Sudden unexpected death in epilepsy (SUDEP) is a tragic outcome of seizure disorders that primarily affect young adults suffering from refractory epilepsy. In this population, SUDEP incidence is estimated at 0.5%. While the mechanisms of SUDEP are not completely understood, it appears that the majority of such death occurs in the immediate aftermath of a general tonic-clonic seizure.

There is currently no validated preventive treatment for SUDEP. Some evidence suggest that modulation of the serotoninergic tone, and more specifically selective serotonin recapture inhibitor (SSRI) such as fluoxetine, might prevent SUDEP. Indeed, fluoxetine prevents seizure-induced lethal central apneas in DBA/2 and DBA/1 mice, one of the few animal models of SUDEP. Furthermore, serotoninergic bulbar nuclei are known to play a major role in the control of breathing, especially during sleep and in response to repeated hypoxia.

In patients with epilepsy undergoing in-hospital video-EEG monitoring, about one third of seizures are associated with decrease in SpO2 <90%, an abnormality suspected to represent a risk factor of SUDEP. In a retrospective uncontrolled study, patients treated with SSRIs displayed less frequent ictal/post-ictal hypoxemia than patients not taking SSRIs.

The investigators project aimed at testing whether fluoxetine can reduce the risk of ictal/post-ictal hypoxemia by performing a double-blind, randomized, placebo-controlled trial in patients undergoing video-EEG monitoring as part of the pre-surgical evaluation of their focal drug-resistant epilepsy.

Inclusion Criteria:

Patient suffering from drug-resistant focal epilepsy

• Age ≥ 18 years
• Patient for whom a video-EEG monitoring of their seizures was scheduled as part of a pre-surgical assessment
• For women of childbearing age, a method of contraception considered effective by the investigator
• Patient who have given their written informed consent
• Patient accepting an interview with a psychologist and to be refered to a psychiatrist in the event that mood disorders were detected on mood scores and considered severe by the investigator and / or psychologist, leading to require psychiatric care or immediate antidepressant treatment
• Patient with a social security number

Exclusion Criteria:

• Age < 18 years

  • Patient under legal protection
  • Pregnant or breastfeeding women
  • Hypersensitivity to fluoxetine or its excipients
  • History of other serious side effects related to an earlier prescription of fluoxetine;
  • Current suicidal ideation or history of suicide attempt
  • Manic episode
  • Disruption of liver enzymes considered material by the investigator using the following criteria:

transaminases (ALT and AST)> 2N alkaline phosphatase (ALP)> 2N gamma glutamyl transpeptidase (GGT)> 5N (performed as part of routine monitoring of epileptic patients on antiepileptic treatment. Patients often exhibit changed deemed clinically insignificant due to the enzyme-inducing effect of these drugs)

• Renal failure with creatinine clearance <30 ml / min
• Acute heart disease
• Antidepressant treatment
• Other prohibited treatment (see detailed list in protocol).