Waking up to modafinil in shift work sleep disorder.

Sir,

Shift Work Sleep Disorder (SWSD) is a type of circadian rhythm sleep disorder resulting from a sleep-wake pattern that is dyssynchronous with one's internal biologic rhythm. If the imposed or voluntary shift in the timing of sleep exceeds the limits of circadian adaptation or if the cumulative sleep deprivation compounds, it results in a conglomeration of symptoms that characterize SWSD. Studies show that among rotating shift workers, 53% report falling asleep during the night shift at least once a week, in contrast to 23% of rotating workers on the day shift, and 8% of permanent day workers.[1] There is considerable morbidity from this disorder as exemplified by disasters like the Exxon-Valdez oil spill, Chernobyl nuclear power plant meltdown, the numerous accidents that occur at work place/during transport, and the loss of productivity from sick leaves. SWSD is found to have a negative impact on performance, quality of life, and health, with an increased risk for peptic ulcers and cardiovascular disease. It is also shown to reduce insulin sensitivity.

Advancing age and female gender tend to amplify the risk. Sleep logs/diaries, Morningness-Eveningness Questionnaire, Actigraphy (helps identify delayed or advanced sleep phase disorder, non-24-hour sleep syndrome and sleep disturbances in shift workers), polysomnography and phase markers like Core Body Temperature Rhythm, Melatonin Rhythm, etc, are important tools in the assessment of SWSD. Prescribed sleep/wake scheduling (planned napping, etc), circadian phase shifting, daylight/bright light exposure in the early morning (inhibits adaptive circadian phase resetting), timed melatonin administration, and promoting sleep with hypnotic medication have shown varying degrees of promise in the management of SWSD.[2]

Numerous studies have shown that promoting alertness with stimulant medications (analeptics) significantly improved night-time alertness in shift workers. Modafinil, [2-{(diphenylmethyl) sulfinyl}acetamide] and its derivatives (Adrafinil, a prodrug to modafinil and Armodafinil, (−R) enantiomer of racemic modafinil) are an important group in this class (FDA approved) and unlike methamphetamines, they have low abuse potential. Although the mechanism of action is not clear, modafinil is believed to increase the release of monoamines (catecholamines norepinephrine, and dopamine) from the synaptic terminals. The low abuse potential and the wakefulness-promoting effect is postulated to be mediated by the elevation of hypothalamic histamine levels and the difference in c-Fos activation distribution compared to amphetamines.[3] It has shown to reverse disruptions in cognitive performance and mood during the night shift. This has shown to improve measures of sleep latency, clinical-impression, rating, sustained-attention performance, enhancement of adaptive response inhibition and patient-estimated sleepiness.[4] Also, the morning-after sleepiness during commute was reduced and the subsequent sleep occurring 8-16 hours later is not hindered. In experimental models, Modafinil improved memory acquisition and reversed the long-term memory impairment induced by sleep deprivation.[5] Modafinil is also found to be of benefit in fatigue associated with HIV and multiple sclerosis, and has a potential role as an antiparkinsonian, neuroprotective agent and as an anti-relapse (to drug-seeking after abstinence) medication.

Modafinil certainly has a positive outcome when managing SWSD and it helps curb the associated morbidity, thereby increasing the all-round productivity.