title: The antidepressants citalopram and reboxetine reduce seizure frequency in rats with chronic epilepsy.
abstract: OBJECTIVE
  For a long time, antidepressants have been thought to possess proconvulsant properties. This assumption, however, remains controversial, since anticonvulsant effects have been attributed to certain antidepressants. To date, it remains unclear which antidepressants can be used for the treatment of depression in patients with epilepsy. In this respect, studies investigating the convulsant liability of antidepressants in a chronic epilepsy model can give valuable information. The present study was designed to determine the seizure liability of citalopram and reboxetine in the kainic acid-induced post-status epilepticus model for temporal lobe epilepsy.
  
  
  METHODS
  Two months after the induction of status epilepticus, chronic epileptic rats (n = 16) were video-electroencephalography (EEG) monitored during seven consecutive weeks. Weeks 1, 3, 5, and 7 served as sham weeks during which the rats received intraperitoneal saline injections for four consecutive days, followed by a 3-day sham washout period during which no injections were given. During weeks 2, 4, and 6, rats received intraperitoneal injections with either citalopram (5, 10, and 15 mg/kg, once daily, n = 8) or reboxetine (10, 20, and 30 mg/kg, twice daily, n = 8) for 4 days, again followed by a washout period of 3 days. Drugs were administered in a randomly assigned fixed-dose regimen per week. Each rat served as its own control. The drug doses were selected based on the doses reported to have antidepressant effects in rats.
  
  
  RESULTS
  Citalopram significantly decreased the spontaneous seizure frequency at the highest dose tested, that is, the mean number of seizures decreased from 12.8 seizures to 8.8 seizures per week (31%) after treatment with 15 mg/kg citalopram. This dose also significantly decreased the cumulative seizure duration. Administration of 5 and 10 mg/kg citalopram did not alter the seizure frequency. The two highest doses of reboxetine significantly decreased the spontaneous seizure frequency, that is, 20 mg/kg reboxetine decreased the seizure frequency from 14.1 to 7.9 (44%) and 30 mg/kg reboxetine decreased the seizure frequency from 11.8 to 7.2 (39%). In addition, both doses significantly decreased the cumulative seizure duration. Administration of 10 mg/kg reboxetine did not alter seizure frequency. Citalopram and reboxetine had no effect on seizure severity and seizure duration in any of the doses tested.
  
  
  CONCLUSIONS
  In general we can conclude that antidepressant doses of citalopram and reboxetine have, depending on the dose, an anticonvulsant effect or no effect on spontaneous seizures in the kainic acid-induced post-status epilepticus rat model.
authors.affiliation: Center for Neurosciences, Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium.
authors.forename: Katia
authors.initials: K
authors.lastname: Vermoesen
authors.forename: Ann
authors.initials: A
authors.lastname: Massie
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.forename: Ralph
authors.initials: R
authors.lastname: Clinckers
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D009025:Morpholines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome; D014741:Video Recording
chemical_list: D000928:Antidepressive Agents; D009025:Morpholines; D015283:Citalopram; D000077593:Reboxetine; D007608:Kainic Acid