Efficacy and Safety of Circadin® in the Treatment of Primary Insomnia

Efficacy and Safety of Circadin® in the Treatment of Primary Insomnia

Lemoine Patrick, Zisapel Nava

Nava Zisapel et al.

European Psychiatric Review 2008;1(1):40-3

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Circadin® (Neurim Pharmaceuticals) is a prolonged-release formulation of 2mg melatonin (PR-melatonin 2mg) that, when taken before bedtime, mimics the physiological pattern of melatonin excretion during the night. It was approved by the European Medicines Agency (EMEA) in June 2007 for the short-term treatment of primary insomnia characterized by poor quality of sleep in patients over 55 years of age. PR-melatonin 2mg is a first-class medicine that goes beyond the facilitation of sleep onset of other widely used drugs for insomnia. This is due to its ability to improve sleep quality, next-day alertness, and quality of life. No significant adverse events were found with PR-melatonin 2mg compared with placebo. It can be used concomitantly with most medications, but potentiates the hypnotic effects of gamma-aminobutyric acid (GABAA) receptor modulators. In contrast to traditional sedative hypnotics, it has shown no evidence of impairing cognitive or psychomotor skills, or of dependence or abuse potential.

Insomnia—Symptoms, Daytime Disturbances, and Treatment Options
Insomnia is the common complaint of difficulty initiating or maintaining sleep and/or experiencing poor quality of sleep (also termed non-restorative sleep, a subjective complaint about tiredness on waking and throughout the day, feeling rested and restored on waking, and the number of awakenings experienced during the night) over at least one month and with negative effects on subsequent daytime functioning.1–3 Patients may suffer immensely from a poor quality of sleep while their sleep quantity is within the normal limits.1,2 Insomnia is a very common disorder, and its prevalence increases with age4–7 and is 1.5 times higher in women than in men.8,9 The disorder may be primary, namely not attributable to any known physical or mental condition or environmental cause, or secondary, resulting from an existing physical or mental condition. The prevalence of poor sleep quality increases with age.10–12 Insomnia also has negative consequences on health-related quality of life.13–17 More so than poor sleep quantity, poor sleep quality corresponds negatively to physical and mental measures of health, wellbeing, activities of daily living, driving skills, memory, productivity, and satisfaction with life.10,11,18–23

The management of insomnia involves non-pharmacological and pharmacological approaches, and traditionally focuses on alleviating difficulties in initiating or maintaining sleep. The most commonly prescribed drugs for insomnia are benzodiazepines (e.g. temazepam) and non-benzodiazepine (e.g. zopiclone, zolpidem) hypnotics, which potentiate the central nervous system (CNS)-suppressant activity of brain GABAA receptors.24 None of these improve subsequent daytime functioning and they are all associated with a higher risk for driving accidents, falls and fractures, overdose, and cognitive impairment, along with the potential for abuse and dependence;25 therefore, their use is discouraged, particularly in elderly patients.26 An unmet medical need remains for a drug that improves quality of sleep. Thus, treatment focus has shifted to re-establishing restorative sleep, improving daytime functioning and quality of life, and avoiding withdrawal symptoms.26–28

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