Baclofen for the treatment of muscle cramps in patients with cirrhosis: A new alternative
Authors: Zachary H. Henry, Patrick G. Northup
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: Painful muscle cramps are a common complication of cirrhosis. Current therapies used in clinical practice mainly focus on vitamin repletion, electrolyte repletion, or altered energy metabolism with variable results, often leaving patients with no viable therapeutic options.1 Previous studies with quinidine and eperisone hydrochloride act on a proposed disruption of the nervous system leading to muscle cramps and showed moderate benefit, but have not been further assessed.2 Based upon these results and the potential interaction of the nervous system in the etiology of muscle cramps in patients with cirrhosis, we evaluated the antispasmodic medication, baclofen, for treatment of muscle cramps in patients with cirrhosis. Subjects with a diagnosis of cirrhosis and a complaint of muscle cramps were enrolled in a pilot study using low‐dose baclofen. Subjects underwent a muscle cramps questionnaire to identify frequency (days per week) and severity (1‐10 analog scale) of muscle cramps. All previous medications aimed at treating muscle cramps were held for the duration of the study. Subjects were then given baclofen 5 mg three times a day (TID) for 1 week, and, if tolerated, the dose was then increased to 10 mg TID. At the end of a 4‐week treatment period, the muscle cramps survey was repeated. Baclofen was tapered off, a 2‐week washout period was observed, and the muscle cramps survey was repeated. Side effects were assessed weekly throughout the study period by telephone. A total of 10 subjects underwent treatment with baclofen, with 8 subjects completing the treatment protocol. One subject dropped out of the study after 1 week because of somnolence, and 1 subject passed away secondary to complications of an incarcerated umbilical hernia. A third patient completed the treatment protocol, but underwent liver transplantation before completing the washout period. Rates of efficacy and common side effects are shown in Table 1. Routine blood tests were not performed during the study period, but 1 subject was diagnosed with hyponatremia during the study period by their primary hepatologist. This resolved without stopping baclofen and was not considered to be related to therapy. There were no reports from subjects or their primary hepatologists of drug‐induced liver injury. Three subjects were put back on baclofen by their primary hepatologist after the study period, ranging from 1 additional month of therapy to an additional year of therapy, with anecdotal reports of continued efficacy in treating their muscle cramps and no reported side effects leading to stopping baclofen. Table 1 - Efficacy and Side Effects Related to Baclofen Therapy Effectiveness Prestudy Period (mean ± SD) End of Study Period (mean ± SD) Washout Period (mean ± SD) P Valuea P Valueb Frequency (days per week) 5.5 ± 2.1 1.4 ± 2.0 4.6 ± 2.1 0.01 0.09 Severity (1‐10 analog scale) 8.5 ± 1.8 2.8 ± 2.7 7.1 ± 2.5 <0.01 0.04 Side Effect, % Prestudy Period End of Study Period Historic Rates5 P Valuea Headache 60 30 4‐8 0.08 Nausea 20 40 4‐12 0.16 Dizziness 20 20 5‐15 0.99 Hepatic encephalopathy 0 0 Very Rare 0.99 Somnolence 0 10 10‐63 — aRepresents the change in value between the prestudy period and the end of study period.bRepresents the change in value between the end of study period and the washout period. This is the first study to evaluate baclofen for the treatment of muscle cramps in cirrhosis. The safety profile of low‐dose baclofen noted in this study is similar to previous studies evaluating the use of baclofen in patients with cirrhosis.4 Baclofen is a readily available prescription medication that appears to be a safe, effective alternative for treament of muscle cramps in this patient population. Though larger, randomized, placebo‐controlled trial data are needed to verify the effect observed here, we believe that baclofen can serve as a reasonable alternative therapy for muscle cramps in patients with cirrhosis.