Armodafinil for excessive daytime sleepiness : a systematic review of randomized controlled trials

Abstract

Excessive sleepiness is the most concerned and debilitating symptoms suffered by patients with various sleep disorders around the world. In recent years, the use of Armodafinil, the R-isomer of the racemic Modafinil, has become increasingly popular as the pharmacological agent for treating excessive sleepiness.

In this study, a systematic review on Armodafinil, being the first systematic review focusing on its clinical application on various sleep disorders, was conducted. Major electronic literature databases were systematically searched by two researchers independently, with relevant papers selected and data extracted. The methodological qualities of the included papers are further evaluated based on the Modified Jadad scoring system and Cochrane criteria for risk of bias. Eleven randomized controlled trials were included. Meta-analyses of Armodafinil against placebo were then performed on different extractable outcome parameters.

Our systematic review found that Armodafinil is consistently effective in treating excessive sleepiness and fatigue, as well as improving the general clinical conditions, related to various dyssomnias. These are confirmed by the meta-analysis on different outcome domains, namely subjective sleepiness measures (i.e. reduction in Epworth Sleepiness Score, -1.92, 95% CI [-2.72, -1.11], p<0.00001; heterogeneity I^2=0%), objective sleepiness measures (i.e. increase in mean sleep latency in Maintenance of Wakefulness Test, 2.97 min, 95% CI [1.88, 4.05], p<0.00001, heterogeneity I^2=34%; and Multiple Sleep Latency Test, 6.74 min, 95% CI [5.99, 7.49], p<0.00001, heterogeneity I2=0%, ), and other clinical markers (i.e. odds ratio of proportion with improved Clinical Global Impression of Changes, odds ratio 3.13; 95% CI [2.24, 4.38], p <0.00001; heterogeneity I^2=55%; reduction of fatigue level in Brief Fatigue Inventory, mean difference-0.77, 95% CI [-1.14, -0.41], p < 0.0001, heterogeneity I^2=39%). The important and significant implication of Armodafinil in the management of various sleep disorder and dyssomnia is therefore confirmed in this study.

Moreover, potential adverse effects with significant risk ratio are also revealed, including dry mouth (risk ratio 5.98, 95% CI [2.18, 16.44], p=0.0005), anxiety (risk ratio 4.83, 95% CI [2.41, 9.66], p<0.00001) and insomnia (risk ratio 4.47, 95 CI% [2.33, 8.58], p<0.0001). In general, Armodafinil is well tolerated by the patients with sleep disorders.