melatonin

Melatonin is a natural hormone produced by the pineal gland in the brain and is also synthetically produced and marketed over-the-counter in the U.S. as a dietary supplement.

Melatonin regulates the sleep-wake cycle (circadian rhythm) and supplemental melatonin is used to improve nighttime sleep in people with insomnia. Melatonin is also used to improve sleep in people with shift work sleep disorder or jet lag, and as an adjunct treatment in many other conditions that are characterized by low melatonin levels.

Melatonin levels start rising in the evening with fading light and remain elevated through the dark hours of the night, promoting sleep. The levels drop in the morning, signaling the body for wakefulness, and stimulating the activity of hormones such as serotonin which raise our energy. The best-known function of melatonin is sleep regulation, however, melatonin also has many other functions including anticancer, antioxidant, anti-inflammatory, immunity boosting and neuroprotective activities.

Melatonin is not officially FDA-approved as a drug because it is sold as a dietary supplement, but melatonin is widely used and considered by the American Academy of Family Physicians (AAFP) as first-line therapy for the treatment of insomnia. Melatonin is available in the form of oral tablets and liquids, transdermal patches and rectal suppositories. Uses of melatonin include the following:

• Primary insomnia
• Age-related insomnia in elderly people
• Benzodiazepine withdrawal in elderly with insomnia
• Jet lag
• Alzheimer’s disease
• Chronic fatigue syndrome
• Nicotine withdrawal
• Winter depression
• Prevention of cluster headache
• Migraine headache
• Cancer, as an adjunct therapy
• Low platelet levels (thrombocytopenia) associated with chemotherapy
• Premedication for surgery to reduce anxiety
• Tardive dyskinesia, a drug-induced movement disorder

Melatonin has orphan designation and research is ongoing for its use in:

• Treatment of circadian rhythm sleep disorders in blind people without light perception
• Neonatal hypoxic ischemic encephalopathy, brain damage in newborn caused due to reduced blood flow and oxygen
• Smith-Magenis syndrome, a developmental disorder, in combination with a beta-blocker
• Acetaminophen overdose
• Short bowel syndrome
• Necrotizing enterocolitis, an intestinal inflammatory condition that causes tissue death
• Acute radiation syndrome
• Hepatocellular carcinoma, cancer of the liver cells
• Pancreatic cancer
• Heatstroke

• Do not use melatonin concurrently with immunosuppressant medications; melatonin stimulates the immune system
• Use melatonin with caution in the following conditions:
  • Autoimmune disorders
  • Impaired liver or kidney function
  • High blood pressure (hypertension)
  • Seizure disorder
  • Depression
• Use with caution in children and adults younger than 20 years; melatonin may cause puberty delays, irregular menstruation and precocious puberty upon discontinuation
• Long-term use of melatonin may inhibit reproductive hormones

Common side effects of melatonin include:

• Headaches
• Dizziness
• Drowsiness
• Nausea
• Abdominal cramps
• Disruption of circadian rhythm
• Daytime sleepiness the next day
• Daytime fatigue
• Irritability
• Transient depression
• Feeling of unease (dysphoria) in depressed persons

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

There is no established dosage for melatonin because it is sold as a dietary supplement and not regulated by the FDA.

Suggested dosage:

• 0.125 mg
• 0.3 mg
• 0.5 mg
• 2 mg controlled release
• 3 mg
• 5 mg
• 10-50 mg

Benzodiazepine Withdrawal in Elderly with Insomnia

• 2 mg controlled release taken orally at night for up to 6 months; taper dose over 6 weeks

Cancer, Adjunctive Therapy

• 10-50 mg taken orally daily

Cluster Headache, Prevention

• 10 mg taken orally at night

Migraine Headache

• 3 mg taken orally at night

Insomnia

• 3-5 mg taken orally at night

Difficulty Falling Asleep

• 5 mg taken orally 3-4 hours before sleep period x 4 weeks

Difficulty Maintaining Sleep

• Use controlled release formulation

Thrombocytopenia, Chemo-related

• 20 mg taken orally at night

Jet Lag

• 0.5-5 mg taken orally at night

Eastbound

• Preflight, early evening dose followed by bedtime dosing for 4 days

Westbound

• Treat at bedtime for 4 days when in the new time zone

Chronic Fatigue Syndrome

• 5 mg taken orally at night

Nicotine Withdrawal

• 0.3 mg taken orally 3.5 hours after stopping smoking

Winter Depression

• 0.125 mg taken orally twice daily

Premedication for Surgery

• 0.5 mg/kg sublingually, placed under the tongue to dissolve

Tardive Dyskinesia

• 10 mg controlled-release taken orally once/day

• There is no evidence of life-threatening reactions from overdose of melatonin.
• Melatonin overdose may cause drowsiness, headache, vomiting and changes in blood pressure.
• Melatonin effects are short-lived, lasting just about an hour. In case of overdose, wait for the drug to wear out; if symptoms persist, seek medical help or contact Poison Control.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Dutasteride has no known severe interactions with other drugs.
• Serious Interactions of melatonin include:
  • abametapir
  • calcium/magnesium/potassium/sodium oxybates
  • givosiran
  • sodium oxybate
• Melatonin has moderate interactions with at least 221 different drugs.
• Mild interactions of melatonin include:
  • acebutolol
  • atenolol
  • betaxolol
  • bisoprolol
  • carvedilol
  • eucalyptus
  • labetalol
  • metoprolol
  • propranolol
  • sage
  • sotalol
  • timolol

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There is insufficient information on the safety and efficacy of melatonin use during pregnancy and breastfeeding; avoid use

• Take melatonin exactly as instructed in the product label or as prescribed by your doctor
• Melatonin is marketed as a dietary supplement in the US and does not require extensive pre-marketing approval from the FDA. Commercially available formulations may vary in strengths and there may also be a discrepancy between the labeling and the actual ingredients and their amounts; exercise caution in choosing your product
• Do not drink alcohol when you take melatonin and do not take melatonin concurrently with other central nervous system depressants such as benzodiazepines
• If insomnia is not resolved, discontinue melatonin and seek medical help