title: Some implications of melatonin use in chronopharmacology of insomnia.
abstract: The last decade has witnessed the emergence of new chronopharmacological perspectives. In the case of sleep disorders, the accumulating evidence suggests that even a minor dysfunction in the biological clock can impact broadly upon body physiology causing increases in sleep onset latency, phase delays or advances in sleep initiation, frequent nocturnal awakenings, reduced sleep efficiency, delayed and shortened rapid eye movement sleep and increased periodic leg movements, among others. Thus, restoration of the adequate circadian pattern of proper sleep hygiene, targeted exposure to light and the use of chronobiotic drugs, such as melatonin, which affect the output phase of clock-controlled circadian rhythms, can help to recover the sleep-wake cycle. The optimization of drug effects and/or minimization of toxicity by timing medications with regard to biological rhythms is known as chronotherapeutics. While chronotherapeutical approaches have been particularly successful in the treatment of hypertension, allergies and some forms of cancer, a time-dependent pharmacological approach can be also effective when dealing with sleep disruptions like insomnia. A large proportion of patients under benzodiazepine (BZD)/Z drug treatment fail to achieve a complete and sustained recovery and are left with residual symptoms, like tolerance or dependency, that make relapse or recurrence more likely, and poorer quality of life a reality. Thus the chronic and extensive use of BZD/Z drugs has become a public health issue and has led to multiple campaigns to reduce both prescription and consumption of BZD/Z-drugs. This short review discusses available data on the efficacy of melatonin to reduce chronic BZD use in insomnia patients.
authors.affiliation: Department of Science and Technology, National University of Quilmes and CONICET, Argentina.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Golombek
authors.affiliation: Somnogen Canada Inc., Toronto, ON, Canada M6H 1C5.
authors.forename: Seithikurippu R
authors.initials: SR
authors.lastname: Pandi-Perumal
authors.affiliation: Centre for Addiction and Mental Health, University of Toronto, 100 Stokes St., Toronto, ON, Canada M6J 1H4.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Brown
authors.affiliation: BIOMED-UCA-CONICET and Department of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, 1107 Buenos Aires, Argentina. Electronic address: danielcardinali@uca.edu.ar.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Cardinali
mesh_terms: D000818:Animals; D055870:Drug Chronotherapy; D006801:Humans; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D014851:Wakefulness / Q000187:drug effects
chemical_list: D008550:Melatonin
keywords: Benzodiazepines; Chronobiotics; Chronopharmacology; Circadian rhythms; Insomnia; Melatonin