Melatonin (patient information)

# What is it?
- Melatonin is a hormone found naturally in the body. Melatonin used as medicine is usually made synthetically in a laboratory. It is most commonly available in pill form, but melatonin is also available in forms that can be placed in the cheek or under the tongue. This allows the melatonin to be absorbed directly into the body.
- People use melatonin to adjust the bodys internal clock. It is used for jet lag, for adjusting sleep-wake cycles in people whose daily work schedule changes (shift-work disorder), and for helping blind people establish a day and night cycle.
- Melatonin is also used for the inability to fall asleep (insomnia); delayed sleep phase syndrome (DSPS); insomnia associated with attention deficit-hyperactivity disorder (ADHD); insomnia due to certain high blood pressure medications called beta-blockers; and sleep problems in children with developmental disorders including autism, cerebral palsy, and intellectual disabilities. It is also used as a sleep aid after discontinuing the use of benzodiazepine drugs and to reduce the side effects of stopping smoking.
- Some people use melatonin for Alzheimers disease, ringing in the ears, depression, chronic fatigue syndrome (CFS), fibromyalgia, migraine and other headaches, irritable bowel syndrome (IBS), bone loss (osteoporosis), a movement disorder called tardive dyskinesia (TD), epilepsy, as an anti-aging agent, for menopause, and for birth control.
- Other uses include breast cancer, brain cancer, lung cancer, prostate cancer, head cancer, neck cancer, and gastrointestinal cancer. Melatonin is also used for some of the side effects of cancer treatment (chemotherapy) including weight loss, nerve pain, weakness, and a lowered number of clot-forming cells (thrombocytopenia).
- It is also used to calm people before they are given anesthesia for surgery.
- The forms of melatonin that can be absorbed through the cheek or under the tongue are used for insomnia, shift-work disorder, and to calm people before receiving anesthesia for surgery.
- Sometimes people apply melatonin to the skin to protect against sunburn.

# How effective is it?
- Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, Ineffective, and Insufficient Evidence to Rate.
- The effectiveness ratings for MELATONIN are as follows:
- Sleep disorders in blind people. Taking melatonin by mouth helps improve sleep disorders in blind children and adults.
- Trouble falling asleep (delayed sleep phase syndrome). Taking melatonin by mouth appears to reduce the length of time needed to fall asleep in young adults and children who have trouble falling asleep. However, within one year of stopping treatment, this sleeping problem seems to return.
- Sleeping problems in people with sleep-wake cycle disturbances. Taking melatonin by mouth is helpful for disturbed sleep-wake cycles in children and adolescents with intellectual disabilities, autism, and other central nervous system disorders. Melatonin also appears to shorten the time it takes for to children with developmental disabilities to fall asleep. In addition, melatonin appears to improve sleep quality in people with reduced rapid-eye movement (REM) sleep. Also, melatonin appears to reduce the time it takes to fall asleep and the number of sleep interruptions in elderly people with sleep-wake cycle disturbances and dementia.
- Possibly effective for
- Withdrawal from drugs called benzodiazepines. Taking the controlled-release form of melatonin by mouth seems to help older people with insomnia related to withrdrawal from drugs called benzodiazepines.
- High blood pressure. Taking the controlled-release form of melatonin before bedtime seems to lower blood pressure in people with high blood pressure.
- Insomnia. For primary insomnia (insomnia that is not attributable to a medical or environmental cause), melatonin seems to be able to shorten the amount of time it takes to fall asleep, but only by about 12 minutes, according to one research study. Melatonin does not appear to improve sleep efficiency, the percentage of time that a person actually spends sleeping during the time set aside for sleeping. Some people say melatonin makes them sleep better, even though tests do not agree. There is some evidence that melatonin is more likely to help older people than younger people or children. This may be because older people have less melatonin in their bodies to start with.
- There is some interest in finding out whether melatonin might help with secondary insomnia. This is trouble sleeping that is related to other conditions such as Alzheimers disease; depression; schizophrenia; hospitalization; and ICU syndrome, sleep disturbances in the intensive care unit. Research to date suggests that melatonin might not help to reduce the time it takes to fall asleep in secondary insomnia, but it might improve sleep efficiency.
- Jet lag. Most research shows that melatonin can improve certain symptoms of jet lag such as alertness and movement coordination. Melatonin also seems to slightly improve other jet lag symptoms such as daytime sleepiness and tiredness. However, melatonin might not be effective for shortening the time it takes for people with jet lag to fall asleep.
- Reducing anxiety before surgery. Melatonin used under the tongue seems to be as effective in reducing anxiety before surgery as midazolam, a conventional medication. It also seems to have fewer side effects in some people. Taking melatonin by mouth also seems to reduce anxiety before surgery, although some conflicting evidence exists.
- Tumors. Taking high doses of melatonin with chemotherapy or other cancer treatments might reduce tumor size and improve survival rates in people with tumors.
- Sunburn. Applying melatonin to the skin before sun exposure seems to prevent sunburn
- Low blood platelets (thrombocytopenia). Taking melatonin by mouth can improve low blood platelet counts associated with cancer, cancer treatment, and other disorders.
- Possibly ineffective for
- Exercise performance. Taking melatonin one hour before resistance exercise does not seem to improve performance.
- Infertility. Taking melatonin does not appear to improve fertility or pregnancy rates in women undergoing fertility treatments.
- Adjusting sleep schedule in people who do shift work. Taking melatonin by mouth does not seem to improve sleeping problems in people who do shift work.
- Likely ineffective for
- Depression. Although melatonin might improve sleeping problems in people with depression, it does not seem to improve depression itself. There is also some concern that melatonin might worsen symptoms in some people.
- Insufficient evidence to rate effectiveness for
- Age-related vision loss (age-related macular degeneration). Early research suggests that taking melatonin might delay the loss of vision in people with age-related vision loss.
- Memory loss (dementia). Some evidence suggests that taking melatonin does not improve behavior and symptoms in people with Alzheimers disease or other forms of dementia. However, other evidence suggests that taking melatonin might reduce confusion and restlessness in people with dementia
- Attention deficit-hyperactivity disorder (ADHD). Limited research suggests that melatonin might reduce insomnia in children with ADHD who are taking stimulants. However, improved sleep does not seem to decrease symptoms of ADHD.
- Enlarged prostate (benign prostatic hyperplasia). Some research suggests that taking melatonin can reduce excessive urination at night in some men with enlarged prostate.
- Insomnia caused by drugs called beta-blockers. There is early evidence that taking a melatonin supplement might decrease insomnia caused by drugs called beta-blockers.
- Bipolar disorder. Early research suggests that taking melatonin at bedtime increases sleep duration and reduces manic symptoms in people with bipolar disorder who also have insomnia.
- Chronic fatigue syndrome (CFS). Some early research suggests that taking melatonin in the evening might improve some symptoms of chronic fatigue syndrome, including fatigue, concentration, and motivation. However, other early research suggests that taking melatonin by mouth does not improve CFS symptoms.
- Lung disease (chronic obstructive pulmonary disease). Some evidence suggests that taking melatonin improves shortness of breath in people with COPD.
- However, it does not seem to improve lung function or exercise capacity.
- An inflammatory disease called chronic sarcoidosis. Early research suggests that taking melatonin daily improves lung function and skin lesions in people with chronic sarcoidosis.
- Cluster headache. Taking melatonin by mouth every evening might reduce the frequency of cluster headaches. However, other research suggests that it does not.
- Delirium. Some evidence suggests that taking melatonin nightly for 14 days reduces the risk of delirium in older people.
- Indigestion (dyspepsia). Taking melatonin nightly seems to reduce indigestion.
- Nighttime bedwetting (enuresis). Early research suggests that taking melatonin before bed does not reduce the number of wet beds in children with nighttime bedwetting.
- Fibromyalgia. Melatonin might decrease the severity of pain and stiffness in people with fibromyalgia.
- Acid reflux disease. Taking melatonin daily at bedtime might improve symptoms of acid reflux, including heartburn. However, taking conventional medication seems to be more effective.
- Stomach ulcers caused by H. pylori infection. Evidence suggests that taking melatonin together with the drug omeprazole improves healing in people with ulcers caused by H. pylori infection.
- Irritable bowel syndrome (IBS). Early research suggests that taking melatonin might improve some, but not all, symptoms of IBS.
- Menopausal symptoms. Limited research suggests that melatonin does not relieve menopausal symptoms. However, taking melatonin in combination with soy isoflavones might help psychological symptoms associated with menopause.
- Metabolic syndrome. Early research suggests that taking melatonin reduces blood pressure as well as low-density lipoprotein (LDL or bad) cholesterol in people with metabolic syndrome.
- Migraine headache. There is some evidence that taking melatonin before bed can prevent episodic migraine headache. When headaches do occur, they are milder and pass more quickly. However, other evidence shows that taking melatonin does not reduce the frequency of migraine attacks.
- Mild problems with mental function. Taking a docosahexaeonic acid (DHA) mixture that contains melatonin and tryptophan appears to improve mental function, speech, and sensitively to smell in older people with some problems with mental function.
- Withdrawal from nicotine. Taking melatonin 3.5 hours after nicotine withdrawal in smokers seems to reduce anxiety, restlessness, and cigarette cravings.
- Liver disease (nonalcoholic steatohepatitis). Some evidence suggests that taking melatonin improves liver function in people with nonalcoholic steatohepatitis.Recovery after surgery. Some evidence suggests that taking melatonin the night before and 1 hour before undergoing surgery might reduce pain and drug use after surgery.
- Prostate cancer. Taking melatonin by mouth together with conventional medications might reduce the growth of prostate cancer.
- Acting out dreams while sleeping. Some evidence suggests that taking melatonin before bed increases muscle paralysis during sleep in people with a sleep disorder that involves acting out dreams.
- Restless leg syndrome. Early research suggests that taking melatonin before bedtime might make symptoms worse in people with restless leg syndrome.
- Seizures. There is some evidence that taking melatonin at bedtime may reduce the number and length of seizures in children with epilepsy. However, other evidence suggests that it does not reduce seizures. Melatonin should be used cautiously, because melatonin may increase the number of seizures in some people.
- Headache characterized by sudden sharp pain. Some evidence suggests that taking melatonin daily might prevent sudden stabbing headaches.
- Stress. There is some evidence that taking melatonin might improve memory while under stress.
- Agitation caused by anesthesia drugs. Some evidence suggests that taking melatonin before anesthesia reduces agitation after surgery.
- Movement disorder (tardive dyskinesia). Some evidence suggests that taking melatonin by mouth decreases symptoms of a movement disorder called tardive dyskinesia. However, other evidence suggests that taking melatonin daily does not reduce involuntary movements.
- Ringing in the ears (tinnitus). Some evidence suggests that taking melatonin at night reduces ringing in the ears and improves sleep quality. However, other research suggests that it does not reduce ear ringing.
- Inflammatory bowel disease (ulcerative colitis). Taking melatonin daily in combination with conventional medication seems to help control a type of inflammatory bowel disease called ulcerative colitis.
- Osteoporosis.
- Birth control.
- Aging.
- Other conditions.
- More evidence is needed to rate melatonin for these uses.

# How does it work?
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- Melatonins main job in the body is to regulate night and day cycles or sleep-wake cycles. Darkness causes the body to produce more melatonin, which signals the body to prepare for sleep. Light decreases melatonin production and signals the body to prepare for being awake. Some people who have trouble sleeping have low levels of melatonin. It is thought that adding melatonin from supplements might help them sleep.

# Are there safety concerns?
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- Melatonin is LIKELY SAFE for most adults when taken by mouth short-term or when applied to the skin.
- Melatonin is POSSIBLY SAFE when used by mouth appropriately, long-term. Melatonin has been used safely for up to 2 years in some people. However, it can cause some side effects including headache, short-term feelings of depression, daytime sleepiness, dizziness, stomach cramps, and irritability. Do not drive or use machinery for four to five hours after taking melatonin.
- Special precautions & warnings:
- Pregnancy and breast-feeding: Melatonin is POSSIBLY UNSAFE to use during pregnancy. Do not use it. Melatonin might also interfere with ovulation, making it more difficult to become pregnant.
- Not enough is known about the safety of using melatonin when breast-feeding. It is best not to use it.
- Infants and children: Melatonin should not be used in most children. It is POSSIBLY UNSAFE. Because of its effects on other hormones, melatonin might interfere with development during adolescence.
- Bleeding disorders: Melatonin might make bleeding worse in people with bleeding disorders.
- High blood pressure: Melatonin can raise blood pressure in people who are taking certain medications to control blood pressure. Avoid using it.
- Diabetes: Melatonin might increase blood sugar in people with diabetes. Monitor your blood sugar carefully, if you have diabetes and take melatonin.
- Depression: Melatonin can make symptoms of depression worse.
- Seizure disorders: Using melatonin might increase the risk of having a seizure.
- Transplant recipients: Melatonin can increase immune function and might interfere with immunosuppressive therapy used by people receiving transplants.

# Are there interactions with medications?
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- Moderate
- Be cautious with this combination.
- Birth control pills (Contraceptive drugs)
- The body makes melatonin. Birth control pills seem to increase how much melatonin the body makes. Taking melatonin along with birth control pills might cause too much melatonin to be in the body.
- Some birth control pills include ethinyl estradiol and levonorgestrel (Triphasil), ethinyl estradiol and norethindrone (Ortho-Novum 1/35, Ortho-Novum 7/7/7), and others.

## Caffeine
- Caffeine might increase or decrease melatonin levels in the body. When taken together with melatonin supplements, caffeine seems to increase melatonin levels.

## Fluvoxamine (Luvox)
- Taking fluvoxamine (Luvox) can increase the amount of melatonin that the body absorbs. Taking melatonin along with fluvoxamine (Luvox) might increase the effects and side effects of melatonin.
- Medications changed by the liver (Cytochrome P450 1A2 (CYP1A2) substrates)
- Some medications are changed and broken down by the liver. Melatonin might decrease how quickly the liver breaks down some medications. Taking melatonin along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking melatonin, talk to your healthcare provider if you are taking any medications that are changed by the liver.
- Some medications changed by the liver include acetaminophen (Tylenol), amitriptyline (Elavil), clopidogrel (Plavix), clozapine (Clozaril), diazepam (Valium), estradiol, olanzapine (Zyprexa), ondansetron (Zofran), propranolol (Inderal), ropinirole (Requip), tacrine (Cognex), theophylline, verapamil (Calan, Covera-HS, Isoptin, Verelan), warfarin (Coumadin), and others.
- Medications changed by the liver (Cytochrome P450 2C19 (CYP2C19) substrates.
- Some medications are changed and broken down by the liver. Melatonin might decrease how quickly the liver breaks down some medications. Taking melatonin along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking melatonin, talk to your healthcare provider if you are taking any medications that are changed by the liver.
- Some medications changed by the liver include amitriptyline (Elavil), carisoprodol (Soma), citalopram (Celexa), diazepam (Valium), lansoprazole (Prevacid), omeprazole (Prilosec), phenytoin (Dilantin), warfarin, and many others.

## Medications for diabetes (Antidiabetes drugs)
- There is some concern that melatonin might increase or decrease blood sugar. Diabetes medications are used to lower blood sugar. By affecting blood sugar, melatonin might decrease or increase the effectiveness of diabetes medications. Monitor your blood sugar closely. The dose of your diabetes medication might need to be changed.
- Some medications used for diabetes include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), and others.

## Medications for high blood pressure (Antihypertensive drugs)
- Melatonin might decrease blood pressure in healthy people. However, melatonin might make blood pressure worse in people who are already taking medications for high blood pressure. Do not take too much melatonin if you are taking medications for high blood pressure.
- Some medications for high blood pressure include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.
- Medications that decrease the immune system (Immunosuppressants)
- Melatonin might increase the immune system. Taking melatonin along with medications that decrease the immune system might decrease the effectiveness of medications that decrease the immune system.
- Some medications that decrease the immune system include azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), daclizumab (Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), corticosteroids (glucocorticoids), and others.

## Medications that lower the seizure threshold
- Melatonin might increase the frequency of seizures in some people, particularly children. Taking melatonin with drugs that lower the seizure threshold might increase the risk of a seizure.
- Some medications that lower seizure threshold include anesthetics (propofol, others), antiarrhythmics (mexiletine), antibiotics (amphotericin, penicillin, cephalosporins, imipenem), antidepressants (bupropion, others), antihistamines (cyproheptadine, others), immunosuppressants (cyclosporine), narcotics (fentanyl, others), stimulants (methylphenidate), theophylline, and others.

## Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs)
- Melatonin might slow blood clotting. Taking melatonin along with medications that also slow clotting might increase the chances of bruising and bleeding.
- Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others like dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.

## Medications used to prevent seizures (Anticonvulsants)
- Melatonin might increase the frequency of seizures in some people, particularly children with multiple neurological disorders. In theory, taking melatonin might decrease the effectiveness of medications used to prevent seizures.
- Some medications used to prevent seizures include phenobarbital, primidone (Mysoline), valproic acid (Depakene), gabapentin (Neurontin), carbamazepine (Tegretol), phenytoin (Dilantin), and others.

## Methamphetamine
- Taking melatonin with methamphetamine might increase the effects and side effects of methamphetamine.

## Nifedipine GITS (Procardia XL)
- Nifedipine GITS (Procardia XL) is used to lower blood pressure. Taking melatonin might decrease the effectiveness of nifedipine GITS for lowering blood pressure.

## Sedative medications (Benzodiazepines)
- Melatonin might cause sleepiness and drowsiness. Drugs that cause sleepiness and drowsiness are called sedatives. Taking melatonin along with sedative medications might cause too much sleepiness.
- Some of these sedative medications include clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), and others.

## Sedative medications (CNS depressants)
- Melatonin might cause sleepiness and drowsiness. Medications that cause sleepiness are called sedatives. Taking melatonin along with sedative medications might cause too much sleepiness.
- Some sedative medications include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien), and others.

## Verapamil (Calan, Covera, Isoptin, Verelan)
- The body breaks down melatonin to get rid of it. Verapamil (Calan, Covera, Isoptin, Verelan) can increase how quickly the body gets rid of melatonin. Taking melatonin along with verapamil (Calan, Covera, Isoptin, Verelan) might decrease the effectiveness of melatonin.

## Minor
- Be watchful with this combination.

## Flumazenil (Romazicon)
(- Flumazenil (Romazicon) might decrease the effects of melatonin. It is not yet clear why this interaction occurs. Taking flumazenil (Romazicon) along with melatonin might decrease the effectiveness of melatonin supplements.

# Are there interactions with herbs and supplements?
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- CaffeineCaffeine might increase or decrease melatonin levels in the body. When taken together with melatonin supplements, caffeine seems to increase melatonin levels.
- EchinaceaTaking echinacea together with melatonin might have negative effects on immune function.
- Herbs and supplements that might lower blood pressureMelatonin might lower blood pressure. Using it along with other herbs and supplements that have this same effect might increase the risk of blood pressure dropping too low in some people. Some of these products include andrographis, casein peptides, cat's claw, coenzyme Q-10, fish oil, L-arginine, lycium, stinging nettle, theanine, and others.
- Herbs and supplements that might lower seizure thresholdMelatonin might increase the risk for seizures in some people, particularly in children. Taking supplements that also lower seizure threshold with melatonin might increase the risk even more. Some of these supplements include butanediol (BD), cedar leaf, Chinese club moss, EDTA, folic acid, gamma butyrolactone (GBL), gamma hydroxybutyrate (GHB), glutamine, huperzine A, hydrazine sulfate, hyssop oil, juniper, L-carnitine, rosemary, sage, wormwood, and others.
- Herbs and supplements that might slow blood clottingMelatonin might increase the effect of herbs that slow blood clotting and might increase the risk of bleeding in some people. These herbs include angelica, clove, danshen, garlic, ginger, ginkgo, Panax ginseng, red clover, willow, and others.
- Herbs and supplements with sleep-promoting (sedative) propertiesUsing melatonin along with herbs that have sedative properties might increase the effects and side effects of melatonin. Some of these supplements include 5-HTP, calamus, California poppy, catnip, hops, Jamaican dogwood, kava, St. John's wort, skullcap, valerian, yerba mansa, and others.
- St. John's wortTaking St. John's wort increases melatonin levels in the body. In theory, taking St. John's wort with melatonin might increase both the effects and side effects of melatonin.
- Vitamin B12Taking vitamin B12 might reduce blood levels of melatonin.
- Vitex agnus-castusTaking vitex agnus-castus increases melatonin levels in the body. In theory, taking vitex agnus-castus with melatonin might increase both the effects and side effects of melatonin.

# Are there interactions with foods?
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- There are no known interactions with foods.

# What dose is used?
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- The following doses have been studied in scientific research:
- BY MOUTH:
- For insomnia:
- 0.3-5 mg at bedtime is a typical dose.
- In children with insomnia due to delayed sleep onset, melatonin 5 mg at 6:00 PM daily.
- In children with developmental disorders (including cerebral palsy, autism, and intellectual disabilities), melatonin 5 mg at 8:00 PM daily. Both immediate-release and sustained-release preparations have been used.
- For jet lag: 0.5-5 mg at bedtime is commonly taken on the arrival day at the destination, continuing for 2-5 days. Low doses of 0.5-3 mg are often used to avoid the hypnotic properties of the higher 4-5 mg doses.
- For tardive dyskinesia (TD): 10 mg daily of a controlled-release formulation.
- As treatment for solid tumors in combination with conventional therapy: 10-50 mg along with radiotherapy, chemotherapy, or interleukin 2 (IL-2). Melatonin is typically started 7 days before the start of chemotherapy and continued throughout full treatment course.
- For treatment of prostate cancer that has spread to other sites (metastatic cancer) and is resistant to triptorelin used alone: 20 mg taken daily has been used in combination with 3.75 mg of triptorelin injected into the muscle every 28 days.
- For prevention and treatment of lowered clot-forming cells (thrombocytopenia) associated with cancer chemotherapy: 20 mg each evening.
- For benzodiazepine withdrawal in elderly people with insomnia: 2 mg of controlled-release melatonin taken at bedtime for 6 weeks (the benzodiazepine dosage is reduced 50% during the second week, 75% during weeks 3 and 4, and stopped during weeks 5 and 6) and continued up to 6 months.
- For prevention of cluster headache: an evening dose of 10 mg.
- For reducing anxiety before surgery in adults: 0.05 mg/kg under the tongue.
- For reducing nicotine withdrawal symptoms: 0.3 mg orally 3.5 hours after stopping smoking.