Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial

Abstract

Aim. To compare the efficacy and safety of armodafinil, the R-enantiomer of modafinil, with modafinil in patients of shift work sleep disorder (SWSD). Material and Methods. This was a 12-week, randomized, comparative, double-blind, multicentric, parallel-group study in 211 patients of SWSD, receiving armodafinil (150 mg) or modafinil (200 mg) one hour prior to the night shift. Outcome Measures. Efficacy was assessed by change in stanford sleepiness score (SSS) by at least 2 grades (responder) and global assessment for efficacy. Safety was assessed by incidence of adverse events, change in laboratory parameters, ECG, and global assessment of tolerability. Results. Both modafinil and armodafinil significantly improved sleepiness mean grades as compared to baseline (). Responder rates with armodafinil (72.12%) and modafinil (74.29%) were comparable (). Adverse event incidences were comparable. Conclusion. Armodafinil was found to be safe and effective in the treatment of SWSD in Indian patients. The study did not demonstrate any difference in efficacy and safety of armodafinil 150 mg and modafinil 200 mg.

1. Introduction

A significant proportion of employed individuals in India work during night hours. This causes misalignment between the sleep and wake propensities that are controlled by hypothalamic circadian pacemaker [1] and results into shift work sleep disorder (SWSD). The reported incidence of SWSD in India is about 44.8% of night-shift workers and 35.8% of rotating workers [2]. SWSD is characterized by persistent excessive sleepiness during night work and insomnia when attempting sleep in the daytime [3]. Individuals with SWSD have significantly higher incidence of sleepiness-related accidents, absenteeism, depression, and missed family and social activities as compared with other night-shift workers [2]. It is also associated with higher incidence of ulcers, cardiovascular disease, and deficit in cognition and psychomotor performance [45].

The pharmacological management of SWSD involves treatment with modafinil that has been shown to improve wakefulness and ability to sustain attention in these patients. However, despite the half-life of 15 hours, the wakefulness promoting effect of modafinil is found to be ill-sustained in the last one third of night shift hours [6]. The lack of efficacy in the early morning hours and undue patient confidence in the drug can result into excessive sleepiness while commuting home. This can increase the chances of sleepiness-related accidents. Armodafinil, the chirally pure R-enantiomer of modafinil, approved by US FDA in 2007 has half-life (hours) three times longer than its S-enantiomer ( hours) [7]. Despite the same half lives, comparison of the equivalent (200 mg) doses of modafinil and armodafinil, in humans has revealed that armodafinil sustains higher plasma concentrations 6–14 hrs postadministration than that of racemic modafinil with longer maintenance of wakefulness [810].

This was a randomized, comparative, double-blind, and multicentric study comparing the effects of modafinil 200 mg with armodafinil 150 mg in Indian patients of SWSD. To our knowledge, this is the first comparative study in SWSD patients.

 

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