Melatonin: A regulator of the sleep–wake rhythm

What it is

Melatonin is the hormone the pineal gland produces to mark the sleep–wake cycle. In Spain it is sold in two forms: as a food supplement, at doses below 2 mg, and as a prescription medicine (2 mg prolonged release) for insomnia in people over 55. It has proven efficacy in jet lag and circadian rhythm disorders, and a more modest effect in insomnia.

It does not cause dependence or tolerance like benzodiazepines. It is more useful for 'moving the clock' than as a sleeping pill: in severe chronic insomnia it adds little.

Mechanism of action

It regulates:

MT1 and MT2 receptors in the suprachiasmatic nucleus (the body clock)
It eases the transition from wakefulness to sleep
An antioxidant effect, with no proven clinical relevance

At the counter

When to recommend it

Transient insomnia (moving house, acute stress)
Jet lag
Shift workers (a circadian problem)
Insomnia in people over 55 (prescription presentation)

When not to

Allergy to melatonin or an excipient
Treatment with fluvoxamine (it sends levels soaring)
Pregnancy and breastfeeding (not enough data)
Liver failure

What to say at the counter. What changes the result most is the timing: about 30–60 minutes before going to bed, with the lights low. More dose does not mean more sleep: low doses are usually enough, and if after a few weeks it does not help, the insomnia deserves a consultation.

Warnings

Important Fluvoxamine: it inhibits CYP1A2 and multiplies melatonin levels. Avoid the combination.
Important Drowsiness: do not drive or operate machinery in the hours after taking it.
Caution Morning drowsiness if a large dose is taken, or taken very late.
Caution Alcohol and other sedatives add to the effect. In children, only on the paediatrician's advice.

Pharmacokinetics

Absorption: Variable oral absorption, with low bioavailability because of first-pass hepatic metabolism. Peak at 30–60 minutes (later for prolonged-release forms).
Distribution: Wide distribution. Moderate protein binding (about 60%).
Metabolism: Rapid hepatic metabolism via CYP1A2. It produces inactive metabolites.
Elimination: Renal elimination. Very short half-life (20–50 minutes), which is an advantage (no accumulation).

Melatonin vs lorazepam

Aspect	Melatonin	Lorazepam
Dependence	No	Yes
Tolerance	No	Yes
Potency in severe insomnia	Low	High
Mechanism	Circadian regulation	GABA (sedation)
Ideal indication	Circadian disorders	Short-term severe insomnia

Melatonin for circadian problems and transient insomnia. Lorazepam for severe insomnia, and only short term.

Self-assessment

Three questions. When you check your answers you will see the explanation for each one.

What is melatonin's main advantage over benzodiazepines? It is more potent It is cheaper No dependence, no tolerance: it works by restoring the natural rhythm
When should melatonin be taken for the best effect? On waking With a meal 30–60 minutes before going to bed, with the lights low
What dose of melatonin is usually enough? 5–10 mg (the more the better) 50 mg or more Low doses, around 0.5–2 mg

Training content. It does not replace the summary of product characteristics or clinical judgement.

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