Seizures and Epilepsy

Epilepsy is a neurological disease characterized by an enduring predisposition to generate unprovoked seizures — practically defined by the International League Against Epilepsy (ILAE) as 2 unprovoked seizures more than 24 hours apart, 1 unprovoked seizure with a high (over 60%) probability of recurrence over the next 10 years, or diagnosis of a recognized epilepsy syndrome.^[1] A seizure itself is classified as focal if it originates in one cerebral hemisphere or generalized if it engages both hemispheres simultaneously — this single distinction is the primary driver of antiseizure medication (ASM) selection, since several first-line agents differ by seizure type and some agents that work well for one type can worsen another.^[2] Managing epilepsy addresses not only seizure prevention but the biological, cognitive, psychological, and social consequences of the disease, and — separate from chronic epilepsy management — status epilepticus is a distinct, time-critical emergency requiring immediate benzodiazepine treatment regardless of whether the underlying cause is known epilepsy or a new provoked seizure.

Seizure semiology — what the seizure actually looks like — is the foundation of both diagnosis and drug selection. The single most important classification is whether a seizure is focal (originates in one hemisphere) or generalized (engages both hemispheres simultaneously), because this determines which first-line antiseizure medications are appropriate and which agents can actually worsen seizure control if the seizure type is misclassified.^[2]

Status epilepticus — any seizure that fails to self-terminate — is covered separately below (Red Flags and Refer, Choose Initial Treatment, and the Clinical Decision Algorithm), since it requires immediate emergency management rather than routine outpatient ASM selection.

Risk factors for seizures and epilepsy

• Family history of seizures or other neurologic disease.
• History of recurrent or prolonged seizures in childhood, intracranial infection, head trauma, stroke, or any systemic disorder affecting the CNS.
• Known structural brain abnormality (prior stroke, traumatic brain injury, tumor, cortical malformation).
• A recognized genetic epilepsy syndrome (e.g., childhood absence epilepsy, juvenile myoclonic epilepsy).
• Developmental abnormalities or intellectual disability with childhood-onset epilepsy.

Precipitants of an isolated (provoked) seizure

• Use of prescribed or recreational drugs, or alcohol intoxication or withdrawal.
• Toxic or metabolic derangement from an acute medical illness (e.g., hypoglycemia, hyponatremia).
• An acute brain insult — traumatic brain injury, stroke, or encephalitis — within the preceding 7 days.

Precipitants of breakthrough seizure in known epilepsy

• Medication nonadherence — the most common cause of seizure breakthrough in patients with known epilepsy.
• Intercurrent illness with fever or vomiting.
• Sleep deprivation.
• Alcohol or nonprescription drug use.
• Pregnancy (via pharmacokinetic changes — see Special Populations).
• Addition or withdrawal of a drug that affects seizure threshold or interacts with antiseizure medications.
• Sudden withdrawal from alcohol, benzodiazepines, or barbiturates.

Differentiating epileptic seizures from common mimics

History

• Obtain a detailed description of the "spell" from both the patient and a witness — this is the single most important step in diagnosis.
• Ask specifically about an aura (e.g., a rising abdominal sensation, sudden fear, déjà vu) — its presence indicates focal seizure onset and its character can localize the seizure focus; its absence may reflect a generalized seizure, or a focal seizure that spread too rapidly to produce a recognized aura.
• Ask about prior recurrent or prolonged childhood seizures, intracranial infection, head trauma, stroke, other CNS-affecting systemic disease, and family history of seizures or neurologic disease.
• Establish whether a precipitant of an isolated provoked seizure occurred within the preceding 7 days (see Risk Factors).
• In a patient with known epilepsy presenting with seizure recurrence, specifically ask about adherence, intercurrent illness, sleep deprivation, alcohol/substance use, pregnancy, and any recent medication change (see Risk Factors) — nonadherence is the most common identifiable cause.

Physical examination

• Look for evidence of a systemic disorder affecting the CNS (malignancy, infection, autoimmune disease, a drug toxidrome or withdrawal syndrome).
• Look for focal or lateralizing neurologic findings — hemianopia, motor weakness, hemisensory disturbance, reflex asymmetry, language dysfunction.
• Assess for injury sustained during a generalized tonic-clonic seizure — tongue laceration, shoulder dislocation, vertebral compression fracture, burns, or other trauma.

Investigations

First seizure: obtain CBC, glucose, electrolytes, calcium, and renal/hepatic function; add an alcohol level, toxicology screen, and infection screen (urinalysis/culture, especially in older or developmentally challenged patients) when a provoked cause is plausible; obtain a chest x-ray if metastatic disease is a consideration and an ECG to exclude a significant cardiac conduction abnormality.^[4]

Obtain an EEG to support the clinical impression of a seizure and to help determine focal versus generalized onset — an interictal EEG may show focal spikes or generalized spike-wave discharges and can help estimate recurrence risk. A normal EEG does not rule out epilepsy or future seizure risk.

Obtain a brain MRI (preferred) in essentially all patients with an unprovoked seizure, unless there is a clear diagnosis of a generalized epilepsy syndrome (e.g., childhood absence epilepsy, juvenile myoclonic epilepsy) or an already-known structural cause. CT can be used in the acute/urgent setting, or when MRI is unavailable or contraindicated.

Obtain a lumbar puncture when the presentation suggests intracranial infection (meningitis, encephalitis) or a CT-negative subarachnoid hemorrhage — it is not routinely indicated for an uncomplicated first seizure without these features.

For a patient with known epilepsy presenting with seizure recurrence, check an ASM serum level where clinically useful — phenytoin, phenobarbital, primidone, carbamazepine, and valproic acid have established, interpretable serum levels. Levels for most other ASMs are difficult to obtain and of limited clinical value, so do not order them as a routine reflex.

• Appropriately decide whether antiseizure medication (ASM) therapy is indicated after a first seizure.
• Prevent or minimize seizure recurrence and severity in patients with an established diagnosis of epilepsy.
• Achieve seizure freedom on ASM monotherapy whenever possible before considering polytherapy.
• Prevent or minimize ASM adverse effects, including long-term risks (osteoporosis, teratogenicity, cognitive effects).
• Optimize quality of life — employment, psychosocial functioning, and driving eligibility.
• In status epilepticus, terminate seizure activity as rapidly as possible to limit neuronal injury and systemic complications.

Lifestyle and general measures

• Encourage adequate sleep — sleep deprivation lowers the seizure threshold in some patients.
• Advise minimal alcohol intake; cocaine and amphetamines must be avoided given their proconvulsant properties.
• Ask specifically about herbal remedies and dietary supplements, since some carry proconvulsant properties or clinically important ASM interactions.
• A ketogenic, modified Atkins, or low-glycemic-index diet can reduce seizure frequency in selected patients, though a strict ketogenic diet is impractical for most adults; involve a dietitian given the risk of nutritional deficiency and diet-ASM interactions.
• Cannabidiol oral solution is Health Canada-approved specifically as adjunctive therapy for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex — it is not a general-purpose antiseizure treatment, and evidence for recreational cannabis as a seizure treatment remains inconclusive.
• Complementary practices such as yoga and mindfulness-based therapy have some evidence for improving quality of life, mood, and possibly seizure control; meditation, relaxation training, and acupuncture have more limited evidence but low risk, and can be considered for overall wellbeing.

General safety measures and seizure precautions

• People with epilepsy have a higher risk of death from unintentional injury or poisoning than the general population and should be counselled accordingly.
• To reduce burn risk: discourage smoking, and encourage using a microwave and the rear burners of a stove.
• Avoid heights, ladders, and power tools.
• Prefer showers over baths, given drowning risk.
• Assess recreational activities and current/planned employment for environmental hazards, and counsel accordingly.
• Patients with active epilepsy who care for young children should not bathe them unassisted and should not use a change table for diapering.
• Consider referral to an epilepsy support group.

Driving

Assess driving status at every visit after a seizure. Under the current Canadian Medical Association / Canadian Council of Motor Transport Administrators standard, a non-commercial licence generally requires being seizure-free for at least 6 months under ongoing medical care (or a consistent sleep-only/on-waking seizure pattern sustained for at least 12 months); a commercial licence generally requires 5 years seizure-free, occasionally reduced to 3 years for specific epilepsy types on a neurologist's recommendation.^[6] Reporting obligations to provincial licensing authorities differ by province (mandatory physician reporting versus patient self-reporting) — reinforce that the patient, not only the prescriber, has a personal obligation to stop driving after any seizure and to understand their own province's specific rule.

Epilepsy surgery and neuromodulation

Refer for consideration of epilepsy surgery and/or neuromodulation when seizures remain medically refractory despite 2 or more appropriately selected and dosed ASM trials — this does not include an ASM that was discontinued solely for adverse effects rather than lack of efficacy.

Pregnancy

Prepregnancy: reassess whether ongoing ASM treatment is still needed, and — if ASM polytherapy includes valproate or topiramate — consider withdrawing whichever agent contributed least to seizure control, since polytherapy that includes either drug raises congenital-malformation risk above monotherapy. Teratogenic risk is dose-dependent for every ASM but is particularly pronounced for valproate and topiramate; avoid valproic acid in patients of childbearing potential where possible, weighed against the real risk of uncontrolled seizures.

Folic acid: every patient of childbearing potential taking an ASM falls into the moderate-risk category and should receive 1 mg folic acid PO daily; reserve the high-risk 4-5 mg PO daily dose for a personal or family history of neural tube defect. Start at least 3 months before conception and continue until 12 weeks' gestational age; from 12 weeks through the rest of pregnancy and for 4-6 weeks postpartum (or as long as breastfeeding continues), continue a multivitamin with 0.4-1 mg folic acid daily.^[7]

During pregnancy: lamotrigine and levetiracetam have the most reassuring safety data among commonly used ASMs and are reasonable first choices. Valproic acid should be avoided where possible given its established association with major congenital malformations and adverse neurodevelopmental outcomes; in a large registry-based active-comparator analysis, this elevated neurodevelopmental risk persisted for valproate after adjusting for confounding by indication, while topiramate and lamotrigine did not show a comparable increased risk once analyzed the same way — reinforcing that valproate, not topiramate, carries the highest neurodevelopmental risk among the commonly used ASMs.^[8] Phenobarbital is associated with increased congenital cardiac malformation risk, topiramate with cleft lip/palate and other malformations, and phenytoin/carbamazepine with an increased major-malformation risk generally.

Do not switch ASM during pregnancy to try to "avoid" teratogenicity — the period of highest malformation risk (the first trimester) has often already passed by the time pregnancy is recognized, and a mid-pregnancy switch exposes the fetus to polytherapy risk while exposing the patient to new-drug hypersensitivity risk and a real risk of breakthrough seizures or status epilepticus.

Level monitoring during pregnancy: obtain serial ASM levels when available and feasible; consider a dose adjustment if a level falls more than 25% below a documented prepregnancy reference level. Lamotrigine, levetiracetam, oxcarbazepine, topiramate, and lacosamide levels can all fall substantially during pregnancy from increased volume of distribution and clearance — lamotrigine is the most dramatic example and often needs its dose doubled or more, checked at least monthly; levels then rise quickly after delivery, so the dose must be tapered back down promptly postpartum (over the first 1-2 weeks) to avoid toxicity.

Breastfeeding

Breastfeeding should not be discouraged — while many ASMs transfer into breast milk, milk concentrations are generally well below maternal serum concentrations. Monitor the infant for sedation, poor feeding, or lethargy when the mother takes a barbiturate, a benzodiazepine, ethosuximide, or lamotrigine, since these are the agents most likely to sedate a breastfed infant; infants exposed to barbiturates or benzodiazepines in utero who are not breastfed may show withdrawal symptoms in the first week after delivery.

Reproductive-age patients: contraception and enzyme-inducing ASMs

This is one of the most consequential drug-interaction issues in epilepsy pharmacotherapy — an interaction missed at counselling can directly lead to an unplanned pregnancy while on a teratogenic ASM.

Combined oral contraceptives, the contraceptive patch, the vaginal ring, the progestin-only pill, and some progestin implants are all less effective when combined with an enzyme-inducing ASM. Preferentially recommend an intrauterine device (hormonal or nonhormonal) or a depot progesterone injection, since these are not significantly affected by enzyme induction; encourage condom use alongside any hormonal method both for a second layer of contraceptive protection and for STI prevention.^[9] If a patient specifically prefers to continue a combined oral contraceptive despite enzyme-inducer use, some experts support using 2 tablets/day of a low-dose product to approximate a higher ethinyl estradiol exposure, always with a reliable backup barrier method, since no single-tablet Canadian product reaches an equivalent dose on its own.^[10]

The lamotrigine-specific interaction runs the other direction: combined hormonal contraceptives induce lamotrigine glucuronidation and can substantially lower lamotrigine serum levels, risking breakthrough seizures. Check a lamotrigine level before and after starting a combined hormonal contraceptive, and expect to need a meaningfully higher lamotrigine dose while the contraceptive is used — with a corresponding dose reduction if the contraceptive is later stopped, to avoid lamotrigine toxicity.

Older adults

Start ASMs at a lower initial dose and titrate more slowly, given increased sensitivity to sedation, cognitive effects, and falls risk. Favour agents with fewer drug interactions (levetiracetam, lamotrigine, gabapentin) given the high burden of concurrent medications in this population, and reduce doses of renally cleared agents (e.g., levetiracetam, gabapentin) for reduced creatinine clearance.

Renal and hepatic impairment

Renally cleared ASMs (levetiracetam, gabapentin, vigabatrin, and others — see Drug Tables) require dose reduction as creatinine clearance falls. Hepatically metabolized ASMs with enzyme-inhibiting or enzyme-inducing properties (valproic acid, carbamazepine, phenytoin, phenobarbital) need caution, and for some, dose adjustment, in significant hepatic impairment; valproic acid in particular carries a rare but serious hepatotoxicity risk that warrants closer monitoring in any degree of pre-existing hepatic disease.

Pediatrics

This chapter focuses on adult epilepsy management. Pediatric-specific considerations — including that childhood absence epilepsy is generally treated first-line with ethosuximide rather than the adult generalized-epilepsy approach, and that several agents in the Drug Tables below (e.g., rufinamide, stiripentol) are specifically pediatric-onset-syndrome indications — should be managed with pediatric neurology/epilepsy specialist input rather than extrapolated directly from adult dosing.

Therapeutic drug monitoring

Do not rely on a serum ASM level alone to guide therapy — treat the patient, not the level. Some patients achieve seizure control at a low level; others experience dose-related toxicity within the so-called therapeutic range. A useful practice is to obtain a level when the patient is seizure-free and free of dose-related toxicity, to serve as a personal reference point if seizures or toxicity occur later. Routine levels are most useful for phenytoin, phenobarbital, primidone, carbamazepine, and valproic acid; levels for most newer ASMs are harder to obtain and rarely change management, so do not order them reflexively.

Baseline and periodic monitoring

• Obtain a baseline CBC and liver aminotransferases before starting an ASM with hypersensitivity, blood-dyscrasia, or hepatotoxicity potential (e.g., carbamazepine, valproic acid); repeat at 4-6 weeks, then space out the interval if results remain stable — yearly is appropriate once stable.
• Test for HLA-B*15:02 before starting carbamazepine in patients with ancestry from a country with higher carrier prevalence (China, Thailand, Malaysia, India) given the sharply increased Stevens-Johnson syndrome/toxic epidermal necrolysis risk in carriers.
• Monitor bone density per standard osteoporosis guidance in patients on long-term valproic acid or an enzyme-inducing ASM, and consider calcium/vitamin D supplementation.
• Reassess adherence at every visit — it is the most common identifiable cause of breakthrough seizures.
• Reassess driving eligibility, mood/psychiatric symptoms, and quality of life at every visit, not only seizure frequency.
• Switching between brand and generic, or between different generic products, has not been shown to harm most low-risk patients — but a minority may be sensitive to small formulation changes and warrant extra caution, particularly with lamotrigine given its narrow hypersensitivity-related titration window.

Discontinuing antiseizure medication

ASM withdrawal can be considered in selected patients after a substantial, sustained period of seizure freedom, always in consultation with a neurologist or epilepsy specialist — this decision carries real implications for driving, personal safety, and psychological wellbeing, and even prolonged seizure freedom does not eliminate recurrence risk with withdrawal. The long-term risk of seizure recurrence is higher for patients who taper their ASM after 2 years of seizure freedom compared with those who continue therapy, so the decision to taper should weigh this against the burdens of continued long-term treatment on a genuinely individualized basis.^[11]

1. Confirm the diagnosis is genuinely epileptic seizures — reconsider syncope, psychogenic nonepileptic seizures, and other mimics (see Assessment and Diagnosis) before escalating ASM therapy for apparent "drug failure."
2. Confirm adherence and correct dosing, and check a serum level where clinically useful (phenytoin, phenobarbital, primidone, carbamazepine, valproic acid) — nonadherence is the most common cause of apparent treatment failure.
3. Optimize the current ASM to its maximum tolerated dose before concluding it has failed.
4. If the maximum tolerated dose of the first ASM has genuinely failed, add a second agent selected by seizure type and interaction profile, then gradually withdraw the first once the second reaches its maintenance dose — true polytherapy is reserved for patients who have failed 2-3 appropriately selected and dosed monotherapy trials.
5. Reassess for reversible precipitants at every apparent failure — sleep deprivation, alcohol, an interacting new medication, or (in patients of reproductive potential) pregnancy-related pharmacokinetic changes.
6. Refer to a tertiary epilepsy centre for further evaluation, including consideration of epilepsy surgery or neuromodulation, once seizures remain uncontrolled despite adequate trials of 2-3 ASMs.
7. For status epilepticus specifically, escalate strictly along the benzodiazepine, second-line IV load, refractory-status pathway (see Choose Initial Treatment) rather than repeating a step that has already failed.

• Relying on a serum ASM level alone to guide dosing instead of the patient's actual seizure control and tolerability.
• Missing the enzyme-inducing-ASM/hormonal-contraception interaction — a preventable cause of unplanned pregnancy on a teratogenic drug.
• Starting valproic acid or topiramate first-line in a patient of childbearing potential without first discussing lower-risk alternatives.
• Continuing an ASM after a definite drug rash develops, risking a life-threatening hypersensitivity reaction.
• Titrating lamotrigine faster than the recommended slow schedule, even when the patient wants faster seizure control.
• Using an oral, rather than parenteral/rectal/intranasal, benzodiazepine for status epilepticus, where minutes matter.
• Assuming a normal EEG rules out epilepsy.
• Attributing breakthrough seizures to "drug failure" before actively excluding nonadherence and reversible precipitants.
• Stopping an ASM abruptly rather than tapering, including when a patient decides on their own to discontinue.
• Missing folic acid supplementation in a patient of childbearing potential taking an ASM.
• Switching ASM therapy during pregnancy to try to reduce teratogenic risk — this typically increases risk rather than reducing it.
• Failing to address driving and safety counselling after any seizure, regardless of whether the patient raises it.
• Prescribing carbamazepine, gabapentin, oxcarbazepine, phenytoin, or vigabatrin without confirming the seizure type is not absence, myoclonic, or atonic — each can worsen these seizure types.

How to use this table: Doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. This chapter focuses on adult epilepsy management — pediatric dosing for these agents is weight-based and specialist-directed, and is not covered here. Select any drug name to open its complete Pharmasist Drug Database page.

Status Epilepticus (Acute/Parenteral) Agents

Barbiturates

Benzodiazepines (chronic adjunctive therapy)

Carboxylic Acid Derivatives

GABA Derivatives

Hydantoin Derivatives

Iminostilbene Derivatives

Succinimide Derivatives

Other Antiseizure Medications