1. Clinical Overview
Melatonin is an endogenous neurohormone primarily secreted by the pineal gland in a circadian rhythm, with peak levels at night. In the Indian pharmaceutical context, it is available as a dietary supplement and as a prescription drug (Schedule H) for specific indications. It plays a crucial role in synchronizing the sleep-wake cycle (circadian rhythm) and possesses antioxidant and immunomodulatory properties.
| Onset | Duration | Bioavailability |
|---|---|---|
| 30 to 60 minutes after oral administration. | 4 to 8 hours, depending on formulation (immediate vs. controlled-release). | Approximately 15-30% due to significant first-pass metabolism. Sublingual forms may have higher bioavailability. |
2. Mechanism of Action
Melatonin's primary mechanism is the agonist activity at melatonin receptors (MT1 and MT2) in the suprachiasmatic nucleus (SCN) of the hypothalamus, the body's master circadian clock. Activation of these receptors phase-shifts the circadian rhythm, promoting sleep initiation and regulating the timing of the sleep-wake cycle. It also has a mild hypothermic effect which may facilitate sleep.
3. Indications & Uses
- Primary insomnia characterized by poor quality of sleep (in patients aged 55 years and above)
- Circadian rhythm sleep-wake disorders (Delayed Sleep-Wake Phase Disorder, Jet Lag Disorder, Shift Work Disorder)
4. Dosage & Administration
Adult Dosage: For insomnia (≥55 years): 2-5 mg, taken 1-2 hours before bedtime. For circadian disorders: 0.5-5 mg, timing is critical and should be guided by a physician. Typical starting dose is 1-2 mg.
Administration: Take orally with or without food. For sleep initiation, take 30-60 minutes before desired bedtime. For jet lag, take at bedtime (destination time) after eastward travel or upon awakening after westward travel. Do not crush or chew controlled-release tablets. Sublingual tablets should be allowed to dissolve under the tongue.
5. Side Effects
Common side effects may include:
- Daytime drowsiness/sedation
- Headache
- Dizziness
- Nausea
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Fluvoxamine | Markedly increases melatonin levels (potent CYP1A2 inhibitor), increasing risk of sedation. | Major |
| Other CYP1A2 inhibitors (Ciprofloxacin, Estrogens) | Increased melatonin exposure. | Moderate |
| CYP1A2 inducers (Carbamazepine, Rifampicin, Smoking) | Decreased melatonin exposure, reducing efficacy. | Moderate |
| Central Nervous System Depressants (Benzodiazepines, Z-drugs, Opioids, Alcohol) | Additive sedative effects, impairing cognitive and motor performance. | Major |
| Anticoagulants/Antiplatelets (Warfarin) | Melatonin may increase INR; monitor coagulation parameters. | Moderate |
| Antihypertensives (Nifedipine, Verapamil) | May potentiate hypotensive effect. | Moderate |
| Immunosuppressants (Cyclosporine, Tacrolimus) | Theoretical immunostimulatory effect of melatonin may reduce efficacy of immunosuppressants. | Moderate |
7. Patient Counselling
- DO take it 30-60 minutes before your intended bedtime.
- DO use it to reset your sleep schedule for jet lag as directed.
- DO inform your doctor about all other medicines and supplements you are taking.
- DONT take it with alcohol.
- DONT drive or operate heavy machinery after taking melatonin until you know how it affects you.
- DONT use it as a substitute for good sleep hygiene (regular schedule, dark room, avoiding screens).
- DONT crush or chew controlled-release tablets.
8. Toxicology & Storage
Overdose: Excessive drowsiness, confusion, disorientation, ataxia, severe headache, vomiting. Symptoms are generally extensions of its pharmacological effects.
Storage: Store in a cool, dry place, away from light and moisture. Keep at room temperature (15-30°C). Keep out of reach of children. Do not use after the expiry date printed on the packaging.