Role of SSRIs as Anticonvulsants in Intractable Epileptic Patients

Abstract

SUMMARY E pilepsy is a common group of neurological disorders defined by unprovoked seizures; Seizures can be distressing, harmful and even fatal. There is a high incidence of psychiatric comorbidity in people with epilepsy particularly depression, especially in (TLE). As temporal lobe epilepsy with Mesial temporal sclerosis is focal type of epilepsy resistant to medical treatment affected by stressors. Stressors at all developmental stages – prenatal, postnatal and in adult life which have effect in brain serotonergic function. Serotonergic receptors play a role epileptogenesis in the CNS, e.g. 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT3 and 5-HT7 receptors are present on cortical and/or hippocampal glutamatergic or GABAergic neurons or terminals. Serotonin is monoamine neurotransmitter found centrally & peripherally with several different types (5-HT) receptors 7 distinct families & more than 20 subtypes. There is decrease in 5HT1A receptors in TLE and decreased hippocampal volume that is attributed to psychiatric and cognitive impairment. Epilepsy is usually associated with depression which is suggestive of a common etiology. Disrupted production of adult-born hippocampal granule cells in both disorders may contribute to this coincidence. Chronic stress and depression are associated with decreased granule cell neurogenesis. Epilepsy is associated with increased production – but aberrant integration – of new cells early in the disease and decreased production late in the disease too. In both cases, this review suggests these changes in neurogenesis play important roles in their respective diseases. Morever, they both result from dysregulation of hypothalamo pituitary adreno cortical axis and corticosteroids. If there is shared underlying pathology that can lead to both seizures and depression, then it would be expected that treatments for one condition would improve the symptoms of the other. This appears to be the case, since some treatments for depression are effective against seizures, and some anticonvulsants are effective in management of mood/affective disorders. Exposure to older generations of antidepressants (notably tricyclic antidepressants and bupropion) can increase seizure frequency. However, growing evidence suggests that newer (‘second generation’) antidepressants, such as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, have markedly less effect on excitability and may lead to improvements in epilepsy severity. In general, an increase in extracellular 5-HT levels inhibits many types of seizures and a decrease does the opposite.Several anti-epileptic drugs including phenytoin, carbamazepine, valproic acid, lamotrigine and zonisamide all cause an increase in extracellular 5-HT, and the elevated 5-HT is thought to contribute to their mechanism of action. Sudden unexpected death in epilepsy (SUDEP) is one of epileptic comorbidities has a link to serotonergic pathway, as the frequency of respiratory arrest is markedly reduced by pretreatment with SSRIs. Finally, Selective Seretonin Reuptake inhibitors should be further studied in higher doses for management of refractory epilepsy, regarding the potential benefit, to assess its anticonvulsive effect, as epilepsy is associated with several serotonin-related comorbidities.