First-Line Treatment for Seizures
For acute seizures, immediately administer intravenous lorazepam 4 mg at 2 mg/min; for chronic therapy after a first unprovoked seizure, initiate levetiracetam or lamotrigine as first-line agents, with valproate reserved for generalized seizures in patients who are not of childbearing potential. 1, 2, 3
Acute Emergency Management
Immediate First-Line Treatment (0-5 minutes)
Benzodiazepines are the only appropriate first-line agents for any actively seizing patient. 1, 2, 4
Intravenous lorazepam 4 mg at 2 mg/min is the preferred agent when IV access is available, terminating status epilepticus in 65% of cases and demonstrating superior efficacy to diazepam (59.1% vs 42.6% seizure cessation). 1, 2, 4
Intramuscular midazolam is equally effective when IV access is unavailable or delayed, particularly valuable in prehospital settings. 2
Intranasal or buccal midazolam are acceptable alternatives showing 88-93% efficacy in stopping seizures within 10 minutes. 2
Critical safety measure: Have airway equipment (bag-valve-mask, intubation set) immediately available before administering any benzodiazepine, as respiratory depression requiring intervention is predictable. 1, 2, 4, 5
Concurrent action: Check fingerstick glucose immediately and correct hypoglycemia while administering the benzodiazepine—this is a rapidly reversible cause that must not be missed. 1, 2
Why Benzodiazepines Must Be First
The evidence is unequivocal: a short window of opportunity exists when seizures are maximally controlled by benzodiazepines. After minutes to an hour, GABA-A receptor alterations develop that create benzodiazepine pharmacoresistance and self-sustaining status epilepticus. 5 Delaying benzodiazepine administration to give phenytoin, levetiracetam, or any other agent first is never appropriate and increases morbidity and mortality. 1, 2
Second-Line Treatment (5-20 minutes)
If seizures persist after adequate benzodiazepine dosing, immediately escalate to one of these agents—do not delay. 1, 2, 3
Valproate 20-30 mg/kg IV over 5-20 minutes (maximum 3000 mg) is the safest second-line option, achieving 88% seizure cessation with 0% hypotension risk. 1, 2, 3 However, it is absolutely contraindicated in women of childbearing potential due to fetal teratogenic risk. 1
Levetiracetam 30 mg/kg IV over 5 minutes (maximum 2500-3000 mg) produces 68-73% seizure cessation with minimal cardiovascular effects (≈0.7% hypotension risk, 20% intubation rate) and requires no cardiac monitoring. 1, 2, 3
Fosphenytoin 20 mg PE/kg IV at ≤150 PE/min achieves 84% seizure cessation but carries 12% hypotension risk and 26.4% intubation rate, necessitating continuous ECG and blood pressure monitoring. 1, 2, 3
Phenobarbital 20 mg/kg IV over 10 minutes yields only 58.2% seizure cessation as an initial second-line agent and carries higher risks of respiratory depression and hypotension—it should not be used as first-line treatment. 1, 2, 6
Refractory Status Epilepticus (20+ minutes)
Midazolam continuous infusion (loading dose 0.15-0.20 mg/kg IV; maintenance 1 mg/kg/min titrated up to 5 mg/kg/min) is the preferred anesthetic agent, achieving 80% seizure termination with ≈30% hypotension risk. 1, 3 Crucially, load a long-acting anticonvulsant (phenytoin/fosphenytoin, valproate, or levetiracetam) before tapering the midazolam infusion to ensure adequate anticonvulsant coverage. 1
Propofol (bolus 2 mg/kg; infusion 3-7 mg/kg/h) yields 73% seizure control with ≈42% hypotension but requires mechanical ventilation for a shorter duration than barbiturates (4 vs 14 days). 1, 3
Pentobarbital (bolus 13 mg/kg; infusion 2-3 mg/kg/h) has the highest efficacy at 92% but carries 77% hypotension risk requiring vasopressors and prolonged ventilation (mean 14 days). 1
Essential Concurrent Actions
While administering anticonvulsants, simultaneously search for and treat reversible causes: hypoglycemia, hyponatremia, hypoxia, drug toxicity or withdrawal, CNS infection, ischemic stroke, or intracerebral hemorrhage. 1, 2, 3 Do not postpone anticonvulsant therapy to obtain neuroimaging. 1
Chronic Seizure Therapy After First Unprovoked Seizure
When to Initiate Chronic Therapy
Treatment of the first unprovoked seizure should be considered in patients with:
- Abnormal EEG findings (predicts higher recurrence risk) 7
- Abnormal neuroimaging findings 7
- Severe social, emotional, or personal implications of seizure relapse 7
First-Line Chronic Anticonvulsants
For generalized tonic-clonic seizures: Sodium valproate is first-line, with lamotrigine and levetiracetam as suitable alternatives. 3, 7 Avoid valproate in women of childbearing potential—use levetiracetam or lamotrigine instead. 3, 7
For complex partial seizures: Carbamazepine, oxcarbazepine, lamotrigine, and levetiracetam are first-line options. 3, 7
Specific population guidance:
- Children: Oxcarbazepine for partial seizures 7
- Adults: Carbamazepine or lamotrigine for partial seizures 7
- Elderly: Lamotrigine or gabapentin for partial seizures 7
- End-stage renal disease: Levetiracetam is superior due to predictable dialysis dosing adjustments 3
Critical Pitfalls in Chronic Management
- Never abruptly discontinue antiepileptic drugs—this risks precipitating status epilepticus. 3
- Avoid enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital) due to significant drug interactions and side effects. 3
- Check HLA-B*1502 in Asian patients before starting carbamazepine due to Stevens-Johnson syndrome risk. 3
- Monitor for thrombocytopenia with valproate. 3
- Start with the lowest effective maintenance dose based on efficacy and tolerability. 7