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      A review of sleep disorders and melatonin

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          Abstract

          Sleep disorders are a group of conditions that affect the ability to sleep well on a regular basis and cause significant impairments in social and occupational functions. Although currently approved medications are efficacious, they are far from satisfactory. Benzodiazepines, antidepressants, antihistamines and anxiolytics have the potential for dependence and addiction. Moreover, some of these medications can gradually impair cognition. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous hormone produced by the pineal gland and released exclusively at night. Exogenous melatonin supplementation is well tolerated and has no obvious short- or long-term adverse effects. Melatonin has been shown to synchronize the circadian rhythms, and improve the onset, duration and quality of sleep. It is centrally involved in anti-oxidation, circadian rhythmicity maintenance, sleep regulation and neuronal survival. This narrative review aims to provide a comprehensive overview of various therapeutic functions of melatonin in insomnia, sleep-related breathing disorders, hypersomnolence, circadian rhythm sleep-wake disorders and parasomnias. Melatonin offers an alternative treatment to the currently available pharmaceutical therapies for sleep disorders with significantly less side effects.

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          Most cited references39

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          REM sleep behavior disorder: Updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions.

          Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid, often frightening dreams associated with simple or complex motor behavior during REM sleep. The polysomnographic features of RBD include increased electromyographic tone +/- dream enactment behavior during REM sleep. Management with counseling and pharmacologic measures is usually straightforward and effective. In this review, the terminology, clinical and polysomnographic features, demographic and epidemiologic features, diagnostic criteria, differential diagnosis, and management strategies are discussed. Recent data on the suspected pathophysiologic mechanisms of RBD are also reviewed. The literature and our institutional experience on RBD are next discussed, with an emphasis on the RBD-neurodegenerative disease association and particularly the RBD-synucleinopathy association. Several issues relating to evolving concepts, controversies, and future directions are then reviewed, with an emphasis on idiopathic RBD representing an early feature of a neurodegenerative disease and particularly an evolving synucleinopathy. Planning for future therapies that impact patients with idiopathic RBD is reviewed in detail.
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            Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin.

            These practice parameters pertain to the treatment of hypersomnias of central origin. They serve as both an update of previous practice parameters for the therapy of narcolepsy and as the first practice parameters to address treatment of other hypersomnias of central origin. They are based on evidence analyzed in the accompanying review paper. The specific disorders addressed by these parameters are narcolepsy (with cataplexy, without cataplexy, due to medical condition and unspecified), idiopathic hypersomnia (with long sleep time and without long sleep time), recurrent hypersomnia and hypersomnia due to medical condition. Successful treatment of hypersomnia of central origin requires an accurate diagnosis, individual tailoring of therapy to produce the fullest possible return of normal function, and regular follow-up to monitor response to treatment. Modafinil, sodium oxybate, amphetamine, methamphetamine, dextroamphetamine, methylphenidate, and selegiline are effective treatments for excessive sleepiness associated with narcolepsy, while tricyclic antidepressants and fluoxetine are effective treatments for cataplexy, sleep paralysis, and hypnagogic hallucinations; but the quality of published clinical evidence supporting them varies. Scheduled naps can be beneficial to combat sleepiness in narcolepsy patients. Based on available evidence, modafinil is an effective therapy for sleepiness due to idiopathic hypersomnia, Parkinson's disease, myotonic dystrophy, and multiple sclerosis. Based on evidence and/or long history of use in the therapy of narcolepsy committee consensus was that modafinil, amphetamine, methamphetamine, dextroamphetamine, and methylphenidate are reasonable options for the therapy of hypersomnias of central origin.
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              Treatment outcomes in REM sleep behavior disorder.

              REM sleep behavior disorder (RBD) is usually characterized by potentially injurious dream enactment behaviors (DEB). RBD treatment aims to reduce DEBs and prevent injury, but outcomes require further elucidation. We surveyed RBD patients to describe longitudinal treatment outcomes with melatonin and clonazepam. We surveyed and reviewed records of consecutive RBD patients seen at Mayo Clinic between 2008-2010 to describe RBD-related injury frequency-severity as well as RBD visual analog scale (VAS) ratings, medication dosage, and side effects. Statistical analyses were performed with appropriate non-parametric matched pairs tests before and after treatment, and with comparative group analyses for continuous and categorical variables between treatment groups. The primary outcome variables were RBD VAS ratings and injury frequency. Forty-five (84.9%) of 53 respondent surveys were analyzed. Mean age was 65.8 years and 35 (77.8%) patients were men. Neurodegenerative disorders were seen in 24 (53%) patients and 25 (56%) received antidepressants. Twenty-five patients received melatonin, 18 received clonazepam, and two received both as initial treatment. Before treatment, 27 patients (60%) reported an RBD associated injury. Median dosages were melatonin 6 mg and clonazepam 0.5 mg. RBD VAS ratings were significantly improved following both treatments (p(m) = 0.0001, p(c) = 0.0005). Melatonin-treated patients reported significantly reduced injuries (p(m) = 0.001, p(c) = 0.06) and fewer adverse effects (p = 0.07). Mean durations of treatment were no different between groups (for clonazepam 53.9 ± 29.5 months, and for melatonin 27.4 ± 24 months, p = 0.13) and there were no differences in treatment retention, with 28% of melatonin and 22% of clonazepam-treated patients discontinuing treatment (p = 0.43). Melatonin and clonazepam were each reported to reduce RBD behaviors and injuries and appeared comparably effective in our naturalistic practice experience. Melatonin-treated patients reported less frequent adverse effects than those treated with clonazepam. More effective treatments that would eliminate injury potential and evidence-based treatment outcomes from prospective clinical trials for RBD are needed. Copyright © 2012 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Neurological Research
                Neurological Research
                Informa UK Limited
                0161-6412
                1743-1328
                June 03 2017
                May 01 2017
                June 03 2017
                : 39
                : 6
                : 559-565
                Affiliations
                [1 ] Department of Neurology, Beijing Haidian Hospital, Beijing, China
                [2 ] Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, MI, USA
                [3 ] Department of Neurology, Beijing Luhe Hospital Capital Medical University, Beijing, China
                Article
                10.1080/01616412.2017.1315864
                28460563
                46446844-53ab-45c7-beec-20a1022ea865
                © 2017

                http://creativecommons.org/licenses/by-nc-nd/4.0/

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