What are the long-term effects of taking melatonin (melatonin)?

Long-Term Effects of Melatonin

Long-term use of melatonin beyond 3-4 months is not recommended for chronic insomnia due to insufficient safety and efficacy data, though it may be appropriate for ongoing treatment of specific circadian rhythm disorders at doses of 3-5 mg daily. 1, 2

Safety Profile for Short-Term Use

The available evidence demonstrates that melatonin has a favorable safety profile for short-term use (up to several months):

• Most common adverse effects include somnolence (1.66%), headache (0.74%), dizziness (0.74%), and nausea, which are generally mild and self-limiting 2
• Morning grogginess and "hangover" effects occur more frequently with higher doses (10 mg) due to melatonin's half-life extending into morning hours 2
• No serious adverse reactions have been documented across all age groups when used at appropriate doses 2

Critical Gaps in Long-Term Safety Data

The fundamental limitation is that efficacy and safety data for melatonin is restricted to short-term studies, and safety/efficacy in long-term treatment remains unknown. 1, 2

• Clinical trial data primarily supports melatonin use lasting 4 weeks or less 2
• Studies extending beyond 6 months of daily use are essentially non-existent in the published literature 3
• There is widespread agreement that long-term effects of exogenous melatonin have been insufficiently studied and warrant additional investigation 4

Specific Long-Term Concerns

Reproductive and Developmental Effects

Based on melatonin's physiological role, potential long-term risks include:

• Inhibition of reproductive function in adults 3
• Delayed timing of puberty when used chronically in adolescents 3
• Effects on fetal and neonatal circadian development when taken during pregnancy and lactation 3

However, one questionnaire-based study following children/adolescents using melatonin (mean dose ~3 mg) for approximately 3 years showed no significant differences in pubertal development (Tanner stages) compared to non-users 2

Metabolic Effects

• Impaired glucose tolerance has been documented in healthy individuals after acute melatonin administration 2, 5
• Periodic monitoring of fasting glucose is recommended if metabolic concerns or diabetes risk factors exist 2

Receptor Desensitization

• Higher doses (10 mg) may cause receptor desensitization or saturation, potentially disrupting normal circadian signaling mechanisms 2
• This provides a mechanistic rationale for why lower doses (3 mg) may be more effective than higher doses for long-term use 2

Mood and Cognitive Effects

• Increased depressive symptoms have been reported in some individuals 5
• In older adults with dementia, detrimental effects on mood and daytime functioning have been observed, leading to recommendations against use in this population 2

Special Populations with Extended Use Data

Pediatric Populations

The most robust long-term data exists for children:

• Studies in children with autism spectrum disorder document safe use for up to 24 months with continued efficacy 2
• One pediatric study followed children for 9 months with good tolerability 2
• The American Academy of Pediatrics considers melatonin safe for children ages 6 and older at appropriate weight-based dosing 2

Circadian Rhythm Disorders

For specific conditions requiring chronobiotic (circadian-regulating) rather than hypnotic therapy:

• Delayed sleep-wake phase disorder and non-24-hour sleep-wake rhythm disorder may require ongoing melatonin treatment 1, 2
• These conditions represent exceptions where longer-term use may be justified, as they require continuous circadian regulation 2

Product Quality and Dosing Concerns

A critical safety issue for long-term use involves product reliability:

• Melatonin is regulated as a dietary supplement in the U.S., not as a medication, raising significant concerns about purity and reliability of stated doses 1, 2, 5
• Melatonin concentration of marketed preparations varies widely between product labels and manufacturers 4
• Choose United States Pharmacopeial Convention Verified formulations for more reliable dosing and purity 2, 5

Drug Interactions Relevant to Long-Term Use

• Use with caution in patients taking warfarin due to potential interactions reported to the World Health Organization 2, 5
• Exercise caution in patients with epilepsy based on case reports 2, 5
• Patients using photosensitizing medications require periodic ophthalmological and/or dermatological monitoring 5
• Concurrent medications may interact with melatonin metabolism, potentially amplifying effects 2

Practical Management Algorithm for Extended Use

If melatonin use extends beyond 3-4 months:

1. Start with 3 mg immediate-release melatonin taken 1.5-2 hours before desired bedtime 2
2. Reassess need for continued therapy every 3-6 months 2
3. Implement periodic dose reduction attempts to minimize side effects and determine lowest effective dose 1
4. Taper frequency (every other or every third night) rather than maintaining daily use 1, 2
5. If discontinuing after prolonged use, taper gradually over several weeks to months by lowering dose by smallest increment possible in successive steps of at least several days 1, 2
6. Concurrent cognitive-behavioral therapy increases successful discontinuation rates and duration of abstinence 1, 2

Comparison to Alternative Treatments

The guidelines explicitly note that:

• Benzodiazepines and older sedative-hypnotics have well-documented risks including dependence, tolerance, and significant adverse effects with long-term use 1
• Antihistamines have potential for serious anticholinergic side effects and lack evidence for long-term efficacy 1
• Melatonin's lack of dependence potential and minimal short-term adverse effects make it preferable to these alternatives when sleep medication is necessary 6

Common Pitfalls to Avoid

• Avoid using melatonin as a first-line hypnotic for chronic insomnia when the primary issue is sleep maintenance rather than circadian misalignment 1, 2
• Do not take melatonin in the morning or afternoon, as this worsens circadian misalignment 2
• Avoid alcohol consumption, which interacts with melatonin 2
• Do not assume all melatonin products contain the labeled dose due to lack of FDA oversight 1, 2
• Higher doses are not necessarily more effective and may cause receptor desensitization 2