General Information

Q1: What is Circadin®?
A1: Circadin® 2 mg is a prolonged-release melatonin formulation, approved as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over(Ref. 1).

Q2: How does endogenous melatonin help me to sleep?
A2: Melatonin is a naturally occurring neuro-hormone mainly released in the evening and during the night.(Ref.1, Ref. 2, Ref. 3). Melatonin signals 'darkness', is associated with feeling sleepy, and regulates the sleep-wake cycle(Ref. 1, Ref. 2, Ref. 3, Ref. 4). Individual levels of melatonin vary, but it has been found that otherwise healthy people suffering from insomnia often have lower levels of melatonin than people without insomnia, and that melatonin therapy ameliorates the symptoms of insomnia(Ref. 5). Circadin® is prolonged-release melatonin, which adds exogenous melatonin to the endogenous melatonin throughout the night, thereby facilitating the feeling of sleepiness, the ability to fall asleep, and improving sleep quality and daytime functioning(Ref. 1).

Q3: What are the benefits to health care professionals in prescribing Circadin®?
A3: Untreated poor sleep carries a risk to the patient's health. Sleep difficulties are linked to, e.g., increased risk of fatigue, depression, anxiety, and physical morbidity(Ref. 6, Ref. 7) It is therefore important to treat insomnia. However, treatment is difficult due to the drawbacks with current hypnotics. Firstly, due to the fact that all available hypnotics have been developed and approved with the focus on their ability to improve poor sleep quantity, they rarely improve sleep quality and daytime functioning. Secondly, current hypnotics often cause serious side effects related to daytime functioning - memory impairment, cognitive deficits, falls and accidents(Ref. 8). On top of this, they carry a high risk of dependence and even abuse. This means that the risk-benefit ratio of current therapies is low, especially in the already vulnerable elderly population who are at increased risk of suffering from sleep problems(Ref. 8 ). Physicians are often reluctant to prescribe a hypnotic, and patients are equally reluctant to take it. By prescribing Circadin®, the physician will be able to offer the patient a safe and effective medication which improves the patient's quality of sleep, daytime functioning, time to fall asleep and quality of life - without the risk of withdrawal effects, rebound insomnia and amnesic effects, or the risk of dependence.

Q4: What are the most important benefits to patients?
A4: Untreated insomnia may lead to various health problems(Ref. 6, Ref. 7). Market research has shown that many people suffering from insomnia are reluctant to take sleep medications due to fear of dependency and side effects. Therefore, many patients, although suffering with the consequences of insomnia, e.g., fatigue, low daytime performance and even anxiety and depression, do not seek medical consultation but use various over-the-counter (OTC) and herbal remedies, and even alcohol, with limited efficacy at best(Ref. 9, Ref. 10) Circadin® improves quality of sleep and has clinically proven improvement on next-day alertness, a ´placebo like´ adverse event profile(Ref. 5), and no evidence of dependence.

Q5: Are there any new trials on the horizon?
A5: As a post-approval commitment, a study to confirm the lack of dependence, rebound and withdrawal effects will start shortly(Ref. 12). Further studies are under discussion.

---

References

1. Circadin® 2 mg prolonged-release tablets. Summary of product characteristics. 2008.

2. Pandi-Perumal SR, Srinivasan V, Spence DW, Cardinali DP. Role of the melatonin system in the control of sleep: therapeutic implications. CNS Drugs 2007; 21 (12): 995-1018.

3. Zisapel N. Circadian rhythm sleep disorders. Pathophysiology and potential approaches to management. CNS Drugs 2001; 15 (4): 311-328.

4. Reiter RJ. Normal patterns of melatonin levels in the pineal gland and body fluids of humans and experimental animals. J Neural Transm 1986; 21 (Suppl.): 35-54.

5. Leger D, Laudon M, Zisapel N. Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy. Am J Med 2004; 116 (2): 91-95.

6. Ohayon MM. Prevalence and correlates of nonrestorative sleep complaints. Arch Intern Med 2005; 165 (1): 35-41.

7. Pilcher JJ, Ginter DR, Sadowsky B. Sleep quality versus sleep quantity: relationships between sleep and measures of health, well-being and sleepiness in college students. J Psychosom Res 1997; 42 (6): 583-596.

8. Glass J, Lanctôt KL, Herrmann N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ 2005; 331 (7526): 1169.

9. Morin CM, LeBlanc M, Daley M, et al. Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Medicine 2006; 7: 123-130.

10. National Institute of Health. NIH State of the Science Conference statement on manifestations and management of chronic insomnia in adults statement. J Clin Sleep Med 2005; 1 (4): 412-421.

11. 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.

12. EPAR, Assessment Report for Circadin. Procedure No. EMEA/H/C/695. 2007.