Antidepressants and

seizure risk
Chidiebere Eze
PGY-1 Pharmacy Resident
Ball memorial hospital
Sept 27, 2017
Objectives
Case
• WF is a 53 yom MMA fighter with post traumatic epilepsy who
presents with a BP of 201/124, HR 119 and recurrent seizure
• Allergies:
• NKA
• Neurologic review of systems:
• Seizure, confusion (postictal), no headache, numbness, tingling,
weakness or dizziness
• EKG was done with diagnosis of recurrent seizure
• Supposed to be on Keppra or phenytoin
• None listed on home medication list
• Plan to empirically treat with keppra
Case
• PMH:
• Afib, DVT with hx of PE, HTN, TIA, Anemia, Mycotic aneurysm,
Hep C, MVA with C-spine injury, TBI with resultant seizures
• SH:
• Alcohol abuse, former tobacco user
• ROS:
• Cardiovascular: DVT, Afib
• GI: Hepatitis
• Neurological: Seizure grand mal, confusion
• Psychiatric: Substance abuse
HPI
• Off opiate therapy for ~9 days
• Progressively worsening back pain
• Denies fever/chills
Pertinent home medications
• Acetazolamide 250 mg daily
• Aspirin 81 mg daily
• Diltiazem 60 mg TID
• Metoprolol tartrate 25 mg, 75mg BID
• Pregabalin 150 mg TID
• Paroxetine 30 mg daily
Labs
• Na: 144 • BP: 201/124
• K: 3.3 • HR: 119
• Cl: 127 • RR: 18
• CO2: 15 • Temp: Afebrile
• BUN: 13 • A1C: 4.8%
• Cr: 0.46 • QTc: 486
• Glu: 164 • LVEF: 50%, DDI
• Ca: 5 • CHADS2-Vasc: 4
• A1C: 4.8% • INR: 1.15
In-patient pertinent meds
• Acetazolamide 250 mg daily
• Aspirin 81 mg daily
• Diltiazem 60 mg TID
• Metoprolol tartrate 25 mg, 75mg BID
• Pregabalin 150 mg TID
Day 2
• Refused all medications except IV meds and zolpidem
• Levetiracetam – makes him “feel funny”

• Seizures
• Planned to check phenytoin and levetiracetam levels
• hx. of TBI. Medication non-compliance? or Opiate withdrawal?
Day 3
• BP: 96/79, HR 49, RR12

• MD discussed the importance of compliance as pregabalin may also

provide an anticonvulsant effect if taken consistently
• Pt was receptive, resumed taking medications

• Plan for seizure at home

• Continue pregabalin, restart levetircetam
• Counsel on adherence with regimen

• Patient left hospital against medical advice

Pharmacology
• Excitation: (too much)
• Currents:
• Inward Na+, Ca++
• NT: Glutamate, NMDA receptor
• Duty: Boosts AP

• Inhibition: (too little)

• Currents:
• Inward CL-
• Outward K+
• NT: GABA, GABA receptor
• Duty: Stops AP
• f
Anti-epilepsy
• NICE guidelines
• National Institute for Health and Care Excellence

• Generalized tonic-clonic seizures

• First line:
• Sodium valproate, lamotrigine
• Alternative first line treatment
• Carbamazapine, oxcarbazepine
• Adjunctive treatment
• Clobazam, lamotrigine, levetiracetam, sodium valproate,
topiramate
• f
Antidepressants
• Decrease seizure threshold:
• Bupropion (Wellbutrin, Zyban)
• Dose-related, titrate dose slowly, not to exceed 450 mg/day
• TCA
• Avoid supratherapeutic doses
• Block GABAA receptors
• Caution in high risk patients or with known diagnosis of epilepsy.
• Titrate slowly
• Monitor for adverse events.
• SSRI/SNRI (rare)
• Risk of serotonin syndrome
• Can cause seizures in 1–2 % of affected patients
• Do not withhold in patients with epilepsy
Antipsychotics
• Most antipsychotics can lower the seizure threshold
• Clozapine
• dose-dependent fashion; 300–600 mg/day resulted in a seizure
incidence of 1.8% and >600 mg/day showed a seizure incidence
of 4.4%.5
• Titrate slowly
• Obtain serum level before exceeding 600 mg/day dose.6
• Consider other therapies:
• risperidone, molindone, thioridazine, haloperidol, pimozide,
trifluoperazine, or fluphenazine.6
• Retrospective study
• Doxepin improved depression, decreased seizure frequency
• Double-blind trial
• Improvements in depression with amitryptyline, nomifesene and
placebo
• No increase in seizure frequency
• “All non-monoaminase oxidase inhibitors decrease seizure
threshold”
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605864/
Conclusion
• Few studies investigate antidepressants in patients with
epilepsy
• Treatment guide:
• Monitor anticonvulsant medication levels
• SSRI
• Some may still be the most acceptable antidepressants
• Monitor carefully
• Resistant illnesses:
• Electroconvulsive therapy
• Psychosurgery
• Deep brain stimulation
• Transcranial magnetic stimulation
Goal
• Recognize patients who are at increased risk of seizures
• Recognize drugs that lower the seizure threshold.
• Recognize conditions that increase the risk of seizures include
head trauma, brain tumor, stroke, intracranial infection,
anorexia nervosa, and other congenital abnormalities.
Antidepressants and
seizure risk
Chidiebere Eze
PGY-1 Pharmacy Resident
Ball memorial hospital
Sept 27, 2017