Role of Melatonin Receptors in Managing Sleep Disorders

Melatonin Receptor Biology and Function

Melatonin acts through two high-affinity G protein-coupled receptors, MT1 and MT2, which are involved in the maintenance of circadian rhythms underlying the normal sleep-wake cycle, according to the American Geriatrics Society 1

Melatonin receptor agonists are particularly effective for treating circadian rhythm sleep-wake disorders, including Delayed Sleep-Wake Phase Disorder (DSWPD) and Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), especially in blind individuals, as recommended by the American Academy of Sleep Medicine 2
Melatonin receptor agonists are also effective for treating Irregular Sleep-Wake Rhythm Disorder (ISWRD), as stated by the American Geriatrics Society 3, 4
For Irregular Sleep-Wake Disorder (ISWD), studies evaluating melatonin have shown inconsistent results, with one trial in patients with Alzheimer's disease showing no significant improvement with 2.5 mg melatonin, though a trend toward improvement was seen with 10 mg, according to the American Geriatrics Society 3, 5

Unlike benzodiazepines and other hypnotics, melatonin receptor agonists have not demonstrated significant effects indicative of potential for abuse or motor and cognitive impairment, as reported by the American Geriatrics Society 1, 6

Melatonin receptor agonists should be considered as part of a multicomponent approach to sleep disorders that includes light therapy, structured physical and social activity, and sleep hygiene practices, as recommended by the American Geriatrics Society 3, 4, 6, 7
Placebo-controlled randomized clinical trials are needed to further determine the efficacy and safety of melatonin receptor agonists, particularly in the treatment of ISWD in patients with dementia, as stated by the American Geriatrics Society 3, 5