The Efficacy of a Subanesthetic Doses of IV Ketamine in the Treatment Drug Resistant Epilepsy

This is an open label pilot study that will evaluate the effectiveness of a sub-anaesthetic dose (0.5mg/kg) of IV Ketamine in Drug Resistant Epilepsy Patients. Mood assessments will also be administered. The study consists of 3 phases:

Screening : Seizure diary will be prospectively filled for 4 weeks and subjects must have at least 4 seizures in 28 days to proceed to the treatment phase. Baseline mood assessment will be performed (NDDI-E, QOLIE-10, GAD 7 )

Treatment Phase: This phase will consist of 6 study visits (3 visits/ week for 2 weeks). Patients will receive 0.5mg/kg Racemic ketamine IV over 40 min three times a week (M, W, F) for 2 consecutive weeks.

Treatment Visit 1: Monday Week 5(baseline seizures diary collected) Treatment Visit 2: Wednesday Week 5 Treatment Visit 3: Friday Week 5 Treatment Visit 4: Monday Week 6 Treatment Visit 5: Wednesday Week 6 Treatment Visit 6: Friday Week 6 (Mood assessments performed prior to infusion)

Post- Treatment Phase : This phase will consist of 5 post infusion safety assessments and 3 post-treatment assessments.

Post-Infusion Safety Assessment 1: Saturday Week 6 (Adverse Event Assessment) Post-Infusion Safety Assessment 2: Sunday Week 7 (Adverse Event Assessment) Post-Infusion Safety Assessment 3: Monday Week 7 (Adverse Event Assessment) Post-Infusion Safety Assessment 4: Monday Week 8 (Adverse Event Assessment) Post-Infusion Safety Assessment 5: Monday Week 9 (Adverse Event Assessment)

Post-Treatment Assessment 1: phone call week 10 (Seizure diary collection, mood assessments performed) Post-Treatment Assessment 2: phone call week 14 (Seizure diary) Post-Treatment Assessment 3: phone call week 18 (Seizure diary collection, mood assessments performed)

Inclusion criteria

• Provision of signed and dated informed consent form
• Adults (18 years or older)
• Cognitively impaired adults are not excluded (i.e. will be included in the study)
• Established diagnosis of Drug Resistant Epilepsy (DRE) i.e. failed two or more appropriately chosen anti-seizure medications (ASMs)
• EEG consistent with focal or generalized epilepsy
• Patients must have >4 focal aware, focal impaired aware, focal to bilateral tonic clonic or generalized tonic clonic seizures per month.
• Patients can be on >/= 1 anti-seizure medication (ASM) at the time of enrollment on stable doses 12 weeks prior to initiation
• Patients on Epilepsy devices: Vagal nerve stimulator (VNS), Deep brain stimulator (DBS) or Responsive Nerve Stimulator (RNS) must have remained stable for at least 4 weeks before the screening visit. Adjustment of devices is not allowed during the study.

Exclusion criteria

• Patients <18 years of age
• Pregnant women
• Women that are breast feeding
• Patients who had >21 days of seizure freedom in the last year.
• Patients with a history of status epilepticus within 3 months of screening
• Patients with a history of alcoholism of drug misuse within the last 2 years
• Unstable medical illness
• Serious or imminent suicidal or homicidal risk
• Patients with cardiovascular disease
• Patients with schizophrenia
• Patients with history of aneurysm or aortic dissection, arteriovenous malformation and intracerebral hemorrhage
• Patients that are immobile i.e. wheel chair bound, bed ridden individuals
• Patients on psychostimulants (amphetamines, methylphenidate etc.) and Monoamine oxidase inhibitors (selegiline, isocarboxazid, phenelzine etc.)