Several human trials suggest that melatonin taken by mouth, started on the day of travel (close to the target bedtime at the destination) and continued for several days, reduces the number of days required to establish a normal sleep pattern, diminishes the time it takes to fall asleep ("sleep latency"), improves alertness, and reduces daytime fatigue. Although these results are compelling, the majority of studies have had problems with their designs and reporting, and some trials have not found benefits. Overall, the scientific evidence does suggest benefits of melatonin in up to half of people who take it for jet-lag. More trials are needed to confirm these findings, to determine optimal dosing, and to evaluate use in combination with prescription sleep aids.

Delayed sleep phase syndrome is a condition that results in delayed sleep onset, despite normal sleep architecture and sleep duration. Although these results are promising, additional research with larger studies is needed before a stronger recommendation can be made.

Several human studies report that melatonin taken by mouth before bedtime decreases the amount of time it takes to fall asleep ("sleep latency") in elderly individuals with insomnia. However, most studies have not been high quality in their designs and some research has found limited or no benefits. The majority of trials have been brief in duration (several days long), and long-term effects are not known.

There are multiple trials investigating melatonin use in children with various neuro-psychiatric disorders, including mental retardation, autism, psychiatric disorders, visual impairment, or epilepsy. Studies have demonstrated reduced time to fall asleep (sleep latency) and increased sleep duration. Well-designed controlled trials in select patient populations are needed before a stronger or more specific recommendation can be made.

Multiple human studies have measured the effects of melatonin supplements on sleep in healthy individuals. A wide range of doses has been used often taken by mouth 30 to 60 minutes prior to sleep time. Most trials have been small, brief in duration, and have not been rigorously designed or reported. However, the weight of scientific evidence does suggest that melatonin decreases the time it takes to fall asleep ("sleep latency"), increases the feeling of "sleepiness," and may increase the duration of sleep. Better research is needed in this area.

There is limited study of melatonin for improving sleep disorders associated with Alzheimer's disease (including nighttime agitation or poor sleep quality in patients with dementia). It has been reported that natural melatonin levels are altered in people with Alzheimer's disease, although it remains unclear if supplementation with melatonin is beneficial. Further research is needed in this area before a firm conclusion can be reached.

There are well over 100 laboratory and animal studies of the antioxidant (free radical scavenging) properties of melatonin. As a result, melatonin has been proposed as a supplement to prevent or treat many conditions that are associated with oxidative damage. However, well-designed trials in humans are lacking.

There is limited research of the use of melatonin in children with ADHD both on the treatment of ADHD and insomnia in ADHD children. A clear conclusion cannot be made at this time.

A small amount of research has examined the use of melatonin to assist with tapering or cessation of benzodiazepines such as diazepam (Valium®) or lorazepam (Ativan®). Although preliminary results are promising, further study is necessary before a firm conclusion can be reached.

There is limited study of melatonin given to patients with sleep disturbances associated with bipolar disorder (such as insomnia or irregular sleep patterns). No clear benefits have been reported. Further research is needed in this area before a clear conclusion can be reached.

There are several early-phase and controlled human trials of melatonin in patients with various advanced stage malignancies, including brain, breast, colorectal, gastric, liver, lung, pancreatic, and testicular cancer, as well as lymphoma, melanoma, renal cell carcinoma, and soft-tissue sarcoma. Currently, no clear conclusion can be drawn in this area. There is not enough definitive scientific evidence to discern if melatonin is beneficial against any type of cancer, whether it increases (or decreases) the effectiveness of other cancer therapies, or if it safely reduces chemotherapy side effects.

Several human trials have examined the effects of melatonin on side effects associated with various cancer chemotherapies. Although these early reported benefits are promising, high-quality controlled trials are necessary before a clear conclusion can be reached in this area. It remains unclear if melatonin safely reduces side effects of various chemotherapies without altering effectiveness.

Limited human study is available in this area. Present studies and individual cases suggest that melatonin, administered in the evening, may correct circadian rhythm. Large, well-designed controlled trials are needed before a stronger recommendation can be made.

Depression can be associated with neuroendocrine and sleep abnormalities, such as reduced time before dream sleep (REM latency). Melatonin has been suggested for the improvement of sleep patterns in patients with depression, although research is limited in this area. Further studies are needed before a clear conclusion can be reached.

It has been theorized that high doses of melatonin may increase intraocular pressure and the risk of glaucoma, age-related maculopathy and myopia, or retinal damage. However, there is preliminary evidence that melatonin may actually decrease intraocular pressure in the eye, and it has been suggested as a possible therapy for glaucoma. Additional study is necessary in this area. Patients with glaucoma taking melatonin should be monitored by a healthcare professional.

Several small studies have examined the possible role of melatonin in preventing various forms of headache, including migraine, cluster and tension-type headache (in people who suffer from regular headaches). Limited initial research suggests possible benefits in all three types of headache, although well-designed controlled studies are needed before a firm conclusion can be drawn.

Several controlled studies in patients with high blood pressure report small reductions blood pressure when taking melatonin by mouth (orally) or inhaled through the nose (intranasally). Better-designed research is necessary before a firm conclusion can be reached.

There is a lack of well-designed scientific evidence to recommend for or against the use of melatonin as a treatment for AIDS. Melatonin should not be used in place of more proven therapies, and patients with HIV/AIDS should be treated under the supervision of a medical doctor.

Based on preliminary study, melatonin is a promising therapeutic agent for IBS. Further research is needed before a recommendation can be made.

Study results have been inconsistent, with some studies reporting benefits on sleep latency and subjective sleep quality, and other research finding no benefits. Most studies have been small and not rigorously designed or reported. Better research is needed before a firm conclusion can be drawn. Notably, several studies in elderly individuals with insomnia provide preliminary evidence of benefits on sleep latency (discussed above).

Due to very limited study to date, a recommendation cannot be made for or against the use of melatonin in Parkinsonism or Parkinson's disease. Better-designed research is needed before a firm conclusion can be reached in this area.

There is very limited study to date for the use of melatonin as a treatment in periodic limb movement disorder. Better-designed research is needed before a recommendation can be made in this area.

Results are promising, with similar results reported for melatonin as for benzodiazepines such as midazolam (Versed®), and superiority to placebo. There are also promising reports using melatonin for sedation/anxiolysis prior to magnetic resonance imaging (MRI). However, due to weaknesses in the design and reporting of the available research, better studies are needed before a clear conclusion can be drawn. Melatonin has also been suggested as a treatment for delirium following surgery, although there is little evidence in this area.

Limited case reports describe benefits in patients with REM sleep behavior disorder who receive melatonin. However, better research is needed before a clear conclusion can be drawn.

Rett syndrome is a presumed genetic disorder that affects female children, characterized by decelerated head growth and global developmental regression. There is limited study of the possible role of melatonin in improving sleep disturbance associated with Rett syndrome. Further research is needed before a recommendation can be made in this area.

There is limited study of melatonin for improving sleep latency (time to fall asleep) In patients with schizophrenia. Further research is needed in this area before a clear conclusion can be reached.

There are several small, brief studies of melatonin in patients with SAD. This research is not well designed or reported, and further study is necessary before a clear conclusion can be reached.

The role of melatonin in seizure disorder is controversial. Better evidence is needed in this area before a clear conclusion can be drawn regarding the safety or effectiveness of melatonin in seizure disorder.

Several published cases report improvements in sleep patterns in young people with damage to the pineal gland area of the brain due to tumors or surgery. Due to the rarity of such disorders, controlled trials may not be possible. Consideration of melatonin in such patients should be under the direction of a qualified healthcare provider.

Based on preliminary study, melatonin may improve sleep in patients with asthma. Further studies looking into long-term effects of melatonin on airway inflammation and bronchial hyper-responsiveness are needed before melatonin can be recommended.

Although preliminary results are promising, due to weaknesses in the design and reporting of this research, further study is necessary before a firm conclusion can be reached.

At this time, the effects of melatonin supplements immediately after stroke are not clear.

Tardive dyskinesia (TD) is a serious potential side effect of antipsychotic medications, characterized by involuntary muscle movements. Limited small studies of melatonin use in patients with TD report mixed findings. Additional research is necessary before a clear conclusion can be drawn.

Increased platelet counts after melatonin use have been observed in patients with decreased platelets due to cancer therapies (several studies reported by the same author). Stimulation of platelet production (thrombopoeisis) has been suggested but not clearly demonstrated. Additional research is necessary in this area before a clear conclusion can be drawn.

It has been proposed that antioxidant properties of melatonin may be protective. Further study is necessary before a clear conclusion can be drawn about clinical effectiveness in humans.

There are several studies of melatonin use in people who work irregular shifts, such as emergency room personnel. Results are mixed. Additional research is necessary before a clear conclusion can be drawn.