Role of Melatonin in Sleep

Circadin.com May 24, 2016

Insomnia is the most common sleep disorder, occurring in 30 – 45% of adults. It is 1.5 times more likely to occur in women than in men1.

Insomnia is the perception or complaint of inadequate sleep due to difficulty falling asleep, waking up frequently during night, waking up early, or of non-refreshing or poor Quality of Sleep. All are associated with daytime distress or poor daytime functioning2.

Clinical data shows that poor Quality of Sleep corresponds negatively to measures of health, well-being and satisfaction with life more so than quantity of sleep1.

It is estimated that primary insomnia (defined as insomnia with no underlying conditions as its cause) affects 1-10% of the general population, increasing to up to 25% in the elderly1.

Key elements for the definition of primary insomnia include difficulties in initiating or maintaining sleep and/or non-restorative sleep (inadequate sleep quality) as well as negative effects on subsequent daytime functioning as a result of a poor Quality of Sleep3.

It is not surprising that the disruption of normal sleep patterns has an influence on a patient’s life. Insomnia has a statistically significant negative impact on daily functioning, alertness and responsiveness and Quality of Life4.

Studies have shown that patients with insomnia have impaired cognitive function, with slower reaction time, worse balance and poorer memory than control patients5 6. These difficulties are of prime concern in older adults, who may already experience some decline in cognitive function due to natural ageing7.

Melatonin – A signal of darkness and marker for circadian rhythms
Melatonin is a naturally occurring hormone that is key to sleep and the sleep-wake cycle in humans and animals8. In the body, melatonin is produced by the pineal gland in the brain when night falls. The retina detects failing light, and the level of melatonin gradually increases, reaching its peak in the middle of the night in natural circumstances9.

Our circadian rhythm (or ‘body clock’) is influenced by melatonin, as it acts as a ‘time cue’, anticipating sleep. It is also an important physiological regulator of the sleep-wake cycle8.

Melatonin is not a sedative, but a sign of darkness or night-time, and is a cue for innate night-time behaviour. In the morning when plasma levels of melatonin decrease, sleep ends and wakefulness begins8.

In humans, melatonin induces heat loss, reduces arousal and related brain activity and delays production of cortisol, which increases blood pressure and blood sugar, in preparation for sleep1.

The rise in prevalence of sleep disorders associated with age is concomitant with the decrease in melatonin levels that occur with age12.

Fig. 1

About Circadin®

Circadin® is a novel, first in class prolonged-release melatonin tablet formulation, which releases melatonin and mimics the physiological pattern of melatonin secretion.

Mode of Action

Because of its novel formulation, Circadin® releases melatonin gradually over 8-10 hours thereby mimicking the body’s natural release of melatonin and resulting in the re-setting of natural circadian rhythms and the encouragement of natural, restorative sleep13.

Circadin® has been demonstrated to preserve the natural sleep architecture. In Fig 2, the dark line (baseline) represents natural deep sleep which is maintained by Circadin®, in contrast to the hypnotic, zolpidem13.

Fig. 2

Circadin® is different from ordinary preparations of melatonin and is the first melatonin-containing prescription drug approved in the EU. It is also the first drug active on melatonin receptors to be licensed in the EU. Without the prolonged-release matrix formulation, melatonin levels would peak to much higher levels than needed and then rapidly fall due to short half-life (40-50 minutes) of melatonin, and this would provide too high levels at the beginning of the night and will not provide sufficient levels of melatonin throughout the sleeping period that mimic the natural profile and therefore would not reset the natural rhythms13.

Fig. 3 compares the melatonin concentration in blood plasma over time seen with Circadin® and immediate-release melatonin.

Fig. 3

Circadin® shortens sleep latency (time to get to sleep) but more importantly Circadin® has been shown to significantly improve sleep quality (see Fig 4) and morning alertness (the behavior following awakening). These are the pre-conditions for normal daily performance and productivity, leading to better Quality of Life14 15.

These features distinguish Circadin® from other available treatments. Circadin® is indeed the first sleep agent to demonstrate improvements in Quality of Life14 15.

Fig. 4

Safety and Tolerability

Unlike other sleep medications, Circadin® does not impair memory, daytime vigilance, or driving performance. Because Circadin® works via the natural sleep pathway, there are no rebound and withdrawal effects – the side effect profile is benign and there is no evidence of dependency15.

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