Melatonin as a Proconvulsive Hormone in Humans

Abstract

The pineal gland and melatonin exert a major influence in the control of brain electrical activity and have been shown to be involved in seizure and sleep mechanisms. Since pinealectomy has been reported to result in seizures in experimental animals, it is assumed that melatonin has anticonvulsant properties. Indeed, limited studies in humans with temporal lobe epilepsy indicate that melatonin attenuates seizure activity. In the present communication we present evidence, based on magnetoencephalographic (MEG) brain measurements, that melatonin may exert proconvulsive activity in humans as well. The proconvulsive properties of melatonin may explain several phenomena associated with epilepsy such as the increased occurrence of seizures at night when melatonin plasma levels are 5 to 8-fold higher than during the day and the observed exacerbation of seizures premenstrually and during pregnancy as well as the attenuation of seizures in the menopause. Furthermore, our findings suggest that anticonvulsants which decrease melatonin secretion, such as the benzodiazepines, may exert their antiepileptic activity by attenuating nocturnal melatonin secretion. Finally, we propose that patients with nocturnal epilepsy or those experiencing exacerbation of seizures premenstrually may benefit from the administration of agents which block the secretion or action of melatonin.

Sleep in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder

“…79 A few studies have reported a possible increase in seizure activity by melatonin. 80,81 However, in another review, Jain and Besag 82 analyzed 27 studies on the use of melatonin and found no significant overall increase in seizure activity in most studies, and those that did report an increase in seizure activity had patients with preexisting uncontrolled seizures.…”

Melatonin utility in neonates and children

“…Experimentally, melatonin enhanced low Mg 2þ -induced epileptiform activity in the hippocampus, 85 whereas melatonin antagonists delayed the onset of pilocarpine-induced seizures. 86 Clinically, melatonin has been shown to induce electroencephalographic abnormalities in patients with temporal lobe epilepsy 87 and increase seizure activity in neurologically disabled children. 27…”

Melatonin secretion in children with epilepsy

“…The results of the evaluation of MLT therapy in epilepsy have also been inconsistent. Initial case descriptions have suggested that melatonin may either reduce seizures [22] or exacerbate the course of epilepsy [23,24]. Recent larger studies of children with epilepsy have shown that exogenous melatonin decreased frequency and duration of seizures and improved quality of sleep in children and adults with intractable epilepsy [22,[25][26][27].…”