares no conficts of interest. Funding No external funding was received to conduct this study. Department of Pharmacy, Kaetsu Hospital, Niigata, Japan Submitted for publication 18 January 2021; accepted 19 February 2021. Corresponding Author: Satoru Mitsuboshi, PhD, 1459-1 Higashikanazawa, Akiha-ku, Niigata-shi, Niigata 956-0814, Japan Email: ccrtyo34057@gmail.com