Treatment of isolated REM sleep behavior disorder using melatonin as a chronobiotic

Kunz, Dieter; Stotz, Sophia; Bes, Frédérik

doi:10.1111/jpi.12759

Cited by 23 publications

(31 citation statements)

References 54 publications

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“…In one study, six months of low-dose 2 mg melatonin supplementation taken at the same clock time (between 10–11 pm, personalized to the individual’s chronotype) resulted in a decrease in iRBD symptom severity over the first four weeks of treatment. This improvement was maintained over the follow-up period of 4.2 ± 3.1 years [ 94 ].…”

Section: Clinical Usesmentioning

confidence: 99%

Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

Minich

Henning²,

Darley

et al. 2022

Nutrients

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Melatonin has become a popular dietary supplement, most known as a chronobiotic, and for establishing healthy sleep. Research over the last decade into cancer, Alzheimer’s disease, multiple sclerosis, fertility, PCOS, and many other conditions, combined with the COVID-19 pandemic, has led to greater awareness of melatonin because of its ability to act as a potent antioxidant, immune-active agent, and mitochondrial regulator. There are distinct similarities between melatonin and vitamin D in the depth and breadth of their impact on health. Both act as hormones, affect multiple systems through their immune-modulating, anti-inflammatory functions, are found in the skin, and are responsive to sunlight and darkness. In fact, there may be similarities between the widespread concern about vitamin D deficiency as a “sunlight deficiency” and reduced melatonin secretion as a result of “darkness deficiency” from overexposure to artificial blue light. The trend toward greater use of melatonin supplements has resulted in concern about its safety, especially higher doses, long-term use, and application in certain populations (e.g., children). This review aims to evaluate the recent data on melatonin’s mechanisms, its clinical uses beyond sleep, safety concerns, and a thorough summary of therapeutic considerations concerning dietary supplementation, including the different formats available (animal, synthetic, and phytomelatonin), dosing, timing, contraindications, and nutrient combinations.

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Section: Clinical Usesmentioning

confidence: 99%

Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

Minich

Henning²,

Darley

et al. 2022

Nutrients

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“…Data from publications regarding the efficacy of the pineal hormone melatonin in RBD are summarized in Table 2 [21,27,[32][33][34][35][36][37][38][39][40][41][42][43]. Melatonin secretion has been reported as delayed by 2 h in patients with RBD [44].…”

Section: Melatonin and Its Analoguesmentioning

confidence: 99%

“…Together with clonazepam, melatonin is considered to be a first-line therapy for RBD. Most reports suggesting improvements of RBD with melatonin have been single case reports, open-label trials, or retrospective analyses of cohorts (therefore classifiable as level II or level III of evidence) [21,27,[32][33][34][35][36][37][38][39][40]43]. Only three studies were randomized clinical trials with level I of evidence and a quality rate >50%, one of them involving a short series of eight patients treated with 3 mg of melatonin at night who showed significant clinical and PSG improvement of RBD [37] and the other two involving 30 patients treated with 2-6 mg/day of prolonged release melatonin who both showed a lack of improvement of RBD [41,42].…”

Section: Melatonin and Its Analoguesmentioning

confidence: 99%

Current Treatment Options for REM Sleep Behaviour Disorder

Jiménez‐Jiménez

Alonso‐Navarro

García‐Martín

et al. 2021

JPM

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The symptomatic treatment of REM sleep behaviour disorder (RBD) is very important to prevent sleep-related falls and/or injuries. Though clonazepam and melatonin are usually considered the first-line symptomatic therapy for RBD, their efficiency has not been proven by randomized clinical trials. The role of dopamine agonists in improving RBD symptoms is controversial, and rivastigmine, memantine, 5-hydroxytryptophan, and the herbal medicine yokukansan have shown some degree of efficacy in short- and medium-term randomized clinical trials involving a low number of patients. The development of potential preventive therapies against the phenoconversion of isolated RBD to synucleinopathies should be another important aim of RBD therapy. The design of long-term, multicentre, randomized, placebo-controlled clinical trials involving a large number of patients diagnosed with isolated RBD with polysomnographic confirmation, directed towards both symptomatic and preventive therapy for RBD, is warranted.

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“…REM sleep is a highly complex behavioural state. Not surprisingly, the influence of anticholinergic, serotonergic, noradrenergic and dopaminergic antidepressants on muscle tone in RBD is complex, as well 19 40 41. Antidepressants are known to trigger secondary RBD and to increase RWA in patients with iRBD 40.…”

Section: Discussionmentioning

confidence: 99%

Prognostic biomarkers in prodromal α-synucleinopathies: DAT binding and REM sleep without atonia

Kunz

Stotz

Zeeuw

et al. 2023

J Neurol Neurosurg Psychiatry

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BackgroundIsolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a prodromal state of clinical α-synucleinopathies such as Parkinson’s disease and Lewy body dementia. The lead-time until conversion is unknown. The most reliable marker of progression is reduced striatal dopamine transporter (DAT) binding, but low availability of imaging facilities limits general use. Our prospective observational study aimed to relate metrics of REM sleep without atonia (RWA)—a hallmark of RBD—to DAT-binding ratios in a large, homogeneous sample of patients with RBD to explore the utility of RWA as a marker of progression in prodromal α-synucleinopathies.MethodsDAT single-photon emission CT (SPECT) and video polysomnography (vPSG) were performed in 221 consecutive patients with clinically suspected RBD.ResultsvPSG confirmed RBD in 176 patients (162 iRBD, 14 phenoconverted, 45 non-synucleinopathies). Specific DAT-binding ratios differed significantly between groups, but showed considerable overlap. Most RWA metrics correlated significantly with DAT-SPECT ratios (eg, Montreal tonic vs most-affected-region: r=−0.525; p<0.001). In patients taking serotonergic/noradrenergic antidepressants or dopaminergic substances or with recent alcohol abuse, correlations were weaker, suggesting a confounding influence, unlike other possible confounders such as beta-blocker use or comorbid sleep apnoea.ConclusionsIn this large single-centre prospective observational study, we found evidence that DAT-binding ratios in patients with iRBD can be used to describe a continuum in the neurodegenerative process. Overlap with non-synucleinopathies and clinical α-synucleinopathies, however, precludes the use of DAT-binding ratios as a precise diagnostic marker. The parallel course of RWA metrics and DAT-binding ratios suggests in addition to existing data that RWA, part of the routine diagnostic workup in these patients, may represent a marker of progression. Based on our findings, we suggest ranges of RWA values to estimate whether patients are in an early, medium or advanced state within the prodromal phase of α-synucleinopathies, providing them with important information about time until possible conversion.

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Treatment of isolated REM sleep behavior disorder using melatonin as a chronobiotic

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 23 publications

References 54 publications

Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

Current Treatment Options for REM Sleep Behaviour Disorder

Prognostic biomarkers in prodromal α-synucleinopathies: DAT binding and REM sleep without atonia

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