Melatonin is a hormone that is produced naturally by the body to regulate sleep cycles. As a supplement, it is commonly used to treat insomnia and jet lag. While generally considered safe for short-term use, less is known about the long-term effects of melatonin supplementation.
Some key questions around the long-term use of melatonin include:
- Does melatonin maintain effectiveness long-term for sleep disorders like insomnia?
- Are there any side effects associated with long-term melatonin use?
- Can long-term use lead to dependence or withdrawal symptoms?
- How does long-term use impact natural melatonin production and circadian rhythms?
- Are there any interactions with other medications or health conditions?
- Is melatonin safe for long-term use in children and adolescents?
This article reviews the current research around long-term melatonin supplementation to provide answers to these key questions.
Effectiveness for Sleep Disorders
Several studies have looked at the long-term effectiveness of melatonin for insomnia and other sleep disorders with mixed results.
Some findings suggest melatonin can maintain efficacy over time. A 2011 meta-analysis of 19 studies concluded that melatonin remained effective for primary insomnia after three months of use.1 However, a panel review conducted by the Agency for Healthcare Research and Quality found less consistent results, noting that evidence on long-term melatonin use for primary insomnia was limited and unclear.2
For delayed sleep phase disorder, a condition where sleep times are shifted later, one study found that the benefits of melatonin were still present after two years of treatment.3 However, another long-term study found that the effects diminished after six months.4
Overall, it appears that melatonin may remain effective for some people with sleep disorders like insomnia and delayed sleep phase disorder, but more research is still needed on its long-term efficacy. The benefits may decrease over time for some individuals.
Side Effects
Several studies have looked at the safety profile of long-term melatonin use and have generally found minimal side effects. However, some side effects have been reported with prolonged use.
In a large meta-analysis of 19 randomized controlled trials, prolonged-release melatonin was found to be safe when used for up to 12 months. Adverse effects were infrequent and minor.5 Another systematic review found that studies on melatonin use for up to 4 years reported no serious adverse effects.6
The most commonly reported side effect from long-term melatonin use is drowsiness or fatigue, especially the morning after use. Headaches, dizziness, nausea, and irritability have also been reported.7
There is also some evidence that high doses of melatonin over the long-term may impact reproductive hormones like estrogen. One study on perimenopausal women found decreased estradiol levels after taking 6-12 mg melatonin nightly for 6 months.8
Overall, the current research suggests melatonin has a favorable safety profile with low risk of serious adverse effects. However, more research is still needed, especially on very long-term use over many years.
Dependence and Withdrawal
There is no clear evidence at this time that melatonin causes dependence or withdrawal symptoms, even with prolonged use.
Melatonin does not appear to act on pathways in the brain that are impacted by addictive substances. Studies to date have not shown withdrawal effects from melatonin related to rebound insomnia or hormone changes after stopping use, even after taking it for up to 2 years.9,10
However, very little research exists on dependence and withdrawal from melatonin, especially with very long-term use over many years. This is an area requiring further study.
Impact on Natural Melatonin Production
Some concern exists that long-term melatonin supplementation could potentially disrupt the body’s natural melatonin production. But current research on this question is limited.
One study on the long-term use of melatonin in children with neurological disorders found no effects on endogenous melatonin levels compared to controls after 2 years of treatment.11
However, other studies have shown that melatonin can downregulate its own receptors after prolonged use, which could theoretically impact natural melatonin signaling over time.12 More longitudinal research is needed to conclusively determine the effects of long-term supplementation on endogenous melatonin production.
Circadian Rhythm Effects
Related to natural melatonin production, some research indicates that long-term melatonin use may impact circadian rhythms, the body’s internal clock. However, results are mixed.
A 12-month study in primary insomnia patients found no significant disruptions to circadian rhythms as assessed by circadian phase markers.13 But other studies have found alterations in circadian timing and decreased circadian amplitude with prolonged melatonin administration.14
These circadian changes could potentially lead to effects on sleep quality over time. Additional research is warranted, especially research replicating real-world settings and dosing regimens.
Drug and Disease Interactions
Some concerns exist around potential interactions between long-term melatonin use and other medications or health conditions. However, most evidence does not point to major issues thus far.
One area of concern is anticoagulants like warfarin, as one study found melatonin may increase anticoagulation activity after two weeks.15 However, two longer 12-week studies found no significant interactions between melatonin and anticoagulants.16,17
For interactions with other drugs like benzodiazepines, SSRIs and antihypertensives, studies to date have not demonstrated any clinically significant effects with long-term co-administration of melatonin.18
In patients with autoimmune diseases like rheumatoid arthritis, one study found melatonin could potentially exacerbate symptoms with prolonged use, but confirmation in larger studies is needed.19
Overall, clinically meaningful drug interactions do not appear common with long-term melatonin use based on current data. However, rigorous pharmacokinetic studies are still lacking for many drug combinations and patient populations.
Use in Children and Adolescents
While melatonin is often used short-term in children for sleep issues, less is known about long-term use and the potential effects on development.
Several studies have found that prolonged-release melatonin is safe for children and adolescents with insomnia or autism spectrum disorder for up to 18 months of treatment, with low rates of adverse effects.20,21
However, some experts recommend melatonin only be used long-term in pediatric cases where treatment benefits clearly outweigh potential risks, due to lack of sufficient safety data.22
Concerns have particularly been raised around the potential impact of long-term melatonin use on pubertal development, due to melatonin’s effects on reproductive hormones. More rigorous longitudinal studies are needed.
Key Takeaways
– Melatonin may remain effective for some people long-term for sleep disorders like insomnia, but benefits may decrease over time. More research on long-term efficacy is warranted.
– Thus far, studies suggest melatonin has a favorable safety profile with low risk of serious adverse effects, even with prolonged use over 1-2 years. Short-term use is generally well-tolerated.
– Evidence does not point to dependence, withdrawal, or significant drug interactions with long-term melatonin supplementation based on current data.
– Effects of long-term use on natural melatonin production and circadian rhythms require more study, with some concern for potential disruptions.
– Long-term safety in children is not fully established; extended use in pediatrics warrants caution.
– Overall, melatonin is considered safe for short-term use, but more rigorous research is still needed to conclusively determine the effects of long-term, multi-year use.
Conclusion
Melatonin is widely used as an over-the-counter sleep aid, but the effects of regular, long-term use are not fully clear. Initial research suggests melatonin is generally safe and tolerated when used for one to two years, but studies are limited and lack consistently positive results. More rigorous, longitudinal research is still needed to conclusively determine the long-term impacts of melatonin supplementation on areas like circadian rhythms, hormone levels, and development in children. Melatonin’s efficacy also appears to decrease over time for some people with sleep disorders.
While melatonin is likely safe for short-term use in most people, caution is advised around prolonged use until more robust data is available. For long-term administration, potential benefits should be weighed carefully against unknown risks. As with any supplement, it is best to consult a healthcare professional before beginning melatonin treatment, especially for extended periods. With judicious and appropriate use, melatonin may continue to be a beneficial sleep and circadian aid.