Safety profile of tasimelteon, a melatonin MT<sub>1</sub>and MT<sub>2</sub>receptor agonist: pooled safety analyses from six clinical studies

Léger, Damien; Quera-Salva, Maria-Antonia; Vecchierini, Marie-Françoise; Ogrizek, Pascale; Perry, Christina A; Dressman, Marlene A.

doi:10.1517/14740338.2015.1093112

Cited by 173 publications

(6 citation statements)

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“…Melatonin receptor agonists, such as Circadin® (prolonged-release MLT), ramelteon, agomelatine or tasimelteon, bind to and activate the MLT receptors 1 and 2 [ 42 ]. These analogues of MLT are believed to have the same mechanisms of action as MLT and are typically used for the treatment of sleep disorders and depression [ 43 ].…”

Section: Resultsmentioning

confidence: 99%

Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action

Posadzki

Bajpai

Kyaw

et al. 2018

BMC Med

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BackgroundOur aims were to evaluate critically the evidence from systematic reviews as well as narrative reviews of the effects of melatonin (MLT) on health and to identify the potential mechanisms of action involved.MethodsAn umbrella review of the evidence across systematic reviews and narrative reviews of endogenous and exogenous (supplementation) MLT was undertaken. The Oxman checklist for assessing the methodological quality of the included systematic reviews was utilised. The following databases were searched: MEDLINE, EMBASE, Web of Science, CENTRAL, PsycINFO and CINAHL. In addition, reference lists were screened. We included reviews of the effects of MLT on any type of health-related outcome measure.ResultsAltogether, 195 reviews met the inclusion criteria. Most were of low methodological quality (mean -4.5, standard deviation 6.7). Of those, 164 did not pool the data and were synthesised narratively (qualitatively) whereas the remaining 31 used meta-analytic techniques and were synthesised quantitatively. Seven meta-analyses were significant with P values less than 0.001 under the random-effects model. These pertained to sleep latency, pre-operative anxiety, prevention of agitation and risk of breast cancer.ConclusionsThere is an abundance of reviews evaluating the effects of exogenous and endogenous MLT on health. In general, MLT has been shown to be associated with a wide variety of health outcomes in clinically and methodologically heterogeneous populations. Many reviews stressed the need for more high-quality randomised clinical trials to reduce the existing uncertainties.Electronic supplementary materialThe online version of this article (10.1186/s12916-017-1000-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action

Posadzki

Bajpai

Kyaw

et al. 2018

BMC Med

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“…7,8 Preventive medications (verapamil and lithium are considered the primary options) present a number of contraindications and adverse events that may impede their use, while many cases prove refractory to the initial approach and require the administration of additional medications, warranting the investigation for additional candidates to enhance our armamentarium in the management of CH. 9 Exogenous melatonin (MT) constitutes a relatively safe treatment option 10,11 that has provided encouraging results in the prevention of PHDs including individuals with CH. 12 The response to exogenous MT, as well as the circadian pattern of CH episodes and the occurrence of nighttime headaches, 13 has fueled the hypothesis that biological timekeeping might be involved in the pathophysiology of CH.…”

Section: Introductionmentioning

confidence: 99%

Meta‐analysis of melatonin levels in cluster headache—Review of clinical implications

et al. 2020

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Cluster headache (CH) has been associated with circadian disturbances. The present systematic review examined available evidence for the utilization of melatonin (MT) in CH prophylaxis. First, case‐control studies assessing nocturnal MT or its urine‐expelled metabolite 6‐sulfatoxymelatonin (aMT6s) in CH individuals and healthy controls (HC) were reviewed and meta‐analyzed. Secondly, the results from randomized controlled trials (RCTs) and non‐randomized studies evaluating MT’s use in the prevention of CH were discussed. Literature search included MEDLINE, EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar, and OpenGrey. Bouts and remissions were assessed separately. Ten case‐control studies (adult participants) were retrieved. Seven evaluated serum MT; meta‐analysis involved only three of them (due to deficient reporting, n: bout = 31, remission = 38, HC = 31). Results were compatible with lower nocturnal serum MT levels during bouts [bout‐HC; FE‐MD = −29.89 pg/mL, 95% CI = (−46.00, −13.78), remission‐HC; FE‐MD = −2.40 pg/mL, 95% CI = (−16.57, 21.38), bout‐remission; RE‐MD = −32.10 pg/mL, 95% CI = (−56.78, −7.42)]. Nocturnal urinary melatonin was appraised in two studies, but reporting issues impeded the capitalization of the results. Nocturnal urine aMT6s was evaluated by two studies (n: bout = 29, remission = 22, HC = 20), and pooled results were indicative of lower aMT6s concentration in CH individuals during both active and inactive periods [bout‐HC; FE‐MD = −9.63 μg/nocturnal urine collection, 95% CI = (−14.40, −4.85), remission‐HC; FE‐MD = −9.12 μg/nocturnal urine collection, 95% CI = (−14.63,‐3.62), bout‐remission; FE‐MD = −0.58 μg/nocturnal urine collection, 95% CI = (−4.58, 3.42)]. Regarding CH prophylaxis, one RCT and two non‐randomized trials were retrieved, involving a total of 41 adult CH individuals (11—episodic, 31—chronic) and rendering the deduction of any conclusions precarious. Overall, available data for the role use of MT in CH are insufficient and inconclusive. Complementary studies evaluating endogenous MT concentrations and MT administration to patients with CH are warranted.

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“…Tasimelteon was shown to be well tolerated over the short term although headache (17 vs 7% with placebo), elevated liver enzymes (10 vs 5%), nightmares or abnormal dreams (10% vs none), upper respiratory tract (7% vs none), and urinary tract infections (7 vs 2%) were more common. Long-term tasimelteon administration seems safe and well tolerated: a pooled safety analysis of the six clinical trials by Leger et al ( 52 ) showed a total exposure of 258.64 patient years of use and similar discontinuation rates across tasimelteon and placebo.…”

Section: Melatonin Receptor Agonists: Tasimelteonmentioning

confidence: 99%

Non-24-Hour Sleep–Wake Rhythm Disorder in the Totally Blind: Diagnosis and Management

et al. 2017

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Several aspects of human physiology and behavior are dominated by 24-h circadian rhythms with key impacts on health and well-being. These include mainly the sleep–wake cycle, vigilance and performance patterns, and some hormone secretions. The rhythms are generated spontaneously by an internal “pacemaker,” the suprachiasmatic nuclei within the anterior hypothalamus. This master clock has, for most humans, an intrinsic rhythm slightly longer than 24 h. Daily retinal light exposure is necessary for the synchronization of the circadian rhythms with the external 24-h solar environment. This daily synchronization process generally poses no problems for sighted individuals except in the context of jetlag or working night shifts being conditions of circadian desynchrony. However, many blind subjects with no light perception had periodical circadian desynchrony, in the absence of light information to the master clock leading to poor circadian rhythm synchronization. Affected patients experience cyclical or periodic episodes of poor sleep and daytime dysfunction, severely interfering with social, academic, and professional life. The diagnosis of Non-24 Sleep–Wake Rhythm Disorder, also named free-running disorder, non-entrained disorder, or hypernycthemeral syndrome, remains challenging from a clinical point of view due to the cyclical symptoms and should be confirmed by measurements of circadian biomarkers such as urinary melatonin to demonstrate a circadian period outside the normal range. Management includes behavioral modification and melatonin. Tasimelteon, a novel melatonin receptor 1 and 2 agonist, has demonstrated its effectiveness and safety with an evening dose of 20 mg and is currently the only treatment approved by the FDA and the European Medicines Agency.

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Safety profile of tasimelteon, a melatonin MT₁and MT₂receptor agonist: pooled safety analyses from six clinical studies

Abstract: Long-term tasimelteon administration was safe and well-tolerated. This is supported by placebo-controlled data in both Non-24 and insomnia patients.

Cited by 173 publications

References 36 publications

Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action

Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action

Meta‐analysis of melatonin levels in cluster headache—Review of clinical implications

Non-24-Hour Sleep–Wake Rhythm Disorder in the Totally Blind: Diagnosis and Management

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Safety profile of tasimelteon, a melatonin MT1and MT2receptor agonist: pooled safety analyses from six clinical studies

Abstract: Long-term tasimelteon administration was safe and well-tolerated. This is supported by placebo-controlled data in both Non-24 and insomnia patients.

Cited by 173 publications

References 36 publications

Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action

Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action

Meta‐analysis of melatonin levels in cluster headache—Review of clinical implications

Non-24-Hour Sleep–Wake Rhythm Disorder in the Totally Blind: Diagnosis and Management

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Safety profile of tasimelteon, a melatonin MT₁and MT₂receptor agonist: pooled safety analyses from six clinical studies