An open study of modafinil for the treatment of daytime somnolence and fatigue in primary biliary cirrhosis.
BACKGROUND
Fatigue is a debilitating symptom which frequently impairs the quality of life of patients with primary biliary cirrhosis (PBC). Although the mechanisms underpinning fatigue in PBC remain unclear, there is an emerging consensus that CNS mechanisms play a key role. It has recently been shown that there is a strong association between abnormalities in sleep regulation, in particular excessive daytime somnolence, and fatigue severity in PBC. The CNS-acting drug modafinil has an established role in the treatment of excessive daytime somnolence in non-liver disease states.


OBJECTIVE
To explore, in an open label study, the responses of PBC patients suffering from significant daytime somnolence and associated fatigue to modafinil therapy.


METHODS
All patients in the series (n = 21) underwent daytime somnolence assessment using the Epworth Sleepiness Scale and PBC symptom assessment using the PBC-40, a multi-domain, disease specific, psychometrically robust quality of life measure. Modafinil was started at a dose of 100 mg/day and was titrated according to tolerability and response. Patients underwent repeat Epworth Sleepiness Scale and PBC-40 assessment after 2 months of treatment.


RESULTS
Significant improvement was seen in Epworth Sleepiness Scale scores with modafinil therapy [15 +/- 3 vs. 8 +/- 6, P < 0.0005 (intention-to-treat analysis)]. An equally significant improvement in fatigue severity was also seen [PBC-40 fatigue domain score (46 +/- 6 vs. 34 +/- 12, P < 0.0001) (intention-to-treat analysis)].


CONCLUSIONS
Open label modafinil therapy was associated, where tolerated by patients, with improvement in excessive daytime somnolence and associated fatigue in PBC. Further study in placebo-controlled trials is warranted.
Jones
D E J
DE
Liver Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK. d.e.j.jones@ncl.ac.uk
Newton
J L
JL
D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D006970:Disorders of Excessive Somnolence / Q000188:drug therapy*; D005221:Fatigue / Q000209:etiology*; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000150:complications*; D008875:Middle Aged; D000077408:Modafinil; D012890:Sleep / Q000502:physiology
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil