Efficacy of Fluoxetine Against Seizure-induced Central Apneas
Efficacy of Fluoxetine Against Seizure-induced Central Apneas
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).