Significant Changes in Serotonin Levels Observed Following Epileptic Seizures

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Investigators sought to examine whether seizures are capable of causing changes in serotonin levels in the peripheral circulation.

Significant changes occur in peripheral serum serotonin levels following generalized (nonfocal) epileptic seizures, with inverse associations identified between serotonin levels and seizure duration. These findings possibly suggest a role of serotonin in postseizure recovery, according to a prospective, multicenter study published in Epilepsia.

Patients diagnosed with intractable epilepsy were enrolled in the study and were subsequently categorized as having either focal to bilateral tonic-clonic seizures (FBTCS) and generalized tonic-clonic seizures (GTCS) of genetic generalized epilepsy (n=19) or focal seizures alone (n=26). Peripheral capillary oxygen saturation was assessed using pulse occimetry, and serotonin levels were obtained by measuring postictal and interictal venous blood samples. Deviations from the normal laboratory reference serotonin values of 21 to 321 ng/mL represented the primary measurement/outcome.

Following GTCS and FBTCS, postictal serotonin levels were found to be higher compared with interictal levels (P =.002). There was no significant difference between GTCS/FBTCS and focal seizures in terms of postseizure serotonin levels (P =.941). Investigators found a significant difference between patients with generalized and focal seizures regarding postictal and interictal changes in serum serotonin levels (P =.027). Specifically, there was an inverse association between change in serotonin level and reduced duration of generalized seizures in the tonic phase (P =.03). Additionally, there was a significant association between increased interictal serotonin level and reduced duration of postictal generalized electroencephalogram suppression in this cohort (P =.04).

Limitations of the study include the relatively small number of patients and the lack of a nonseizure comparator group.

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Although it is unclear as to how higher serum serotonin levels were associated with shorter duration of PGES in this study, the investigators theorize that it is “possible that serotonin plays a role in early recovery by reducing seizure severity.” The investigators also suggest that “the exertion associated with generalized seizures may lead to alterations similar to other forms of exercise” in postseizure serotonin levels.


Murugesan A, Rani MRS, Hampson J, et al. Serum serotonin levels in patients with epileptic seizures. Epilepsia. 2018;59(6):e91-e97.