Melatonin Receptor Agonists
Circadin®
Circadin® is the first and only natural/physiological sleep drug in a new therapeutic class – melatonin receptor agonists – approved in the EU for the treatment of patients with primary insomnia who are aged 55 years or over. Circadin® is a new treatment paradigm that targets sleep quality rather than sleep quantity, restoring sleep, allowing for a better quality of life and daytime functioning, without any issues of dependency or rebound effects, and which is safe and effective for use in the fragile elderly population.'
Circadin® 2 mg is a sustained-release formulation of melatonin allowing for the release of melatonin over an extended period of time (8–10 hours).1 This ensures the maintenance of melatonin levels throughout the night by reproducing the natural endogenous melatonin cycle, and is one of the features that distinguishes Circadin® from immediate-release preparations of melatonin (Figure 1). Without the sustained-release matrix formulation, melatonin levels would peak and then rapidly fall due to the short half-life of melatonin, and this would not provide levels of melatonin throughout the sleeping period that mimic the natural profile.
Circadin® improves sleep quality
A significantly higher proportion of patients responded to Circadin®, as compared with placebo treatment, with regard to an improvement in the quality of sleep, assessed using LSEQ.
Circadin® improves morning alertness
A significantly higher proportion of patients responded to Circadin®, as compared with placebo treatment, with regard to an improvement in morning alertness (LSEQ-BFW).2
Circadin® maintains deep sleep
Power density spectral analysis of the EEG is used to study any changes in the architecture of specific sleep stages. Circadin® has demonstrated an ability to maintain deep sleep, according to the EEG power density at low frequencies (1–10 Hz).3 In contrast, BZDs and ‘z’-drugs show a decrease in EEG power density in the low frequency range, suggesting a reduction in deep sleep.
Circadin® significantly improves quality of life
Circadin® has been shown to significantly improve patient QOL compared with placebo, as assessed by the WHO-5 Well-being Index in the pivotal study, NEURIM IX (Figure 5).1 This indicates that the benefit of Circadin® in restoring sleep is actually perceived by the patient in terms of their daily well-being.
Circadin® has an extremely good safety profile, with no obvious differences in safety parameters between active treatment and placebo.4,2 Circadin® shows no dependency or withdrawal symptoms and there are no contraindications.2,5
Circadin® - patient selection and management
Circadin® is indicated as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over.
Administration of Circadin®: Oral use. Tablets should be swallowed whole
Dosage time: Recommended dose is 2 mg once daily, 1–2 hours before bedtime and after food. This dosage should be continued for three weeks for optimal effect.
- Works via the natural sleep pathway
- Provides the benefits of natural, restorative sleep
- Improves sleep quality
- Improves morning alertness
- No next-day impairment
- Improves Quality of Life
- Safe and non-addictive
Download the Circadin Summary of Product Characteristics
References:
1. Wade AG, Ford I, Crawford G, et al. Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin 2007; 23 (10): 2597–2605.
2. EPAR, Assessment Report for Circadin. Procedure No. EMEA/H/C/695. 2007.
3. Neurim Pharmaceuticals Ltd. Data on file.
4. Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res 2007; 16 (4): 372–380.
5. Circadin - Summary of Product Characteristics. Available at: http://www.emea.europa.eu (accessed July 2008)
6. Aldhous M, Franey C, Wright J, Arendt J. Plasma concentrations of melatonin in man following oral absorption of different preparations. Br J Clin Pharmacol 1985; 19 (4): 517–521.
7. Trachsel L, Dijk D-J, Brunner DP, et al. Effect of zopiclone and midazolam on sleep and EEG spectra in a phase-advanced sleep schedule. Neuropsychopharmacology 1990; 3 (1): 11–18.
8. Brunner DP, Dijk D-J, Münch M, Borbély AA. Effect of zolpidem on sleep and sleep EEG spectra in healthy young men. Psychopharmacology (Berl) 1991; 104 (1): 1–5.