Effectiveness of Modafinil on Fatigue in Chronic Hepatitis C

Abstract

Introduction: Objective: To assess the efficacy of modafinil on fatigue in patients with Chronic Hepatitis C. Background: Hepatitis C Virus (HCV) is present in about 8% of the veteran population. Fatigue accompanies HCV infection in 53%-67% of patients and is sufficiently severe enough to impair activity in 17%. Modafinil is a unique wake-promoting agent that has been found to be effective in the treatment of fatigue in patients with multiple sclerosis. Methods: Patients aged 18-65 years with a diagnosis of HCV and mean score >27 on the fatigue severity scale (FSS) were eligible for the randomized double-blind placebo controlled trial. Exclusion criteria included hemoglobin <12, total bilirubin >2, uncontrolled diabetes with HBA1c >8, congestive heart failure with EF <35%, malignancy, or pregnancy. Patients received either placebo or 100 mg of modafinil for 2 weeks. Efficacy was evaluated with self-rating scales: fatigue severity scale (FSS) [score= 9-63], Epworth sleep scale (ESS) [score=0-24], and CES-D depression scale [score=0-60]. Change scores were calculated as pre-score minus post-score. Adverse events were also recorded. The independent samples t-test was used to compare groups on change scores. Results: Of the 25 patients enrolled, 4 were lost to follow-up. Eleven patients received modafinil and 10 received placebo. Ten patients in each group completed all outcome measures. No significant improvement in fatigue, sleep, or depression was demonstrated. FSS decreased 7.4 for the modafinil group (pre=50.2, post=42.8) vs. 6.4 for the placebo group (pre=48.9, post 42.5) [p=0.87]. ESS decreased 2.5 for the modafinil group (pre=12.3, post=9.8) vs. 0.8 for the placebo group (pre=10.9, post 10.1) [p=0.38]. CES-D decreased 5.35 for the modafinil group (pre=24.0, post=18.65) vs. 1.9 for the placebo group (pre=25.4, post 23.5) [p=0.36]. Serious adverse events were not found. The most common adverse events were headache and nausea. Conclusion: While 100 mg modafinil daily did not improve fatigue, sleep, or depression compared to placebo, our study was an exploratory study with limited power (n=10 for each group). We showed the feasibility of such a study (i.e., low dropout rate and no serious adverse events) and recommend a future investigation with a larger sample to determine the effectiveness of modafinil to reduce fatigue in HCV patients. The lack of improvement in fatigue in the modafinil group may have also been due to lower dose of modafinil used.