The efficacy of melatonin and melatonin agonists in insomnia – An umbrella review

Low, Tian Ling; Sum, Faith Nadine Choo Yun; Tan, Shian Ming

doi:10.1016/j.jpsychires.2019.10.022

Cited by 51 publications

(28 citation statements)

References 18 publications

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“…In Europe, it is the active component of a medicine, Circadin R , consisting of a pharmaceutical prolonged release preparation, prescribed for sleep disturbances, that contains 2 mg of melatonin (10). However, no melatonin-based medicine has been approved by the US Food and Drug Administration (FDA), which has instead approved a non-selective melatonin receptor agonist, ramelteon (sold as Rozerem R ) (11,12). It is accepted that melatonin provides benefits via its putative antioxidant action or via activation of specific melatonin receptors.…”

Section: Introductionmentioning

confidence: 99%

Specificity and nanomolar potency of melatonin on G-protein coupled melatonin MT1 and MT2 receptors expressed in HEK-293T human embryo kidney cells

Rivas‐Santisteban¹,

Reyes‐Resina²,

Raïch³

et al. 2019

Melatonin Res.

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This is a pre-registered study, i.e. a study whose hypotheses and experiments designed to address these hypotheses have been deposited in a database before starting the experiments. The study aims at assessing the Gs versus Gi coupling and the potency of melatonin in the human version of melatonin MT1 and MT2 G-protein-coupled receptors expressed in HEK-293T cells. The results show that these receptors are Gi but not Gs coupled. By using a standard procedure of modulation of 0.5 µM forskolin-induced cAMP levels, it was found that the potency on MT2 receptor-mediated actions is in the low nanomolar range, but the potency on MT1 receptor is in the high nanomolar range. The potency of melatonin to stimulate the MT2 receptor is similar to that of a selective agonist, N-[2-(2-methoxy-6H-isoindolo[2,1-a]indol-11-yl)ethyl]butanamide (IIK7). Overall, the data on the potency of melatonin on its receptors will provide a new look for melatonin research. It is important to consider this finding for appropriately addressing physiological or therapeutic effects based on melatonin potency. Thus, the low doses of melatonin used in the existing prolonged release preparations or in other supplements should be revisited.

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Section: Introductionmentioning

confidence: 99%

Specificity and nanomolar potency of melatonin on G-protein coupled melatonin MT1 and MT2 receptors expressed in HEK-293T human embryo kidney cells

Rivas‐Santisteban¹,

Reyes‐Resina²,

Raïch³

et al. 2019

Melatonin Res.

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“…Trouble falling asleep, like sleep quality, varied across the 7 days of the week and differed between weekdays and weekends, but only for those with PTSD. Falling asleep has been closely studied to identify behavioral and pharmacologic interventions to decrease sleep latency [33][34][35]. However, little is known about the neurobiology of falling asleep.…”

Section: Discussionmentioning

confidence: 99%

Daily variation in sleep characteristics in individuals with and without post traumatic stress disorder

et al. 2021

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Background Sleep disturbances are common in individuals with post traumatic stress disorder (PTSD). However, little is known about how daily variation in sleep characteristics is related to PTSD. This study examined the night-to-night and weekday versus weekend variation in sleep duration, sleep quality, trouble falling asleep, and difficulty staying asleep in individuals with and without PTSD. Methods Participants (N = 157; 80 with PTSD, 77 without PTSD) completed daily self-reports of their nighttime sleep characteristics for 15 consecutive days. Linear mixed models were used to examine the associations between the 7 days of the week and weekday versus weekend variation in sleep characteristics and PTSD. Results Individuals with PTSD reported shorter sleep duration, lower sleep quality, more trouble falling asleep, and more difficulty staying asleep than individuals without PTSD. The pattern of change across the week and between weekdays and weekends was different between those with and without PTSD for sleep quality and trouble falling asleep. Among those with PTSD, sleep duration, sleep quality, and trouble falling asleep differed across the 7 days of the week and showed differences between weekdays and weekends. For those without PTSD, only sleep duration differed across the 7 days of the week and showed differences between weekdays and weekends. Neither group showed 7 days of the week nor weekday versus weekend differences in difficulty staying asleep. Conclusions On average those with PTSD had shorter sleep duration, poorer sleep quality, and greater trouble falling and staying asleep. In particular, the day of week variation in sleep quality and trouble falling asleep specifically distinguishes those with PTSD from those without PTSD. Our findings suggest that clinical care might be improved by assessments of sleep patterns and disturbances across at least a week, including weekdays and weekends. Future studies should explore the mechanisms related to the patterns of sleep disturbance among those with PTSD.

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“…The knowledge of clinical use of melatonin is growing, with evidence supporting the prescription of exogenous melatonin for a few clinical situations. In the case of adult chronic insomnia, a few studies show modest benefits for sleep onset, sleep latency and total sleep time, although clinical significance is still questionable (101,102). For this recommendation, typical doses are in the range of 1-5 mg. Melatonin is also currently recommended as an adjuvant treatment of insomnia in children and adolescents, particularly in those with comorbid ADHD or autism (103).…”

Section: Do Exogenous Melatonin and Melatonin Agonists Have Therapeutic And/or Prophylactic Effects On Depression?mentioning

confidence: 99%

Melatonin and Depression: A Translational Perspective From Animal Models to Clinical Studies

et al. 2021

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Daily rhythm of melatonin synchronizes the body to the light/dark environmental cycle. Several hypotheses have been raised to understand the intersections between melatonin and depression, in which changes in rest-activity and sleep patterns are prominent. This review describes key experimental and clinical evidence that link melatonin with the etiopathology and symptomatology of depressive states, its role in the follow up of therapeutic response to antidepressants, as well as the clinical evidence of melatonin as MDD treatment. Melatonin, as an internal temporal cue contributing to circadian organization and best studied in the context of circadian misalignment, is also implicated in neuroplasticity. The monoaminergic systems that underly MDD and melatonin production overlap. In addition, the urinary metabolite 6-sulfatoxymelatonin (aMT6) has been proposed as biomarker for antidepressant responders, by revealing whether the blockage of noradrenaline uptake has taken place within 24 h from the first antidepressant dose. Even though animal models show benefits from melatonin supplementation on depressive-like behavior, clinical evidence is inconsistent vis-à-vis prophylactic or therapeutic benefits of melatonin or melatonin agonists in depression. We argue that the study of melatonin in MDD or other psychiatric disorders must take into account the specificities of melatonin as an integrating molecule, inextricably linked to entrainment, metabolism, immunity, neurotransmission, and cell homeostasis.

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The efficacy of melatonin and melatonin agonists in insomnia – An umbrella review

Cited by 51 publications

References 18 publications

Specificity and nanomolar potency of melatonin on G-protein coupled melatonin MT1 and MT2 receptors expressed in HEK-293T human embryo kidney cells

Specificity and nanomolar potency of melatonin on G-protein coupled melatonin MT1 and MT2 receptors expressed in HEK-293T human embryo kidney cells

Daily variation in sleep characteristics in individuals with and without post traumatic stress disorder

Melatonin and Depression: A Translational Perspective From Animal Models to Clinical Studies

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