1. Clinical Overview
Melatonin is a neurohormone primarily synthesized and secreted by the pineal gland in a circadian rhythm, with peak levels occurring during the night. The 5mg oral formulation is a synthetic version used pharmacologically to treat circadian rhythm sleep disorders by promoting sleep initiation and regulating the sleep-wake cycle. It acts as a chronobiotic (resets the body clock) and a mild hypnotic.
| Onset | Duration | Bioavailability |
|---|---|---|
| 30 to 60 minutes | 4 to 8 hours | Approximately 15% (range 10-56%) due to significant first-pass metabolism. |
2. Mechanism of Action
Melatonin exerts its primary effects by acting as an agonist at melatonin receptors (MT1 and MT2) in the suprachiasmatic nucleus (SCN) of the hypothalamus, the body's master circadian clock. Activation of MT1 receptors promotes sleepiness and inhibits neuronal firing in the SCN. Activation of MT2 receptors is involved in phase-shifting circadian rhythms, thereby synchronizing the sleep-wake cycle to the external environment (light-dark cycle). It also has free radical scavenging antioxidant properties.
3. Indications & Uses
- Primary Insomnia (characterized by difficulty with sleep initiation) in adults aged 55 years and over.
- Circadian Rhythm Sleep-Wake Disorders: Delayed Sleep-Wake Phase Disorder (DSWPD).
- Jet Lag Disorder (for alleviation of symptoms).
4. Dosage & Administration
Adult Dosage: For Insomnia (≥55 years): 2mg to 5mg, taken 1-2 hours before bedtime. For Circadian Rhythm Disorders: 0.5mg to 5mg, taken 2-4 hours before desired bedtime (timing is critical). For Jet Lag: 0.5mg to 5mg, taken at bedtime after arrival at destination for several days. Start with the lowest effective dose.
Administration: Take orally with or without food. However, taking on an empty stomach may lead to faster absorption. Take 1 to 2 hours before desired bedtime. Do not crush or chew sustained-release formulations (if available). Adhere strictly to timing for circadian rhythm applications.
5. Side Effects
Common side effects may include:
- Headache
- Drowsiness/sedation (next-day somnolence)
- Dizziness
- Nausea
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Fluvoxamine and other CYP1A2 inhibitors | Markedly increases melatonin plasma levels (by up to 17-fold), increasing risk of sedation and side effects. | Major |
| Cimetidine | Increases melatonin levels by inhibiting CYP1A2 and CYP2C19. | Moderate |
| CYP1A2 inducers (e.g., Smoking, Carbamazepine, Rifampicin) | Decrease melatonin plasma levels, potentially reducing efficacy. | Moderate |
| Central Nervous System (CNS) Depressants (e.g., Benzodiazepines, Zolpidem, Alcohol, Antipsychotics, Antihistamines) | Additive sedative effect, increasing risk of excessive drowsiness and impaired psychomotor performance. | Major |
| Anticoagulants/Antiplatelets (e.g., Warfarin) | Melatonin may increase INR and risk of bleeding; monitor INR closely. | Moderate |
| Antihypertensives (e.g., Nifedipine, Propranolol) | Melatonin may potentiate hypotensive effect; beta-blockers also inhibit endogenous melatonin production. | Moderate |
| Immunosuppressants (e.g., Cyclosporine, Tacrolimus) | Melatonin may stimulate immune function, potentially counteracting immunosuppressive therapy. | Moderate |
| Oral Contraceptives (Estrogens) | May inhibit melatonin metabolism, increasing its levels. | Moderate |
| Caffeine | May antagonize the sleep-promoting effects of melatonin. | Minor |
7. Patient Counselling
- DO take the tablet 1-2 hours before your planned bedtime.
- DO use it to establish a consistent sleep routine alongside good sleep hygiene.
- DO inform your doctor about all other medications and supplements you are taking.
- DONT take it just before an activity requiring alertness like driving.
- DONT crush or chew the tablet unless instructed (for immediate-release only).
- DONT consume alcohol while on this medication.
- DONT use it for long-term without medical supervision.
8. Toxicology & Storage
Overdose: Symptoms are an extension of pharmacological effects: Severe drowsiness, confusion, disorientation, ataxia, prolonged sleep, headache, vomiting. No reports of fatal overdose in humans.
Storage: Store at room temperature (15°C to 30°C), protected from light and moisture. Keep in the original container. Keep out of reach of children.