Authors :
Presenting Author: Stephanie Simon-Medrano, Bio. – Instituto Nacional de Psiquiatría, "Ramón de la Fuente Muñiz"
Alejandro Váldes-Cruz, PhD – Instituto Nacional de Psiquiatría, "Ramón de la Fuente Muñiz"
Diana Larissa Castillo-Villegas, Bio. – Instituto Nacional de Psiquiatría, "Ramón de la Fuente Muñiz"
Ilse Julia Romero-Elizalde, BS – Instituto Nacional de Psiquiatría, "Ramón de la Fuente Muñiz"
Rationale:
Between 20-55% of patients with epilepsy also suffer from depression1. Shared physiological mechanisms have been identified, such as loss of volume in the hippocampus, amygdala, and orbitofrontal cortex, as well as dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and neurotransmitter systems like serotonin2,3. The interaction of these two conditions complicates patient management, where inappropriate medication can lead to negative effects. For depression, Selective Serotonin Reuptake Inhibitors (SSRIs) like Fluoxetine (FLX) and Citalopram (CIT) are the primary treatment options4. However, there are concerns that SSRIs might have a pro-epileptic effect5. This study contrasts the effects of depression models and SSRI treatment on epileptogenesis. Methods:
Depressive-like behavior was induced using the Chronic Unpredictable Stress (CUS) and Social Isolation (SI) models, alongside administration of FLX or CIT (10 mg/kg SC) for 21 days. Electrodes were then implanted in the hippocampus (HipD), prefrontal cortex, and occipital cortex bilaterally. Pentylentetrazol (PTZ) was used as a model of ictogenesis, administered in cumulative doses (20 or 10 mg/kg i.p. every 10 minutes) until status epilepticus (SE) was achieved.Results:
FLX treatment reduced the severity and duration of generalized clonic convulsions (GCC), while CIT shortened the latency and increased the number of paroxysms and GCCs. In non-depressed rats, administration of both SSRIs resulted in longer GCC duration and reduced the latency to SE.
Conclusions: In conclusion, the differential effects of these two drugs in non-depressed subjects exacerbate seizures, underscoring the need for accurate diagnosis when prescribing SSRIs in patients with this comorbidity.
Funding: Proyecto Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz NC123240.1