Products
Melatonin is commercially available in the form of sustained-release tablets (Circadin, Slenyto). It was approved as a prescription drug in the EU in 2007 and in many countries in 2009. Melatonin may also be included in magistral formulations. Slenyto was registered in many countries in 2019. In some countries – for example, the United States, Canada, and Germany – over-the-counter “dietary supplements” containing melatonin are available. However, in our view, melatonin should be classified as a drug.
Structure and properties
Melatonin (C13H16N2O2, Mr = 232.3 g/mol) is formed in the pinealocytes of the pineal gland from the amino acid tryptophan and from serotonin: Tryptophan Serotonin -Acetylserotonin Melatonin. Chemically, it is -acetyl-5-methoxytryptamine and an indoleamine. Melatonin is a developmentally ancient molecule found not only in animals, but also in bacteria, algae, and plants.
Effects
Melatonin (ATC N05CH01) has sleep-promoting, sleep-modulating, and potent antioxidant properties and reduces body temperature. It is a natural hormone produced by the pineal (pineal) gland in the brain. Melatonin plays a central role in controlling the circadian rhythm and synchronizing the internal clock with the day-night cycle. It has several other functions in metabolism. Hormone release is dependent on light and is regulated by the suprachiasmatic nucleus (SCN), the human “internal clock” in the hypothalamus. Light is the main natural antagonist of the “darkness hormone”. Melatonin interacts with the internal clock and can reset it. Melatonin levels rise after nightfall and reach their maximum around the middle of the night. Subsequently, they slowly fall again. The effects are based on binding to MT1 and MT2 receptors. Melatonin is also a powerful antioxidant. Clinical studies have shown that melatonin is effective against the symptoms of jet lag. The effect is greater when traveling east and crossing multiple time zones.
Indications and indications for use
- For the short-term treatment of primary insomnia characterized by poor sleep quality in patients 55 years of age and older.
- Sleep disturbances (lnsomnia) in children and adolescents aged 2 to 18 years with autism spectrum disorder (ASD) and/or Smith-Magenis syndrome, when sleep hygiene measures were inadequate.
Melatonin is not approved in many countries for the following indications:
- Jet lag
- Shift work
- Winter depression (seasonal affective disorder), depression see under agomelatine.
- Other circadian rhythm disorders.
Dosage
According to the professional information. In jet lag (no approval), the correct timing of intake is important. The recommended dose is 0.5 to 5 mg melatonin in the evening before bedtime for 2 to 5 days after arrival. Melatonin should not be taken in the morning or during the day because it will cause drowsiness.
Contraindications
- Hypersensitivity
The drug should be used with caution if the effects of drowsiness could pose a safety risk. Refer to the drug label for complete precautions.
Interactions
Melatonin is a substrate of CYP1A and CYP2C19, and corresponding interactions are possible, for example, with fluvoxamine, a potent CYP1A inhibitor. Other interactions have been described with alcohol and centrally depressant drugs.
Adverse effects
Melatonin may cause drowsiness and sleepiness. The most common possible adverse effects of taking Circadin include headache, nasopharyngitis, back pain, and joint pain.
