Chronic antidepressant treatment accelerates kindling epileptogenesis in rats

Abstract Objectives Due to the high comorbidity of epilepsy and depression, antidepressant treatment is commonly indicated for patients with epilepsy. Studies in humans and animal models suggest that selective serotonin reuptake inhibitors (SSRIs) may reduce seizure frequency and severity, and these drugs are generally considered safe for use in epilepsy. No studies have investigated the effects of SSRIs on epileptogenesis, the neurobiological process underlying the development of the epileptic state. Methods The effect of continuous infusion of the SSRI, fluoxetine (10 mg/kg/day sc), versus vehicle control on amygdala kindling was examined in adult male Wistar rats. Seizure threshold and kindling rates were compared between SSRI-treated rats and controls. The study was then repeated examining the effect of a different SSRI, citalopram (10 mg/kg/day sc), versus vehicle control. Hippocampal mRNA expression of the serotonin transporter (SERT) and the 5-HT1A receptor was examined in the brains of the rats post-mortem. Results Treatment with either fluoxetine or citalopram significantly accelerated kindling epileptogenesis, as evidenced by fewer stimulations to reach Class V seizures compared to their respective vehicle-treated group (p < 0.01 for both drugs). Seizure duration was also increased in fluoxetine-treated rats. No differences in seizure threshold were observed between treatments (p > 0.05). mRNA analysis did not reveal any molecular changes which were common to both treatments. Conclusions The rate of epileptogenesis in rats is enhanced by chronic treatment with SSRIs. This could potentially have implications regarding the effect of SSRIs on the development or progression of human epilepsy.