What are the treatment options for a suspected melatonin overdose?

Melatonin Overdose Management

Melatonin overdose should be managed with supportive care only, including monitoring of vital signs, airway protection if consciousness is impaired, and observation until symptoms resolve—there is no specific antidote, and gastric lavage is only indicated for massive ingestions presenting within 1-2 hours. 1

Clinical Presentation and Severity Assessment

Melatonin has remarkably low toxicity potential despite widespread availability and increasing overdose reports. 1 The clinical presentation varies by dose and co-ingestions:

Expected Symptoms

• Excessive drowsiness and lethargy are the primary manifestations, even with massive overdoses (up to 900 mg reported). 1
• Altered mental status ranging from confusion to minimally responsive states can occur with very large ingestions. 1, 2
• Disorientation has been documented even with moderate overdoses (24 mg). 2
• Fragmented sleep paradoxically can occur. 3

Serious Complications (Rare)

• Respiratory depression requiring mechanical ventilation has occurred in 5 pediatric cases during 2012-2021. 4
• Two pediatric deaths were reported during this same period, though details of co-ingestions are unclear. 4
• Seizures have been reported in 4 cases. 3

Immediate Management Algorithm

Step 1: Initial Stabilization

• Assess airway, breathing, and circulation with particular attention to level of consciousness. 1
• Obtain vital signs including heart rate, blood pressure, respiratory rate, and oxygen saturation—these typically remain stable even in significant overdoses. 1
• Calculate Glasgow Coma Scale if altered mental status is present. 1

Step 2: Decontamination Considerations

• Gastric lavage may be considered only for massive ingestions (>100 tablets or equivalent) presenting within 1-2 hours of ingestion. 1
• Activated charcoal is not routinely recommended as melatonin has low toxicity and rapid absorption.
• Do not induce emesis given risk of aspiration with altered consciousness.

Step 3: Laboratory Evaluation

• Complete blood count to assess for leukocytosis (may be elevated as stress response). 1
• Basic metabolic panel to evaluate renal function. 1
• Liver function tests to assess hepatic function. 1
• Urine drug screen to identify co-ingestions, particularly benzodiazepines which commonly accompany melatonin overdoses. 1
• Blood levels of co-ingested substances if suspected (e.g., benzodiazepines, other sedatives). 1

Note: Melatonin blood levels are not clinically useful for management decisions. 2

Step 4: Supportive Care

• Monitor vital signs continuously until patient is alert and oriented. 1
• Maintain airway protection with positioning or intubation if Glasgow Coma Scale <8. 1
• Provide IV fluids for hydration and to maintain renal perfusion.
• Observe for 24-48 hours as recovery may take up to 32 hours post-ingestion even with supportive care. 1

Special Considerations and Drug Interactions

Benzodiazepine Co-ingestion

Melatonin may interact with benzodiazepines to produce enhanced sedation beyond what would be expected from either agent alone. 2 This is the most common clinically significant co-ingestion pattern. 1

Potential Antagonists

• Naloxone and flumazenil have been reported to antagonize melatonin effects, though this is not standard practice and evidence is limited. 2
• These agents should only be used if opioid or benzodiazepine co-ingestion is confirmed and clinically indicated for those substances specifically.

Patients on Chronic Medications

• Warfarin users may have enhanced anticoagulant effects. 5
• Patients with epilepsy may be at increased seizure risk. 5, 3
• Diabetic patients should have glucose monitoring as melatonin can impair glucose tolerance. 5

Pediatric-Specific Considerations

Pediatric melatonin ingestions increased 530% from 2012-2021, with unintentional ingestions in children ≤5 years accounting for the majority of serious outcomes. 4

Age-Specific Risk Factors

• Children ≤5 years are at highest risk for unintentional ingestion and serious outcomes due to exploratory behavior and inability to communicate symptoms. 4
• Adolescents more commonly have intentional overdoses, often with co-ingestions. 1

Pediatric Management Differences

• Lower threshold for hospital admission given the two reported pediatric deaths. 4
• Extended observation period (minimum 24 hours) for children with altered mental status. 4
• Consider child protective services consultation for unintentional ingestions to assess home safety. 4

Disposition and Follow-up

Admission Criteria

• Any patient with Glasgow Coma Scale <12 should be admitted for observation. 1
• Pediatric patients with any altered mental status should be admitted. 4
• Co-ingestion with other sedatives warrants admission. 1
• Intentional overdoses require psychiatric evaluation before discharge. 1

Discharge Criteria

• Patient is alert and oriented to person, place, and time.
• Vital signs are stable for at least 6 hours.
• No co-ingestions identified or co-ingested substances have been adequately treated.
• Safe discharge plan is in place, including psychiatric follow-up for intentional ingestions. 1

Prevention Counseling

Melatonin is regulated as a dietary supplement, not a drug, leading to easy availability and lack of child-resistant packaging in many products. 4

Key Prevention Messages

• Store melatonin in locked cabinets out of reach of children. 4
• Choose products with child-resistant packaging when available.
• Educate families that "natural" does not mean "harmless"—melatonin is pharmacologically active. 2
• Report adverse events to FDA MedWatch to improve safety surveillance. 4

Important Caveats

Melatonin should not be considered a benign agent in overdose despite its generally favorable safety profile at therapeutic doses. 2 The increasing number of pediatric ingestions and rare but serious outcomes (mechanical ventilation, death) underscore the need for appropriate caution and monitoring. 4 The lack of FDA regulation as a drug means product purity and actual melatonin content may vary significantly from labeled amounts, potentially affecting overdose severity. 6