Prolonged-release melatonin for the treatment of insomnia: targeting quality of sleep and morning alertness

Abstract

Prolonged-release (PR) melatonin (Circadin ® , Neurim Pharmaceuticals, Tel-Aviv, Israel) is a nonbenzodiazepine licensed to treat primary insomnia in patients aged 55 years and older. It exerts its effects by mimicking endogenous melatonin, a hormone which regulates sleep. PR-melatonin has been shown to be effective in improving quality of sleep and morning alertness. An oral dose of 2 mg once-daily for 3 weeks has generally been well tolerated, and does not cause ‘hangover’ effects or impair memory and psychomotor skills. Insomnia is a common sleep disorder, the diagnosis of which is based on a patient’s complaint of difficulty in initiating or maintaining sleep and/or sleep that is of inadequate quality (nonrestorative sleep). The sleep disturbance should have been present for at least 1 month and be associated with a negative impact on functioning the following day [1,2]. Insomnia occurs in 30–45% of adults [3,4] and is 1.5-times more likely in women than in men [5,6]. The prevalence of insomnia increases with age [7,8]. Insomnia may be secondary – particularly when associated with mental disorders or pain – or primary, that is not attributable to any physical or mental disorder or to any environmental cause. There are widely varying reports of the prevalence of primary insomnia in the general population from 1–10% and ranging up to 25% in the elderly [9,10]. Sleep disorders, including primary insomnia, place a tremendous burden on society due to their association with psychiatric disorders, their negative impact on quality of life, their association with falls and road traffic accidents and the reduced productivity and increased utilization of healthcare services by sufferers [10–16]. There is a poor correlation between the clinical complaints associated with insomnia and the findings at polysomnography that frequently fail to demonstrate any sleep-quality related cause for the problem [17–20]. However, the tenth revision of the International Classification of Diseases (ICD 10) acknowledges that ‘there are people who suffer immensely from the poor quality of their sleep, while sleep in quantity is judged subjectively, and/or objectively as within the normal limits’ [2]. Sleep quality is thus an important parameter of the clinical complaint of insomnia, with the diagnosis and the evaluation of treatment effects based solely on subjective assessments.