Seizures and Anti-Seizure Medicines: The Evidence Behind the Pathway

A 26-year-old woman is carried into casualty by her husband. She has been convulsing for ten minutes, and she has not woken between the jerks. She has had epilepsy since school and ran out of her tablets last week. She weighs 55 kg. The nurse has a cannula in. This is an illustrative case, not a real patient.

By the end of this article you will know what to give her in the first minutes, how to choose the second drug and load it safely, and why the way a drug works is not the way we choose it.

1. Stop the Convulsion First

The tool opens its Evidence tab with one instruction: stop the convulsion first. Prolonged seizure activity injures neurons in a way that does not recover, and the body’s metabolism collapses alongside it. Neither waits for a diagnosis. So work out the cause while the drugs are going in, not before.

“Then I give the benzodiazepine straight away?” Almost. First, check the glucometer random blood sugar (GRBS). Hypoglycaemia both mimics and provokes status epilepticus, and it takes a minute to exclude. If the GRBS is under 60 mg/dL, give 100 mL of 25% dextrose IV. Where nutrition is poor, 100 mg of thiamine goes in first, to prevent Wernicke’s encephalopathy.

Her GRBS is 96 mg/dL. The tool’s first step is lorazepam, 0.1 mg/kg IV, maximum 4 mg. At 55 kg that would be 5.5 mg, so she gets the maximum, 4 mg, over 1 to 2 minutes. It is repeated once after 5 minutes if she is still convulsing. Without a cannula, the route is intramuscular midazolam.

2. The Second Drug

Five minutes after the second dose of lorazepam, she is still jerking. This is established status epilepticus, and she needs a loading dose of a second drug. The tool offers three: levetiracetam, sodium valproate and phenytoin. The ESETT trial compared levetiracetam, valproate and fosphenytoin (a form of phenytoin made to be given faster) head to head, in adults and in children. About half of the patients stopped seizing with each, and none of the three was clearly better than the others.

“So I can pick any of the three?” Not for her. She is a woman of childbearing potential, and the tool’s advisory is plain: do not give sodium valproate to a female of childbearing potential. Of all the anti-seizure medicines (ASMs) used in pregnancy, it carries the highest rate of major congenital malformation and of neurodevelopmental delay. Only two situations override this: refractory status epilepticus, and a myoclonic syndrome where every alternative has already failed.

That leaves levetiracetam or phenytoin. Levetiracetam is 60 mg/kg, maximum 4500 mg: for her, 3300 mg. Phenytoin is 20 mg/kg, maximum 1500 mg: for her, 1100 mg.

“Phenytoin is what we always used. Why is it the harder one?” Because of how it must be given. The tool keeps the rules in red. Dilute it only in 0.9% normal saline, never in dextrose, which precipitates it at once. Use an inline filter. Do not exceed 50 mg/min in an adult, and watch the ECG and the blood pressure for the whole of the load. Her 1100 mg therefore takes at least 22 minutes. The reason for the rate limit is the vehicle: phenytoin comes dissolved in propylene glycol at an alkaline pH, and given faster it causes severe myocardial depression, bradyarrhythmias, QT prolongation and life-threatening hypotension.

3. How Each Drug Works

The tool used to carry a column on how each drug works. Here is its drug table as one. As you read it, notice how many lines say the same thing in the middle column:

A few words first. A neuron fires when sodium channels in its membrane open. Sodium channel blockers (phenytoin, carbamazepine, oxcarbazepine, lamotrigine, and lacosamide in its own way) make a neuron less able to fire again and again. GABA is the brain’s main calming chemical messenger; the benzodiazepines strengthen its receptor, and valproate acts partly through it. SV2A is a protein on the small sacs that release chemical messengers at the nerve ending, and levetiracetam binds to it. T-type calcium channels in the thalamus help drive the rhythm of an absence seizure, which is why ethosuximide, which blocks them, is so narrow in what it treats.

“Then should I choose by mechanism?” No, and this is worth holding on to. A mechanism tells you how a drug works. It does not tell you whether it works better. Three of the eight lines carry the same words, two more name the sodium channel too, and yet these drugs behave very differently at the bedside. Look at the right-hand column instead, which is what the tool keeps. Levetiracetam has no hepatic drug interactions, and that comes from how it leaves the body, through the kidney, not from SV2A. Phenytoin’s zero-order kinetics mean that a tiny dose increase can cause profound toxicity. Lamotrigine must be titrated slowly, because a fast escalation is what precipitates Stevens-Johnson syndrome. Lacosamide prolongs the PR interval. Carbamazepine induces its own metabolism and can lower the sodium. Those are the facts that change what you do.

4. When She Does Not Wake

The convulsions stop halfway through the levetiracetam. Twenty minutes later she has still not woken. The tool is clear: if a patient has not regained consciousness 20 minutes after the motor convulsions stop, assume non-convulsive status epilepticus (NCSE) until an EEG says otherwise, and get that EEG emergently. Check the sodium too. A serum sodium under 120 mEq/L is a potent seizure trigger, and if she convulses with it, 100 mL of 3% hypertonic saline IV over 10 to 15 minutes is the treatment.

5. The Common Mistake

The common mistake is to wait. We wait for the cannula when intramuscular midazolam would do, for the CT before the second drug, for the senior before the load. It is easy to see why: we want to know what we are treating. But the tool’s first sentence is the answer. Every minute of seizure costs neurons, and the cause can be found while the drugs are going in. The second mistake is the phenytoin drip in dextrose, run fast because the patient is still jerking.

Back to Our Patient

She got 4 mg of lorazepam twice, then 3300 mg of levetiracetam. When she did not wake, an EEG was arranged at once. Her sodium was normal. For maintenance she goes back to an ASM that is safe if she becomes pregnant, levetiracetam or lamotrigine, not valproate. And someone sits down with her and her husband to make sure the tablets do not run out again.

Try This

A 45-year-old man who drinks heavily has a generalised seizure 18 hours after his last drink. He has no history of epilepsy. Should he be loaded with phenytoin? Illustrative case.

Answer. No. Alcohol withdrawal seizures occur 6 to 48 hours after the last drink, peaking at 12 to 24 hours, and they arise from a transient receptor imbalance rather than an epileptic focus. Randomised trials have shown that phenytoin does not prevent their recurrence. Benzodiazepines are both the treatment and the prophylaxis, with thiamine cover. A first-ever seizure still needs its own evaluation. The alcohol withdrawal article has the regimen.

Take-Home Points

• Stop the convulsion first; check the GRBS, then lorazepam 0.1 mg/kg IV, maximum 4 mg, repeated once after 5 minutes.
• For the second drug, levetiracetam, valproate and fosphenytoin did about equally well in ESETT; choose by the patient.
• Do not give sodium valproate to a female of childbearing potential, outside the two stated exceptions.
• Phenytoin goes in 0.9% saline only, through a filter, at no more than 50 mg/min, with the ECG and blood pressure watched.
• Not awake 20 minutes after the convulsions stop: assume NCSE and get an EEG emergently.

For seizures after a head injury, see Head Injury: The Evidence Behind the Pathway; for a low sodium, Acute Hyponatraemia.

Declaration: the author built and maintains the tool. It is free to use. The figures in this article are those the tool carried in its Evidence tab on 5 November 2026, each from the source the tool names; the ESETT finding is from the trial reports in the reference list (references 2 and 7). The illustrative cases follow the tool’s rules; check the tool’s result for a real patient.

References

1. Glauser T, et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48-61. PMID 26900382.
2. Kapur J, Elm J, Chamberlain JM, et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus (ESETT). N Engl J Med. 2019;381(22):2103-2113. PMID 31774955.
3. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocritical Care Society. Neurocrit Care. 2012;17(1):3-23. PMID 22528274.
4. Ramaratnam S, Satishchandra P. Guidelines for epilepsy management in India. Ann Indian Acad Neurol. 2010;13(4):247-249. PMID 21264131.
5. Trinka E, et al. A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56(10):1515-1523. PMID 26336950.
6. Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus (RAMPART). N Engl J Med. 2012;366(7):591-600. PMID 22335736.
7. Chamberlain JM, Kapur J, Shinnar S, et al. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial. Lancet. 2020;395(10231):1217-1224. PMID 32203691.
8. Marson A, Burnside G, Appleton R, et al. The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy. Lancet. 2021;397(10282):1363-1374. PMID 33838757.
9. Marson A, Burnside G, Appleton R, et al. The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy. Lancet. 2021;397(10282):1375-1386. PMID 33838758.
10. Nair PP, Kalita J, Misra UK. Status epilepticus: why, what, and how. J Postgrad Med. 2011;57(3):242-252. PMID 21941070.