Modafinil Improves Real Driving Performance in Patients with Hypersomnia: A Randomized Double-Blind Placebo-Controlled Crossover Clinical Trial

Philip, Pierre; Chaufton, C.; Taillard, Jacques; Capelli, Aurore; Coste, Olivier; Léger, Damien; Moore, Nicholas; Sagaspe, Patricia

doi:10.5665/sleep.3480

Cited by 93 publications

(50 citation statements)

References 22 publications

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“…At the time this study was initiated, there were no published randomized, controlled trials evaluating any wake promoting medication for idiopathic hypersomnia, although two trials of modafinil including idiopathic hypersomnia patients have recently been published. 10, 11 …”

Section: Introductionmentioning

confidence: 99%

Clarithromycin in γ‐aminobutyric acid–Related hypersomnolence: A randomized, crossover trial

Trotti¹,

Saini²,

Bliwise³

et al. 2015

Annals of Neurology

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Objective Some central hypersomnolence syndromes are associated with a positive allosteric modulator of GABA-A receptors in cerebrospinal fluid. Negative allosteric modulators of GABA-A receptors, including clarithromycin, have been reported to reduce sleepiness in these patients. We sought to systematically assess the effects of clarithromycin on objective vigilance and subjective sleepiness. Methods This was a five-week, randomized, placebo-controlled, double-blind, crossover trial of clarithromycin 500 mg with breakfast and lunch, in patients with hypersomnolence syndromes (excluding narcolepsy with cataplexy) and evidence for abnormal cerebrospinal fluid potentiation of GABA-A receptors. The study occurred at a university-affiliated medical center. The primary outcome measure was median reaction time on the psychomotor vigilance task (PVT) at week 2 in each condition. Secondary outcomes included the Epworth Sleepiness Scale, Stanford Sleepiness Scale, Functional Outcomes of Sleep, Pittsburgh Sleep Quality Index, the SF-36, and additional PVT measures. Results Twenty-three patients began treatment. Three patients dropped out, and final analyses were performed on twenty complete cases. Median reaction time was not significantly different between clarithromycin and placebo. Subjective measures of sleepiness were significantly improved on clarithromycin versus placebo. Altered taste perception occurred, but was the only side effect more common on clarithromycin than placebo. No serious adverse events occurred. Interpretation Subjective sleepiness, but not psychomotor vigilance, improved during a two-week course of clarithromycin. Although additional studies are needed, this suggests that clarithromycin may be a reasonable treatment option in patients with treatment-refractory hypersomnolence. This trial was registered at clinicaltrials.gov (NCT01146600) and supported by the American Sleep Medicine Foundation.

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Section: Introductionmentioning

confidence: 99%

Clarithromycin in γ‐aminobutyric acid–Related hypersomnolence: A randomized, crossover trial

Trotti¹,

Saini²,

Bliwise³

et al. 2015

Annals of Neurology

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“…For example, we have reported on the beneficial effect of blueenriched morning light administration to contain daytime sleepiness in a patient with cirrhosis. 40 Similarly, modafenil, a drug which improves driving performance in patients with narcolepsy and idiopathic hypersomnia, 41 has also been used to treat daytime sleepiness and fatigue in patients with primary biliary cirrhosis. 42 On the reverse side, an attempt at correcting night sleep disturbance with the histamine H1 blocker hydroxyzine in patients with cirrhosis and minimal HE was associated with some risk of precipitating severe HE.…”

Section: Implications Of the Interpretation Of Hepatic Encephalopathymentioning

confidence: 99%

Hepatic Encephalopathy and Sleepiness: An Interesting Connection?

Montagnese

Turco

Amodio

2015

Journal of Clinical and Experimental Hepatology

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Sleep-wake abnormalities in patients with cirrhosis have been traditionally associated with hepatic encephalopathy (HE). In recent years, a certain amount of work has been devoted to the study of this relationship. This has lead to a modified picture, with weakening of the association between HE and poor night sleep, and the emergence of stronger links between HE and excessive daytime sleepiness. This brief review focuses on the evidence in favor of the interpretation of HE as a sleepiness syndrome, and on the diagnostic, therapeutic and social implications of such an interpretation. ( J CLIN EXP HEPATOL 2015;5:S49-S53) S leepiness is the expression of a basic physiological need, not unlike hunger or thirst. 1 Its presence and its intensity can be indirectly measured by how readily sleep occurs, how easily it is disrupted, and how long it lasts. Sleep deprivation/restriction increase sleepiness, and sleep reverses it. Routine access to sleep, not unlike that to food or drink, is not only homeostatic, but is influenced by social and environmental factors. Thus subjective sleepiness and its indicators (yawning, nodding etc.) are reduced under conditions such as social interaction, exercise etc. 2 However, when sleepiness is severe, our ability to reduce its impact on behavior is reduced, and the likelihood of sleep increases. There is probably some degree of adaptation to chronic sleepiness, and successfully treated patients report that "they had forgotten the experience of complete alertness". 2 This could provide an explanation for our observation that induced hyperammonaemia results in significantly more pronounced subjective sleepiness in healthy volunteers compared to cirrhotic patients, who may be used to it. 3 The degree of daytime sleepiness is related to both the amount of nocturnal sleep (sleep deprivation/restriction results in increased sleepiness during the following day, 4 ) and its quality (night arousals of different etiology, fragmenting sleep, also result in increased daytime sleepiness. 5 ) Finally, there is a circadian element to sleepiness. Subjects who are allowed to nap in time-free environments do so in a biphasic pattern, with a nap in the middle of the 24-h cycle (or early in the afternoon). 6 Such rhythmicity is preserved in "jet-lagged" conditions, just like that of sleep and feeding.It is assumed that sleepiness is a central nervous system phenomenon with identifiable neural mechanisms. However, limited information is available on whether: 1) the neurochemistry of sleepiness is different to that of sleep; 2) sleepiness and alertness have common or separate neural and neurochemical correlates. The electroencephalogram (EEG) of behaviorally awake subjects who have been deprived/restricted of sleep documents microsleep episodes and increased amounts of theta activity. 7 These neurophysiological events are considered markers/correlates of sleepiness. Neurophysiological studies have implicated histamine, serotonin, catecholamines, and acetylcholine in the control of wakefulness, and gamm...

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“…The monotonous MWT condition allows a sensitive assessment of sleepiness within a shorter time period compared to a more active situation in a driving simulator or real driving. Nevertheless, the MWT is not only sensitive to treatment but can also predict driving performance fairly well [13,14]. In some countries (eg, France) the MWT is mandatory to assess fitness-to-drive in professional drivers with sleep-wake disorders.…”

Section: Introductionmentioning

confidence: 99%

Subjective perception of sleepiness in a driving simulator is different from that in the Maintenance of Wakefulness Test

2015

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Modafinil Improves Real Driving Performance in Patients with Hypersomnia: A Randomized Double-Blind Placebo-Controlled Crossover Clinical Trial

Abstract: Modafinil improves driving performance in patients with narcolepsy and idiopathic hypersomnia. The Maintenance of Wakefulness Test is a suitable clinical tool to assess fitness to drive in this population.

Cited by 93 publications

References 22 publications

Clarithromycin in γ‐aminobutyric acid–Related hypersomnolence: A randomized, crossover trial

Clarithromycin in γ‐aminobutyric acid–Related hypersomnolence: A randomized, crossover trial

Hepatic Encephalopathy and Sleepiness: An Interesting Connection?

Subjective perception of sleepiness in a driving simulator is different from that in the Maintenance of Wakefulness Test

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