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Antiseizure Medications

By

Bola Adamolekun

, MD, University of Tennessee Health Science Center

Reviewed/Revised Jan 2024
View PATIENT EDUCATION
Topic Resources

No single medication controls all types of seizures, and different patients require different medications. Some patients require multiple medications. (See also the practice guideline for the treatment of refractory epilepsy from the American Academy of Neurology and the American Epilepsy Society [ 1 General references No single medication controls all types of seizures, and different patients require different medications. Some patients require multiple medications. (See also the practice guideline for the... read more , 2 General references No single medication controls all types of seizures, and different patients require different medications. Some patients require multiple medications. (See also the practice guideline for the... read more ].)

Rarely, an antiseizure medication that is effective for one seizure type may aggravate another seizure type.

General references

  • 1. Kanner AM, Ashman E, Gloss D, et al: Practice guideline update: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 91 (2):74–81, 2018. doi: 10.1212/WNL.0000000000005755 Epub 2018 Jun 13.

  • 2. Kanner AM, Ashman E, Gloss D, et al: Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy. Epilepsy Curr 18 (4):269–278, 2018. doi: 10.5698/1535-7597.18.4.269

Principles of Long-Term Treatment

There are some general principles for using antiseizure medications (also called antiepileptic medications or anticonvulsants):

  • A single medication, usually the first or second one tried, controls epileptic seizures in about 60% of patients.

  • If seizures are difficult to control from the outset (in 30 to 40% of patients), 2 medications may eventually be required.

  • If seizures are intractable (refractory to an adequate trial of 2 medications), patients should be referred to an epilepsy center to determine whether they are candidates for surgery.

Some medications (eg, phenytoin, valproate), given IV or orally, reach the targeted therapeutic range very rapidly. Others (eg, lamotrigine, topiramate) must be started at a relatively low dose and gradually increased over several weeks to the standard therapeutic dose, based on the patient’s lean body mass. Dose should be tailored to the patient’s tolerance of the medication. Some patients have symptoms of medication toxicity when blood levels of a medication are low; others tolerate high levels without symptoms. If seizures continue, the daily dose is increased by small increments.

The appropriate dose of any medication is the lowest dose that stops all seizures and has the fewest adverse effects, regardless of blood level of a medication. Blood levels of medications are only guidelines. Once medication response is known, following the clinical course is more useful than measuring blood levels.

Pearls & Pitfalls

  • Determine the medication dose using clinical criteria (the lowest dose that stops seizures and has the fewest adverse effects), regardless of blood levels.

If toxicity develops before seizures are controlled, the dose is reduced to the pretoxicity dose. Then, another medication is added at a low dose, which is gradually increased until seizures are controlled. Patients should be closely monitored because the 2 medications can interact, interfering with either medication’s rate of metabolic degradation. The initial medication is then slowly tapered and eventually withdrawn completely.

Use of multiple medications should be avoided if possible because incidence of adverse effects, poor adherence, and medication interactions increases significantly. Adding a second medication helps about 10% of patients, but incidence of adverse effects more than doubles. The blood level of antiseizure medications is altered by many other medications, and vice versa. Physicians should be aware of all potential drug-drug interactions before prescribing a new medication.

Once seizures are controlled, the medication should be continued without interruption until patients have been seizure-free for at least 2 years. At that time, stopping the medication may be considered. Most of these medications can be tapered by 10% every 2 weeks.

Relapse is more likely in patients who have had any of the following:

  • A seizure disorder since childhood

  • Need for > 1 medication to be seizure-free

  • Previous seizures while taking an antiseizure medication

  • Focal-onset or myoclonic seizures

  • Underlying static (nonprogressive) encephalopathy

  • Abnormal electroencephalogram (EEG) results within the last year

  • Structural lesions (seen on imaging studies)

Patients who have a relapse when they are not taking antiseizure medications should be treated indefinitely.

Choice of Medication for Long-Term Treatment

The preferred medications vary according to type of seizure (see table ). Other factors that influence choice of medication include adverse effects, interactions with other medications, comorbidities, childbearing plans, and patient preferences.

Traditionally, antiseizure medications have been separated into older and newer groups based on when they became available. However, some so-called newer medications have been available for many years now.

Broad-spectrum antiseizure medications (which are effective for focal-onset seizures and various types of generalized-onset seizures) include

  • Lamotrigine

  • Levetiracetam

  • Topiramate

  • Valproate

  • Zonisamide

For focal-onset seizures and generalized-onset tonic-clonic seizures, the newer antiseizure medications (eg, clobazam, clonazepam, felbamate, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, zonisamide) are no more effective than the established medications. However, the newer medications tend to have fewer adverse effects and to be better-tolerated.

Epileptic (formerly, infantile) spasms, atonic seizures, and myoclonic seizures are difficult to treat. Valproate or vigabatrin is preferred, followed by clonazepam. For epileptic spasms, corticosteroids for 8 to 10 weeks are often effective. The optimal regimen is controversial. Adrenocorticotropic hormone (ACTH) 20 to 60 units IM once a day may be used. A ketogenic diet (a very high fat diet that induces ketosis) may help but is difficult to maintain.

For juvenile myoclonic epilepsy, life-long treatment with valproate or another antiseizure medication is usually recommended. Carbamazepine, oxcarbazepine, or gabapentin can exacerbate the seizures. Lamotrigine can be used as second-line monotherapy (eg, for women of childbearing age) or adjunctive therapy for juvenile myoclonic epilepsy; however, it can aggravate myoclonic seizures in some patients with juvenile myoclonic epilepsy.

For febrile seizures, medications are not recommended unless children have a subsequent seizure in the absence of febrile illness. Previously, many physicians gave phenobarbital or other antiseizure medications to children with complicated febrile seizures to prevent nonfebrile seizures from developing, but this treatment does not appear effective, and long-term use of phenobarbital reduces learning capacity.

For seizures due to alcohol withdrawal, antiseizure medications are not recommended. Instead, treating the withdrawal syndrome tends to prevent seizures. Treatment usually includes a benzodiazepine.

Table

Adverse effects

The different adverse effects of antiseizure medications may influence the choice of medication for an individual patient. For example, antiseizure medications that cause weight gain (eg, valproate) may not be the best option for an overweight patient, and topiramate or zonisamide may not be suitable for patients with history of kidney stones.

Some adverse effects of antiseizure medications can be minimized by increasing the dose gradually.

Overall, the newer antiseizure medications have advantages, such as better tolerability, less sedation, and fewer medication interactions.

All antiseizure medications may cause an allergic scarlatiniform or morbilliform rash.

Some types of seizures may be worsened by certain antiseizure medications. For example, pregabalin and lamotrigine may worsen myoclonic seizures; carbamazepine may worsen absence, myoclonic, and atonic seizures.

Some antiseizure medications (phenobarbital, carbamazepine, phenytoin) are potent inducers of the cytochrome P450 (CYP450) system and may lead to reduced blood levels of several medications, including oral contraceptives, anticoagulants, antiretrovirals, cytotoxic therapy and some other antiseizure medications. They may also lead to lower vitamin D levels, increasing the risk of osteoporosis.

Other adverse effects vary by medication (see Specific Antiseizure Medications ).

Antiseizure medication use during pregnancy

Antiseizure medications are associated with an increased risk of teratogenicity.

Fetal antiepileptic drug syndrome (cleft lip, cleft palate, cardiac defects, microcephaly, growth retardation, developmental delay, abnormal facies, limb or digit hypoplasia) occurs in 4% of children of women who take antiseizure medications during pregnancy.

Yet, because uncontrolled generalized-onset seizures during pregnancy Seizure Disorders in Pregnancy Seizure disorders may impair fertility. But certain antiseizure drugs may make oral contraceptives less effective, resulting in unintentional pregnancy. The dose of antiseizure drugs may have... read more can lead to fetal injury and death, continued treatment with medications is generally advisable. Women should be informed of the risks of antiseizure medications to the fetus, and the risk should be put in perspective: Alcohol is more toxic to the developing fetus than any antiseizure medication.

Many antiseizure medications decrease folate and B12 serum levels; oral vitamin supplements can prevent this effect. Taking folate supplements before conception helps reduce risk of neural tube defects Overview of Congenital Neurologic Anomalies Congenital brain anomalies cause a spectrum of neurologic deficits; although some may be barely noticeable, others may be fatal. Some of the most serious neurologic anomalies (eg, anencephaly... read more and should be recommended to all women who are of childbearing age and who take antiseizure medications.

Risk of teratogenicity is lower with monotherapy and varies by medication; none is completely safe during pregnancy. Risk with carbamazepine, phenytoin, and valproate is relatively high; there is evidence that they have caused congenital malformations in humans (see table ). Risk of neural tube defects is somewhat greater with valproate than other commonly used antiseizure medications. Risk with some of the newer medications (eg, lamotrigine) seems to be less.

Table

Specific Antiseizure Medications

Medication Name

Indications

Adverse Effects

Acetazolamide

Refractory absence seizures

Renal calculi, dehydration, metabolic acidosis

Cannabidiol

Adjunctive therapy for seizures in Lennox-Gastaut syndrome and Dravet syndrome in patients ≥ 2 years

Somnolence, hepatocellular injury with elevated aminotransferases, anorexia, fatigue, insomnia, diarrhea

Carbamazepine

Focal-onset, generalized-onset tonic-clonic, and mixed seizures (but not absence, myoclonic, or atonic seizures)

Diplopia, dizziness, nystagmus, gastrointestinal (GI) upset, dysarthria, lethargy, low white blood cell (WBC) count (3000 to 4000/mcL), hyponatremia, severe rash, including Stevens-Johnson syndrome (in 5%)

Idiosyncratic adverse effects: granulocytopenia, thrombocytopenia, liver toxicity, aplastic anemia

Cenobamate

Adjunctive therapy for focal-onset seizures with or without focal-to-bilateral tonic-clonic generalization

Contraindicated in patients with familial short QT syndrome

Dizziness, diplopia, somnolence, fatigue

Rarely, medication reaction with eosinophilia and systemic symptoms (DRESS), shortening of QT interval, suicidal ideation

Clobazam

Absence seizures

Adjunctive therapy for tonic or atonic seizures in Lennox-Gastaut syndrome and for refractory focal-onset seizures with or without focal-to-bilateral tonic-clonic generalization

Somnolence, sedation, constipation, ataxia, suicidal thoughts, medication dependency, irritability, dysphagia

Clonazepam

Atypical absence seizures in Lennox-Gastaut syndrome, atonic and myoclonic seizures, epileptic spasms

Possibly absence seizures refractory to ethosuximide

Drowsiness, ataxia, behavioral abnormalities, partial or complete tolerance to beneficial effects, usually in 1 to 6 months*

Divalproex

Same indications as valproate: Absence seizures (typical and atypical), focal-onset seizures, tonic-clonic seizures, myoclonic seizures, juvenile myoclonic epilepsy, epileptic spasms, neonatal or febrile seizures, tonic or atonic seizures in Lennox-Gastaut syndrome

Nausea, vomiting, GI intolerance, weight gain, reversible alopecia, transient drowsiness, transient neutropenia, tremor

Idiosyncratically, hyperammonemic encephalopathy

Rarely, fatal hepatic necrosis, particularly in young neurologically impaired children treated with multiple antiseizure medications

Eslicarbazepine

Focal-onset seizures as monotherapy or adjunctive therapy

Not recommended for use in patients with severe hepatic impairment

Dizziness, diplopia, somnolence, hyponatremia, suicidal ideation, dermatologic reactions (including Stevens-Johnson syndrome); significant medication reactions possible

Ethosuximide

Absence seizures

Nausea, lethargy, dizziness, headache

Idiosyncratically, leukocytopenia or pancytopenia, dermatitis, systemic lupus erythematosus

Felbamate

Refractory focal-onset seizures, atypical absence seizures in Lennox-Gastaut syndrome

Headache, fatigue, liver failure; rarely, aplastic anemia

Fosphenytoin

Status epilepticus

Ataxia, dizziness, somnolence, headache, pruritus, paresthesias

Gabapentin

Adjunctive therapy for focal-onset seizures in patients aged 3 to 12 years and as adjunctive therapy for focal-onset seizures with or without focal-to-bilateral tonic-clonic seizures in patients aged ≥ 12 years

Drowsiness, dizziness, weight gain, headache

In patients aged 3 to 12 years, somnolence, aggressive behavior, mood lability, hyperactivity

Lacosamide

Second-line monotherapy or adjunctive therapy for focal-onset seizures in patients ≥ 17 years

Adjunctive therapy for primary generalized tonic-clonic seizures in patients ≥ 4 years

Dizziness, diplopia, suicidal thoughts

Lamotrigine

Adjunctive therapy for focal-onset seizures in patients ≥ 2 years, generalized-onset seizures in Lennox-Gastaut syndrome, generalized-onset tonic-clonic seizures

In patients ≥ 16 years, substitution monotherapy for focal-onset or focal-to-bilateral tonic-clonic seizures after a concomitantly used enzyme-inducing antiseizure medication (eg, carbamazepine, phenytoin, phenobarbital) or valproate is stopped

Headache, dizziness, drowsiness, insomnia, fatigue, nausea, vomiting, diplopia, ataxia, tremor, menstrual abnormalities, rash (in 2 to 3%), which progresses to Stevens-Johnson syndrome in 1/50 to 100 children and 1/1000 adults

Exacerbation of myoclonic seizures in adults

Levetiracetam

Status epilepticus

Adjunctive therapy for focal-onset seizures in patients ≥ 4 years, generalized-onset tonic-clonic seizures in patients > 6 years, myoclonic seizures in patients > 12 years, and juvenile myoclonic epilepsy

Fatigue, weakness, ataxia, mood and behavioral changes

Oxcarbazepine

Focal-onset seizures in patients aged 4 to 16 years as adjunctive therapy and for focal-onset seizures in adults

Fatigue, nausea, abdominal pain, headache, dizziness, somnolence, leukopenia, diplopia, hyponatremia (in 2.5%).

Perampanel

Adjunctive therapy for focal-onset seizures and generalized-onset tonic-clonic seizures in people who have epilepsy and are ≥ 12 years

Not indicated for use in children < 4 years

Aggressiveness, mood and behavioral changes, suicidal ideation, dizziness, somnolence, fatigue, irritability, falls, headache, nausea, vomiting, abdominal pain, weight gain, gait disturbances

Phenobarbital

Generalized-onset tonic-clonic seizures, focal-onset seizures, status epilepticus, neonatal seizures

Drowsiness, nystagmus, ataxia,

In children, learning difficulties, paradoxical hyperactivity

Idiosyncratically, anemia, rash

Phenytoin

Focal-to-bilateral tonic-clonic seizures, focal impaired-awareness seizures, convulsive status epilepticus

Prevention of seizures secondary to head trauma

Megaloblastic anemia, gingival hyperplasia, hirsutism, adenopathy, loss of bone density

With high blood levels of, phenytoin, nystagmus, ataxia, dysarthria, lethargy, irritability, nausea, vomiting, confusion

Idiosyncratically, rash, exfoliative dermatitis

Rarely, exacerbation of seizures

Pregabalin

Adjunctive therapy for focal-onset seizures

Dizziness, somnolence, ataxia, blurred vision, diplopia, tremor, weight gain

Exacerbation of myoclonic seizures

Tiagabine

Adjunctive therapy for focal-onset seizures in patients ≥ 12 years

Dizziness, light-headedness, confusion, slowed thinking, fatigue, tremor, sedation, nausea, abdominal pain

Topiramate

Focal-onset seizures in patients ≥ 2 years, atypical absence seizures

Second-line monotherapy or adjunctive therapy for primarily generalized tonic-clonic seizures

Decreased concentration, paresthesias, fatigue, speech dysfunction, confusion, anorexia, weight loss, reduced sweating, metabolic acidosis, nephrolithiasis (in 1 to 5%), psychosis (in 1%)

Valproate

Absence seizures (typical and atypical), focal-onset seizures, tonic-clonic seizures, myoclonic seizures, juvenile myoclonic epilepsy, epileptic spasms, neonatal or febrile seizures, tonic or atonic seizures in Lennox-Gastaut syndrome

Status epilepticus

Not generally recommended for women of childbearing age

Nausea, vomiting, GI intolerance, weight gain, reversible alopecia (in 5%), transient drowsiness, transient neutropenia, tremor

Idiosyncratically, hyperammonemic encephalopathy

Rarely, fatal hepatic necrosis, particularly in young neurologically impaired children treated with multiple antiseizure medications

Vigabatrin

Adjunctive therapy for focal-onset seizures

Epileptic spasms

Drowsiness, dizziness, headache, fatigue, irreversible visual field defects (requires regular visual field evaluations)

Zonisamide

Adjunctive therapy for focal-onset seizures in patients ≥ 16 years, alternative or adjunctive therapy for tonic or atonic seizures in Lennox-Gastaut syndrome

Depression, psychosis, urinary calculi, oligohidrosis

* Serious reactions to clonazepam are rare.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

  • Kanner AM, Ashman E, Gloss D, et al: Practice guideline update: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

  • Kanner AM, Ashman E, Gloss D, et al: Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy.

Drugs Mentioned In This Article

Drug Name Select Trade
Dilantin, Dilantin Infatabs, Dilantin-125, Phenytek
Lamictal, Lamictal CD, Lamictal ODT, Lamictal XR, Subvenite
EPRONTIA, Qudexy XR, Topamax, Topamax Sprinkle, Topiragen , Trokendi XR
ELEPSIA XR, Keppra, Keppra XR, Roweepra , Spritam
Zonegran, ZONISADE
ONFI, Sympazan
Ceberclon , Klonopin
Felbatol
Motpoly XR, Vimpat
Oxtellar XR, Trileptal
Lyrica, Lyrica CR
Gabitril
Sabril, VIGADRONE, VIGPODER
Carbatrol, Epitol , Equetro, Tegretol, Tegretol -XR
Active-PAC with Gabapentin, Gabarone , Gralise, Horizant, Neurontin
Luminal, Sezaby
Calcidol, Calciferol, D3 Vitamin, DECARA, Deltalin, Dialyvite Vitamin D, Dialyvite Vitamin D3, Drisdol, D-Vita, Enfamil D-Vi-Sol, Ergo D, Fiber with Vitamin D3 Gummies Gluten-Free, Happy Sunshine Vitamin D3, MAXIMUM D3, PureMark Naturals Vitamin D, Replesta, Replesta Children's, Super Happy SUNSHINE Vitamin D3, Thera-D 2000, Thera-D 4000, Thera-D Rapid Repletion, THERA-D SPORT, UpSpring Baby Vitamin D, UpSpring Baby Vitamin D3, YumVs, YumVs Kids ZERO, YumVs ZERO
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