Melatonin and Seizure Threshold
Melatonin does not appear to decrease seizure threshold; in fact, recent evidence suggests it may have anticonvulsant properties and could potentially reduce seizure frequency in certain patients.
Effects of Melatonin on Seizure Activity
The most recent and highest quality evidence from a 2023 randomized, double-blind, placebo-controlled trial found that melatonin as add-on therapy reduced seizure severity in patients with idiopathic generalized tonic-clonic seizures, suggesting potential anticonvulsant rather than proconvulsant properties 1
A systematic review found no evidence of melatonin worsening seizures, with most studies showing either no effect or potential improvement in seizure control 2
A pilot study demonstrated that melatonin (10 mg daily) significantly decreased diurnal seizures compared to placebo in patients with intractable epilepsy, with no seizure aggravation or major side effects documented 3
Mechanism and Physiological Considerations
Melatonin is the major sleep-promoting hormone under circadian control, with levels peaking just before sleep initiation 4
The physiological significance of melatonin in non-photoperiodic species (like humans) is not fully understood, but it appears to have stable intraindividual profiles despite large interindividual differences in production 4
Melatonin has been proposed to have neuroprotective and antiexcitotoxic effects through inhibition of brain glutamate receptors and nitric oxide production, which may explain its potential anticonvulsant properties 5
Clinical Applications and Safety
A double-blind, cross-over, placebo-controlled trial in patients with mental retardation and epilepsy found melatonin improved sleep latency without overall worsening of seizure frequency, though occasional individual variations were noted 6
Melatonin has been investigated as an intervention for preventing delirium and improving cognitive outcomes in perioperative settings, with mixed results but generally good safety profiles 4
The American Academy of Sleep Medicine found weak evidence against clinically significant efficacy of melatonin for sleep onset insomnia, but importantly, no significant adverse events were reported compared to placebo across multiple studies 4
Important Caveats and Considerations
Results from melatonin studies should be interpreted cautiously in patients with disease states or medication use that affects the liver or kidney, as these can influence melatonin metabolism and excretion 4
Individual responses to melatonin may vary, and while overall evidence suggests no general worsening of seizures, monitoring is still recommended when initiating therapy in epileptic patients 2, 6
The timing of melatonin administration may be important, as it affects circadian rhythms, and improper timing could potentially disrupt sleep-wake cycles 4
Light exposure significantly suppresses melatonin synthesis, which should be considered when evaluating melatonin's effects or administering supplemental melatonin 4