Best timing to administer melatonin

The objective of this article is not to explore melatonin usage simply for sedation properties, but to explore using it to regulate sleep rhythm and hygiene. The theory is that taking it earlier will also help regulate the cycle for patients to fall asleep at a more “normal” time. Additionally, patients who are oppositional to bedtime, which is known as bedtime resistance, are typically more willing to go to bed following melatonin administration. Melatonin administration around 6 PMReference Corvese ⁵ is optimal to regulate sleep cycles of patients, and it can help with bedtime resistance.

In many hospitals, when melatonin administration is ordered, the default timing is 9 PM or 10 PM. Administration of medications at 6 PM (neither evening nor bedtime) is not typical. Hence, this would be an inconvenience for nurses, which is why hospitals are reluctant to change their policies. Although this change in timing poses an additional task for nurses, the default timing for melatonin administration may be changed in electronic medical records to optimize sleep for patients who face bedtime resistance.

The variety of melatonin forms and dosages poses difficulty for patients choosing what is best for them. It has been proven that low doses of melatonin are effective for treating insomnia in patients because they best mimic a normal circadian rhythm.Reference Corvese ⁵ Doses of 0.3 mg and 1 mg were observed to stimulate psychological levels like those in young adults during the night.Reference Corvese ⁵ A review of 16 studies conducted with adults over the age of 55 years concluded that higher doses of melatonin lead to higher levels in the body for a longer time, which leaves room for undesired effects such as daytime drowsiness. Those suffering from insomnia are unable to get the rest that they need. Moreover, with age progression, natural peak nocturnal melatonin concentrations decrease.Reference Salahub, Wu and Burry ⁶ Melatonin given around 6:00 PM proved to decrease sleep latency significantly in elderly patients.Reference Corvese ⁵ Although 6:00 PM seems relatively early to take melatonin, patients taking it during the early evening shift their sleep earlier, which increases the total amount of sleep time.Reference Salahub, Wu and Burry ⁶ This means that the time taken to fall asleep is reduced, providing additional hours of sleep formerly consumed by insomnia. For optimal results, aim to take melatonin roughly 3–4 hours before your desired sleep time. Therefore, if you aim to be asleep by 10 or 11 PM, taking it around 6 or 7 PM would align with this recommendation (GoodRx).

Dosing

Since melatonin is not approved by the FDA, there are no true maximum doses as there would be for an FDA-approved drug. Clinically, it has been used upwards of 20 mg but is typically prescribed in doses of 3 mg, 6 mg, 9 mg, and 12 mg (package insert). ⁷ There are not enough data to administer more than 12 mg while also titrating other psychoactive drugs.

Due to an absence of FDA regulation, the actual concentration of the drug compared to what is indicated on the package insert becomes closely scrutinized. A study of 31 melatonin supplements determined that the real concentration of melatonin varied between −83% and + 478% of its labeled concentration.Reference Savage, Zafar and Yohannan ⁸ This unreliability in melatonin concentrations makes dosing difficult, not to mention possibly affecting research studies. Additionally, melatonin’s bioavailability has a broad range of 1%–74% due to the dose and development of the specific supplement.Reference Savage, Zafar and Yohannan ⁸ Despite these hurdles, melatonin has proved to be an effective sleep aid. Common side effects of melatonin include headache and drowsiness (1 in 10 people, package insert). ⁷

Melatonin for delirium

Hospitalized patients face the risk of developing a major cognitive disorder known as delirium, characterized by conscious states of confusion and circadian rhythm disruptions.Reference You, Fan and Lei ⁹ Evidence shows that since chronic sleep deprivation is a major stressor for the body, it can lead to delirium, especially due to symptoms such as high blood pressure and increased levels of cortisol and proinflammatory cytokines.Reference Maldonado ¹⁰ Additionally, chronic sleep deprivation creates sleep debt, which can also be another causal factor of delirium.Reference Maldonado ¹⁰ This can be difficult to manage, as patients with symptoms tend to be uncooperative. Research has shown that melatonin can be an 9effective treatment for preventing delirium and potentially reducing the duration of delirium-related episodes. Urinary 6-sulfatoxymelatonin is the main metabolite of melatonin and was found to be lower in patients when they were in a phase of hyperactive delirium, whereas patients who had hypoactive delirium showed higher levels of 6-sulfatoxymelatonin.Reference Maldonado ¹⁰ Eighteen studies with a total of 2137 hospitalized patients concluded that melatonin did indeed contribute to the prevention of delirium due to the regulation of patients’ sleep patterns.Reference You, Fan and Lei ⁹

Ramelteon

Since melatonin is a dietary supplement, it is not approved by the FDA but is still the primary recommended drug for insomnia by the American Academy of Family Physicians.Reference Salahub, Wu and Burry ⁶ Additional medication that can be used to treat insomnia includes ramelteon, which, contrary to melatonin, is FDA-approved. Ramelteon is a melatonin receptor agonist, specifically for MT1 and MT2 receptors.Reference Pandi-Perumal, Spence and Verster ¹¹ Contrary to melatonin, ramelteon is absorbed by the body much quicker due to its high affinity for the melatonin receptors; hence, it is administered 30 minutes before bedtime. There is only one dose for ramelteon, which is 8 mg (package insert). ¹²

Conclusion and future directions

The best time to administer melatonin is around 6 PM (1–2 hours before bedtime). This should be the standard of care in all hospitals and nursing homes and at home. There should be a change in practice and hospital policies.