What are the drugs of choice for different types of seizures, including partial onset seizures, myoclonic seizures, primary generalized tonic-clonic seizures, and status epilepticus, in patients with varying medical histories, ages, and renal function?

Drug of Choice for Each Type of Seizure

Partial Onset Seizures

Carbamazepine should be preferentially offered to children and adults with partial onset seizures as first-line monotherapy. 1

• Standard antiepileptic drugs for partial seizures include carbamazepine, phenobarbital, phenytoin, and valproic acid, all offered as monotherapy 1
• Levetiracetam is approved as adjunctive therapy for partial-onset seizures in adults and children, with 15% of patients on 1000 mg/day and 20-30% on 3000 mg/day achieving ≥50% seizure reduction 2, 3
• Topiramate is indicated as adjunctive therapy for partial onset seizures in adults and pediatric patients ages 2-16 years, and as initial monotherapy in patients ≥10 years 4
• In resource-limited settings, phenobarbital should be offered as first option given acquisition costs, if availability can be assured 1

Primary Generalized Tonic-Clonic Seizures

Valproic acid is the first-choice treatment for primary generalized tonic-clonic seizures in males and menopausal women without weight concerns. 5

• Valproic acid, lamotrigine, levetiracetam, topiramate, and perampanel are all effective options for primary generalized tonic-clonic seizures 5
• Lamotrigine and levetiracetam serve as viable alternatives to valproic acid as first-choice agents 5
• Topiramate is effective as first choice but carries concerns regarding cognitive and memory adverse effects 5
• Topiramate is indicated as initial monotherapy for primary generalized tonic-clonic seizures in patients ≥10 years 4
• Valproic acid should be avoided in women of childbearing potential due to significantly increased risks of fetal malformations and neurodevelopmental delay 1

Myoclonic Seizures

Levetiracetam is indicated as adjunctive therapy for myoclonic seizures in patients with idiopathic generalized epilepsy. 3

• Valproic acid remains an effective option for myoclonic seizures when not contraindicated 1
• The drug choice depends on the specific type of seizure and should account for patient age, gender, and comorbidities 5

Status Epilepticus

First-Line Treatment

IV lorazepam 4 mg at 2 mg/min should be administered immediately as first-line treatment for any actively seizing patient, with 65% efficacy in terminating status epilepticus. 6

• Benzodiazepines represent Level A (strongest) first-line treatment, with lorazepam demonstrating superior efficacy over diazepam (59.1% vs 42.6%) 6
• IM midazolam or intranasal midazolam are alternatives when IV access is unavailable 6
• Rectal diazepam should be administered when IV access is not available; IM diazepam is not recommended due to erratic absorption 1
• Have airway equipment immediately available before administering lorazepam due to respiratory depression risk 6

Second-Line Treatment (Benzodiazepine-Refractory)

Valproate 20-30 mg/kg IV over 5-20 minutes should be administered as the preferred second-line agent, with 88% efficacy and 0% hypotension risk. 6

• Valproate demonstrates superior safety profile compared to phenytoin/fosphenytoin (88% efficacy with 0% hypotension vs 84% efficacy with 12% hypotension) 6
• Levetiracetam 30 mg/kg IV over 5 minutes is an excellent alternative with 68-73% efficacy and minimal cardiovascular effects 6, 7
• Fosphenytoin 20 mg PE/kg IV at maximum 50 mg/min is the traditional second-line agent with 84% efficacy but requires continuous ECG and blood pressure monitoring 6
• Phenobarbital 20 mg/kg IV over 10 minutes has 58.2% efficacy but carries higher risk of respiratory depression 6
• Never skip directly to third-line agents until benzodiazepines and a second-line agent have been tried 6

Refractory Status Epilepticus (Third-Line)

Midazolam infusion should be initiated as first-choice anesthetic agent for refractory status epilepticus, with 0.15-0.20 mg/kg IV loading dose followed by 1 mg/kg/min continuous infusion. 6

• Midazolam demonstrates 80% overall success rate with 30% hypotension risk, superior safety profile compared to pentobarbital (77% hypotension) 6
• Propofol 2 mg/kg bolus followed by 3-7 mg/kg/hour infusion achieves 73% seizure control with 42% hypotension risk and requires mechanical ventilation 6
• Pentobarbital 13 mg/kg bolus followed by 2-3 mg/kg/hour infusion has highest efficacy at 92% but 77% hypotension risk requiring vasopressors and prolonged ventilation (mean 14 days) 6
• Continuous EEG monitoring is essential at this stage to guide titration and detect ongoing electrical seizure activity 6
• Load with phenytoin/fosphenytoin, valproate, levetiracetam, or phenobarbital during the anesthetic infusion to ensure adequate long-acting anticonvulsant levels before tapering 6

Special Populations

Women of Childbearing Potential

Seizures should be controlled with antiepileptic drug monotherapy at minimum effective dose, avoiding valproic acid and polytherapy. 1

• Folic acid should routinely be taken when on antiepileptic drugs 1
• Standard breastfeeding recommendations remain appropriate for phenobarbital, phenytoin, carbamazepine, and valproic acid 1

Patients with Intellectual Disability

Consider valproic acid or carbamazepine instead of phenytoin or phenobarbital due to lower risk of behavioral adverse effects. 1

• Drug choice depends on seizure type and should be individualized 1
• These patients should have access to the same range of investigations and treatment as the general population 1

Febrile Seizures

Follow local standards for diagnosis and management of fever; children with simple febrile seizures should be observed for 24 hours without prophylactic anticonvulsants. 1

• Children with complex febrile seizures should be observed in an inpatient setting with appropriate investigations 1
• Prophylactic intermittent diazepam during febrile illness may be considered for recurrent or prolonged complex febrile seizures, but not for simple febrile seizures 1

Critical Monitoring and Management Principles

• Antiepileptic drugs should not be routinely prescribed after a first unprovoked seizure 1
• Discontinuation of antiepileptic drug treatment should be considered after 2 seizure-free years, with decision made after consideration of clinical, social, and personal factors 1
• Simultaneously search for and treat underlying causes during status epilepticus management, including hypoglycemia, hyponatremia, hypoxia, drug toxicity, CNS infection, stroke, and withdrawal syndromes 6
• Continuous vital sign monitoring is essential, particularly respiratory status and blood pressure, with preparation to provide respiratory support 6