Prolonged‐release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects

Abstract

SUMMARY Melatonin, secreted nocturnally by the pineal gland, is an endogenous sleep regulator.Impaired melatonin production and complaints on poor quality of sleep are common among the elderly. Non-restorative sleep (perceived poor quality of sleep) and subsequently poor daytime functioning are increasingly recognized as a leading syndrome in the diagnostic and therapeutic process of insomnia complaints. The effects of 3-weeks prolonged-release melatonin 2 mg (PR-melatonin) versus placebo treatment were assessed in a multi-center randomized placebo-controlled study in 170 primary insomnia outpatients aged ‡55 years. Improvements in quality of sleep (QOS) the night before and morning alertness (BFW) were assessed using the Leeds Sleep Evaluation Questionnaire and changes in sleep quality (QON) reported on five categorical unit scales. Rebound insomnia and withdrawal effects following discontinuation were also evaluated. PR-melatonin significantly improved QOS ()22.5 versus )16.5 mm, P = 0.047), QON (0.89 versus 0.46 units; P = 0.003) and BFW ()15.7 versus )6.8 mm; P = 0.002) compared with placebo. The improvements in QOS and BFW were strongly correlated (Rval = 0.77, P < 0.001) suggesting a beneficial treatment effect on the restorative value of sleep. These results were confirmed in a subgroup of patients with a greater symptom severity. There was no evidence of rebound insomnia or withdrawal effects following treatment discontinuation. The incidence of adverse events was low and most side-effects were judged to be of minor severity. PR-melatonin is the first drug shown to significantly improve quality of sleep and morning alertness in primary insomnia patients aged 55 years and older-suggesting more restorative sleep, and without withdrawal symptoms upon discontinuation.

Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models

“…Melatonin administration shifts circadian rhythms in both rodents [18] and humans [19] and improves sleep by shortening sleep latency and lengthening sleep duration [19] . Melatonin has been used successfully in treating insomnia [20] www.nature.com/aps Tian SW et al Acta Pharmacologica Sinica npg and various circadian rhythm disorders such as delayed sleep phase syndrome [21] and shift-work sleep disorder [22] . Melatonin and its agonists exert antidepressant-and/or anxiolytic effects in animal models [23][24][25][26][27][28][29][30][31][32][33][34] .…”

Dual- and Triple-Acting Agents for Treating Core and Co-morbid Symptoms of Major Depression: Novel Concepts, New Drugs

“…Although melatonin (which is released from the pineal gland and acts via MT 1 and MT 2 receptors in the SCN) does not exert marked antidepressant properties per se, it improves sleep and reschedules perturbed circadian rhythms in insomniacs. 81,[212][213][214] Such actions of agomelatine would be beneficial in depression, inasmuch as patients generally exhibit reduced sleep quality and are often desynchronized. 3,81,82 Reflecting melatoninergic agonist and 5-HT 2C receptor antagonist actions, agomelatine is effective in experimental models of antidepressant and anxiolytic properties.…”

Novos sedativos hipnóticos

“…No entanto, no caso da insônia crônica primária, os resultados ainda não são tão consistentes na questão manutenção do sono, exceto em populações específicas, como, por exemplo, em pacientes acima de 55 anos 25 . Segundo dados da literatura, a melatonina apresenta bom perfil de tolerabilidade e segurança, com poucos efeitos colaterais 23,25 .…”