What are the medications used to treat seizures?

Comprehensive Guide to Antiseizure Medications for Step 1 Preparation

Benzodiazepines are the first-line treatment for active seizures, followed by phenytoin/fosphenytoin, valproate, or levetiracetam as second-line agents based on the most recent guidelines. 1, 2

Classification of Antiseizure Medications by Mechanism of Action

Sodium Channel Blockers

• Phenytoin/Fosphenytoin: First-generation sodium channel blocker used for focal seizures and generalized tonic-clonic seizures; requires monitoring for hypotension and cardiac arrhythmias during IV administration 1
• Carbamazepine: First-generation agent effective for focal seizures; induces hepatic enzymes and has multiple drug interactions 3
• Oxcarbazepine: Second-generation carbamazepine analog with fewer drug interactions; first-line for focal epilepsy 4, 5
• Lamotrigine: Broad-spectrum agent effective for both focal and generalized seizures; first-line for focal epilepsy but requires slow titration 4, 5
• Lacosamide: Newer agent that enhances slow inactivation of sodium channels; effective as monotherapy for focal seizures 5
• Eslicarbazepine: Third-generation agent related to carbamazepine with improved tolerability profile 5

GABA Enhancers

• Benzodiazepines (diazepam, lorazepam, midazolam): First-line for acute seizures and status epilepticus; act on GABA-A receptors 1, 2
• Phenobarbital: Barbiturate that enhances GABA inhibition; used for refractory status epilepticus but has significant sedative effects 1, 2
• Vigabatrin: Irreversibly inhibits GABA transaminase; used for infantile spasms and refractory focal seizures 5
• Tiagabine: Inhibits GABA reuptake; adjunctive therapy for focal seizures 5

Glutamate Antagonists

• Perampanel: AMPA receptor antagonist; adjunctive therapy for focal and generalized tonic-clonic seizures 5
• Felbamate: NMDA receptor antagonist; reserved for refractory epilepsy due to risk of aplastic anemia and liver failure 5

Multiple Mechanisms

• Valproate: Broad-spectrum agent effective for most seizure types; first-line for generalized epilepsy but has teratogenic potential 1, 2
• Topiramate: Multiple mechanisms including sodium channel blockade and GABA enhancement; effective for focal and generalized seizures 6, 5
• Zonisamide: Blocks sodium channels and T-type calcium channels; broad-spectrum agent 5

Synaptic Vesicle Protein 2A (SV2A) Binders

• Levetiracetam: Binds to SV2A protein; broad-spectrum with minimal drug interactions; first-line option for both focal and generalized seizures 1, 2, 4
• Brivaracetam: Higher affinity for SV2A than levetiracetam; fewer behavioral side effects 5

Memorization Strategies

Group by Mechanism of Action

• Create a mnemonic for sodium channel blockers: "POLE-CL" (Phenytoin, Oxcarbazepine, Lamotrigine, Eslicarbazepine, Carbamazepine, Lacosamide) 3, 4, 5
• GABA enhancers: "BPT-VT" (Benzodiazepines, Phenobarbital, Tiagabine, Vigabatrin, Topiramate) 1, 2, 6

Group by Clinical Use

• Status epilepticus treatment ladder: Benzodiazepines → Phenytoin/Fosphenytoin/Valproate/Levetiracetam → Phenobarbital/Propofol 1, 2
• First-line for focal epilepsy: "LOL" (Lamotrigine, Oxcarbazepine, Levetiracetam) 4, 5
• First-line for generalized epilepsy: "VLT" (Valproate, Lamotrigine, Topiramate) 7, 4

Group by Side Effects

• Enzyme inducers: "CPP" (Carbamazepine, Phenytoin, Phenobarbital) - remember these affect contraceptives and other medications 3
• Cognitive impairment: "TPZ" (Topiramate, Phenobarbital, Zonisamide) 6, 5
• Weight gain: "VCP" (Valproate, Carbamazepine, Pregabalin) 5
• Weight loss: "TZ" (Topiramate, Zonisamide) 6, 5

Treatment Algorithms

Status Epilepticus Management

1. First-line: Benzodiazepines (lorazepam IV, midazolam IM, or diazepam IV/rectal) 1, 2
2. Second-line (if seizures persist after benzodiazepines):
   • Phenytoin/Fosphenytoin: 20 mg/kg IV at max rate of 50 mg/min 1, 2
   • Valproate: 20-30 mg/kg IV over 5-20 minutes (less hypotension than phenytoin) 1, 2
   • Levetiracetam: 30 mg/kg IV over 5 minutes 1, 2
3. Refractory status epilepticus:
   • Midazolam: IV loading dose 0.15-0.20 mg/kg, followed by continuous infusion 2
   • Propofol: 2 mg/kg bolus, followed by 3-7 mg/kg/hour infusion 2
   • Pentobarbital: 13 mg/kg bolus, 2-3 mg/kg/hour infusion 2

Focal Epilepsy Treatment

1. First-line monotherapy: Lamotrigine, Oxcarbazepine, or Levetiracetam 4, 5
2. Alternative monotherapy: Carbamazepine, Topiramate, Zonisamide, or Lacosamide 4, 5
3. Adjunctive therapy (if monotherapy fails): Add a second agent with a different mechanism of action 8

Generalized Epilepsy Treatment

1. First-line: Valproate (avoid in women of childbearing potential), Lamotrigine, or Levetiracetam 7, 4
2. Alternative options: Topiramate, Zonisamide, or Perampanel 5

Key Clinical Pearls

• Approximately 60-70% of patients with epilepsy achieve seizure freedom with appropriate antiseizure medication 7, 4
• Most patients are controlled on a single antiseizure medication; only a small proportion requires combination therapy 8
• When seizures are difficult to control, always reassess the diagnosis of epilepsy and medication adherence 8
• Antiseizure medications with enzyme-inducing properties (carbamazepine, phenytoin, phenobarbital) can worsen comorbid conditions and interact with many medications 3, 4
• Prophylactic antiseizure medications are not recommended for patients with brain metastases who have not had seizures 1
• For patients with epilepsy who develop status epilepticus, loading doses of their regular medications can be administered with minimal toxicity 9

By organizing antiseizure medications by mechanism, clinical use, and side effects, you'll be well-prepared for Step 1 questions on this topic.