What are the contraindications for melatonin use, especially in patients with bleeding disorders, epilepsy, autoimmune disorders, kidney or liver disease, pregnant or breastfeeding women, and geriatric individuals?

Contraindications of Melatonin

Melatonin has no absolute contraindications established in major clinical guidelines, but should be used with extreme caution or avoided in patients with bleeding disorders (especially those on anticoagulation), active epilepsy, pregnancy/breastfeeding, and severe hepatic or renal impairment. 1, 2

Bleeding Disorders and Anticoagulation

Melatonin demonstrates antiplatelet effects and should be avoided in patients with bleeding disorders or those taking warfarin. 2, 3

• The American Academy of Sleep Medicine specifically recommends caution in patients taking warfarin due to potential interactions reported to the World Health Organization 1, 2
• A pediatric case report documented clinically significant antiplatelet effects from melatonin transmitted through breast milk, resulting in bleeding episodes that resolved only after maternal melatonin discontinuation 3
• For patients requiring anticoagulation therapy (including those with cancer-associated thrombosis), melatonin should be avoided given the absolute contraindication of anticoagulants in patients with underlying bleeding disorders 4
• If melatonin must be used in anticoagulated patients, monitor INR more frequently when initiating or discontinuing therapy 5

Epilepsy and Seizure Disorders

Exercise extreme caution when prescribing melatonin to patients with epilepsy, as conflicting evidence exists regarding seizure risk. 1, 2

• The American Academy of Sleep Medicine recommends caution based on case reports of adverse effects in epileptic patients 1, 2
• Clinical data shows melatonin induced electroencephalographic abnormalities in patients with temporal lobe epilepsy and increased seizure activity in neurologically disabled children 6
• Paradoxically, some studies show anticonvulsant properties, particularly in juvenile intractable epilepsy, but the high doses required (which may cause seizure inhibition) can induce cognitive and motor impairment 6
• The risk-benefit ratio favors avoidance in active epilepsy unless under close neurological supervision 6

Autoimmune Disorders

Melatonin has immunosuppressive and immunomodulatory properties that theoretically could affect autoimmune disease activity. 7

• While melatonin possesses anti-inflammatory and immunosuppressive actions, no specific contraindications for autoimmune disorders are established in major guidelines 7
• The lack of guideline-level contraindications suggests cautious use is acceptable, but patients should be monitored for disease flare 7

Kidney and Liver Disease

Avoid melatonin in severe hepatic or renal impairment due to altered metabolism and clearance. 1, 2

• The American Academy of Sleep Medicine notes that patients with liver disease may experience enhanced sensitivity to melatonin, making lower doses more appropriate 1
• Melatonin is primarily metabolized hepatically, and severe liver dysfunction could lead to accumulation and increased adverse effects 8
• For patients with creatinine clearance <30 mL/min/1.73 m², exercise caution as melatonin clearance may be impaired (though this specific threshold is established for DOACs, not melatonin) 4

Pregnancy and Breastfeeding

Melatonin should be avoided during pregnancy and breastfeeding due to insufficient safety data and documented transmission through breast milk with pharmacological effects. 4, 3

• All medications used for weight management (which includes sleep aids in obesity guidelines) are contraindicated in women who are or may become pregnant 4
• A case report demonstrated that melatonin passes into breast milk in sufficient quantities to cause antiplatelet effects and bleeding in a breastfed infant 3
• Women of reproductive potential should be counseled regarding reliable contraception if melatonin is prescribed chronically 4

Geriatric Patients with Dementia

The American Academy of Sleep Medicine explicitly recommends avoiding melatonin for irregular sleep-wake rhythm disorder in older adults with dementia due to lack of benefit and potential harm. 1

• Detrimental effects on mood and daytime functioning have been observed in dementia patients receiving melatonin 1
• This represents one of the few population-specific recommendations against melatonin use in major guidelines 1

Additional Precautions and Relative Contraindications

Several other clinical scenarios warrant extreme caution or avoidance:

• Photosensitizing medications: Patients require periodic ophthalmological and/or dermatological monitoring due to potential interactions 2
• Impaired glucose tolerance/diabetes: Melatonin has been associated with impaired glucose tolerance in healthy individuals after acute administration; monitor fasting glucose periodically in at-risk patients 1, 2
• Depression: Melatonin has been associated with increased depressive symptoms in some individuals 2, 8
• Cardiovascular disease on warfarin: While melatonin appears safe in cardiac patients generally (including perioperatively in cardiac surgery), the combination with warfarin requires heightened vigilance 5, 2

Critical Dosing Considerations to Minimize Risk

When melatonin is deemed appropriate despite precautions, start with the lowest effective dose:

• Begin with 3 mg of immediate-release melatonin, as higher doses (10 mg) cause receptor desensitization and more frequent adverse effects including morning headache, sleepiness, and gastrointestinal upset 1
• Administer 1.5-2 hours before desired bedtime 1, 2
• Choose United States Pharmacopeial Convention Verified formulations to ensure reliable dosing and purity, as melatonin is regulated as a dietary supplement with variable quality 1, 2
• Limit duration to 3-4 months maximum for chronic insomnia due to insufficient long-term safety data 1

Common Pitfalls to Avoid

• Do not assume melatonin is universally safe because it is available over-the-counter; it has significant pharmacological effects including antiplatelet activity, receptor-mediated actions, and drug interactions 3, 8
• Do not prescribe melatonin in the morning or afternoon, as this worsens circadian misalignment 2
• Do not ignore concurrent medications: Document all medications before recommending melatonin to review for potential interactions, particularly warfarin, photosensitizing agents, and medications affecting glucose metabolism 2
• Do not use in dementia patients for irregular sleep-wake rhythm disorder, as guidelines explicitly recommend against this 1