Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian Rhythm Sleep‐Wake Disorders

Abstract

Circadian rhythm sleep‐wake disorders (CRSWDs) are characterized by persistent or recurrent patterns of sleep disturbance related primarily to alterations of the circadian rhythm system or the misalignment between the endogenous circadian rhythm and exogenous factors that affect the timing or duration of sleep. These disorders collectively represent a significant unmet medical need, with a total prevalence in the millions, a substantial negative impact on quality of life, and a lack of studied treatments for most of these disorders. Activation of the endogenous melatonin receptors appears to play an important role in setting the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Therefore, melatonin agonists, which may be able to shift and/or stabilize the circadian phase, have been identified as potential therapeutic candidates for the treatment of CRSWDs. Currently, only one melatonin receptor agonist, tasimelteon, is approved for the treatment of a CRSWD: non–24‐hour sleep‐wake disorder (or non‐24). However, three additional commercially available melatonin receptor agonists—agomelatine, prolonged‐release melatonin, and ramelteon—have been investigated for potential use for treatment of CRSWDs. Data indicate that these melatonin receptor agonists have distinct pharmacologic profiles that may help clarify their clinical use in CRSWDs. We review the pharmacokinetic and pharmacodynamic properties of these melatonin agonists and summarize their efficacy profiles when used for the treatment of CRSWDs. Further studies are needed to determine the therapeutic potential of these melatonin agonists for most CRSWDs.

Perspectives in affective disorders: Clocks and sleep

“…Not surprisingly, patented melatonin agonists (Tasimelteon ® and Ramelteon ® ) have been more stringently studied and approved for treating sleep disorders in the blind than melatonin itself. Agomelatine, which acts not only on melatonin receptors but also as a 5HT 2C antagonist, is available as an antidepressant (Williams, McLin, Dressman, & Neubauer, ).…”

Nicht-24-Stunden-Schlaf-Wach- Syndrom (Non-24)

“…Tasimelteon bindet stärker an den MT2-als an den MT1-Rezeptor, hat im Vergleich zu anderen Melatonin-Rezeptorantagonisten die stärkste Bindungsaffinität zu dem MT2-Rezeptor und besitzt eine kurze Halbwertszeit (54).…”

Common Sleep Disorders in Children

“…Sleep wake disorders have generally been managed in pediatrics with light therapy and melatonin (weak evidence); however, several melatonin receptor agonists are coming on to the market such as tasimelteon, ramelteon, and agomelatine, which all have distinct pharmacological profiles, none of which are yet approved for use in children and variably for use in adult insomnia. 58 It is important to realize that many medications used in pediatric medicine have an effect on sleep. These include SSRIs (reduction in REM sleep), benzodiazepines, and atypical antipsychotics (can affect SWS).…”