Generalized seizures in children

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute repetitive seizures (children >1 month of age)

in the community

1st line – benzodiazepine

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1st line –

benzodiazepine

There is no well-established definition of acute repetitive seizures, which adds to the challenge of recognizing them.[44] One frequently used clinical definition is three or more seizures within 24 hours for patients whose habitual seizure frequency is fewer than three seizures per day, with return to full alertness between seizures. Other definitions include two or more seizures in 6 hours, two or more seizures in 24 hours, or two to four seizures in less than 48 hours.[44]

A child having a convulsive seizure should be immediately placed on their side to prevent injury, and the airway cleared. The child's parents and other caregivers should be trained to administer treatments as soon as possible in the community when seizure clusters are identified, without the need for the patient to attend the hospital.

Treatment options include rectal or intranasal diazepam, or buccal or intranasal midazolam. These benzodiazepine formulations have shown reasonable efficacy, equal to or better than that of intravenous formulations, in most patients. Oral benzodiazepines (e.g., lorazepam) can be used if the above formulations are not available, provided that the patient is awake and cooperative, and the risk of aspiration is low or not a concern.[42][43]

The patient should be continued on a suitable oral formulation of an anticonvulsant once stabilized.

Primary options

diazepam rectal: children 2-5 years of age: 0.5 mg/kg rectally as a single dose; children 6-11 years of age: 0.3 mg/kg rectally as a single dose; children ≥12 years of age: 0.2 mg/kg rectally as a single dose

diazepam nasal: children 6-11 years of age and body weight 10-18 kg: 5 mg intranasally as a single dose; children 6-11 years of age and body weight 19-37 kg: 10 mg intranasally as a single dose; children 6-11 years of age and body weight 38-55 kg: 15 mg intranasally as a single dose; children 6-11 years of age and body weight 56-74 kg: 20 mg intranasally as a single dose; children ≥12 years of age and body weight 14-27 kg: 5 mg intranasally as a single dose; children ≥12 years of age and body weight 28-50 kg: 10 mg intranasally as a single dose; children ≥12 years of age and body weight 51-75 kg: 15 mg intranasally as a single dose; children ≥12 years of age and body weight ≥76 kg: 20 mg intranasally as a single dose

midazolam nasal: children ≥12 years of age: 5 mg (1 spray) intranasally as a single dose

midazolam: children ≥1 month of age: 0.2 mg/kg buccally as a single dose, maximum 10 mg/dose

Secondary options

lorazepam: consult specialist for guidance on dose

in the hospital

1st line – parenteral benzodiazepine or anticonvulsant

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1st line –

parenteral benzodiazepine or anticonvulsant

The child should be immediately placed on their side to prevent injury, and the airway cleared.

In a hospital setting, intravenous benzodiazepines (e.g., diazepam, lorazepam), or intravenous formulations of anticonvulsants such as phenytoin (or fosphenytoin), valproic acid, phenobarbital, levetiracetam, lacosamide, and brivaracetam can be used to treat acute repetitive seizures. The patient should be continued on a suitable oral formulation of an anticonvulsant once stabilized.

Valproic acid is contraindicated in patients with urea cycle disorders and some mitochondrial disorders, especially those caused by mitochondrial DNA polymerase gamma, and should be avoided in children under age 2 years unless these causes are excluded.[81][83] Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

For patients with the potential to become pregnant, see "Considerations for patients of childbearing potential" in Management approach.

Primary options

diazepam: children ≥1 month of age: 0.15 to 0.2 mg/kg intravenously as a single dose, may repeat dose within 15 minutes, maximum 10 mg/dose

lorazepam: 0.05 to 0.1 mg/kg intravenously as a single dose, may repeat 0.05 mg/kg after 10-15 minutes according to response, maximum 4 mg/dose

Secondary options

phenytoin: 15-20 mg/kg intravenously as a loading dose, followed by an additional dose of 5-10 mg/kg after 10-20 minutes according to response, maximum 1500 mg/day

fosphenytoin: 15-20 mg (phenytoin equivalents)/kg intravenously as a loading dose, followed by an additional dose of 5-10 mg (phenytoin equivalents)/kg after 10-20 minutes according to response, maximum 1500 mg (phenytoin equivalents)/day

phenobarbital: 15-20 mg/kg intravenously as a single dose, followed by 5-10 mg/kg every 15-30 minutes according to response, maximum 1000 mg/loading dose and 40 mg/kg/total dose

valproic acid: 40 mg/kg intravenously as a single dose, maximum 3000 mg/dose

levetiracetam: 60 mg/kg intravenously as a single dose, maximum 4500 mg/dose

lacosamide: consult specialist for guidance on dose

brivaracetam: consult specialist for guidance on dose

ONGOING

epilepsy syndromes with onset in infancy (1 month to 2 years)

early infantile developmental and epileptic encephalopathy (EIDEE)

1st line – pyridoxine and/or anticonvulsants

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1st line –

pyridoxine and/or anticonvulsants

Careful efforts to identify genetic, metabolic, and/or structural etiology are necessary to guide etiology-specific treatments.

Pyridoxine-dependent epilepsy is an important and potentially treatable cause of early-onset therapy-resistant epilepsy. Prompt recognition is important for treatment and prognosis. Infants with early-onset therapy-resistant epilepsy of unknown cause should receive pyridoxine with or without additional anticonvulsants until pyridoxine-dependent epilepsy is fully excluded by metabolic and/or genetic analysis.[68]

Conventional anticonvulsants are options for treatment of EIDEE, but their efficacy is limited. Zonisamide, vigabatrin, topiramate, and high doses of phenobarbital may be of some value.[69][70][71]

Vigabatrin may cause permanent vision loss and has restricted distribution in some countries.

Sodium-channel-blocking drugs, such as oxcarbazepine, should be considered optimal therapy when the epileptic encephalopathy is suspected to be due to gain-of-function pathogenic variants of SCN2A/SCN8A or loss-of-function KCNQ2 variants.

Quinidine has been used to treat epilepsy associated with gain-of-function KCNT1 variants, but studies have yielded contradictory results.[72][73]

Patients may need monotherapy or combination therapy. The list of drugs here reflects options that may be used; however, combinations of these drugs may be required in practice. It is important to take into account any drug interactions between anticonvulsants, and any drug interactions between anticonvulsants and any other drug the patient may be taking.

Primary options

pyridoxine (vitamin B6): consult specialist for guidance on dose

zonisamide: consult specialist for guidance on dose

vigabatrin: consult specialist for guidance on dose

topiramate: consult specialist for guidance on dose

phenobarbital: consult specialist for guidance on dose

oxcarbazepine: consult specialist for guidance on dose

Secondary options

quinidine sulfate: consult specialist for guidance on dose

2nd line – ketogenic diet or surgery

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2nd line –

ketogenic diet or surgery

Ketogenic diets should be considered for patients with refractory epilepsy. Use requires a skilled team including a dietitian, and regular monitoring.[62][63] [ ] [ ]

Surgery (resection, disconnection) may be effective if the majority of seizures are focal and due to an identified structural cause. It is important to identify potential structural etiology and consider surgery early if seizures are refractory to drug treatment.[74]

infantile epileptic spasms syndrome (IESS) (including West syndrome)

1st line – corticosteroid or corticotropin (ACTH) or vigabatrin

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1st line –

corticosteroid or corticotropin (ACTH) or vigabatrin

Epileptic spasms are resistant to most anticonvulsants. An oral corticosteroid, ACTH, or vigabatrin (the treatment of choice for patients with tuberous sclerosis complex) should be used as initial treatment as soon as infantile epileptic spasms are diagnosed, as all have shown efficacy in studies.[75][76][77][78]

ACTH and corticosteroids have similar reported efficacy: 46% and 44% of patients, respectively, showed a response to treatment in one study. Response rates to vigabatrin were 62% for infants with tuberous sclerosis complex and 29% for those with other causes of infantile spasms.[79] The presence or absence of hypsarrhythmia should not impact treatment decisions.[80]

Vigabatrin may cause permanent vision loss and has restricted distribution in some countries.

Recommendations regarding drug regimen, doses, and duration of treatment vary. The most common regimen is ACTH, followed by a corticosteroid (usually prednisone). Treatment dose may need to be escalated quickly in an attempt to stop spasms and improve electroencephalogram (EEG). A specialist should be consulted for guidance on choice of regimen.

If the first treatment is ineffective, an alternative medication from the initial options that has a different mechanism of action should be tried, as these are more effective than using standard anticonvulsants: that is, vigabatrin if prednisone or ACTH was used as the primary option, and prednisone or ACTH if vigabatrin was used as the primary option.[81] Alternatively, prednisone or ACTH may be used in combination with vigabatrin; there is some evidence for improved seizure control with combination therapy, but no good evidence that it changes long-term outcomes.[82]

Primary options

prednisone: consult specialist for guidance on dose

corticotropin: consult specialist for guidance on dose

vigabatrin: consult specialist for guidance on dose

Secondary options

prednisone: consult specialist for guidance on dose

corticotropin: consult specialist for guidance on dose

-- AND --

vigabatrin: consult specialist for guidance on dose

2nd line – alternative anticonvulsants or ketogenic diet or surgery

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2nd line –

alternative anticonvulsants or ketogenic diet or surgery

Evidence for the effectiveness of other treatments for refractory IESS is limited. Choice of treatment should be made on an individual patient-specific basis.

There is insufficient evidence for efficacy of other anticonvulsants for the treatment of refractory infantile spasms. Medications used have included topiramate, clobazam, valproic acid, zonisamide, levetiracetam, and phenobarbital. Valproic acid is contraindicated in patients with urea cycle disorders and some mitochondrial disorders, especially those caused by mitochondrial DNA polymerase gamma, and should be avoided in children under age 2 years unless these causes are excluded.[81][83]

Pyridoxine is sometimes used as a treatment option, although one study reported that add-on pyridoxine was ineffective.[84][85][86]

Ketogenic diets are an effective option for intractable epileptic spasms.[63] However, effects may be temporary, so use is reserved for hormone-resistant cases. Use requires a skilled team including a dietitian, and regular monitoring.[62][63]

For children with drug-resistant epileptic spasms who have localized brain abnormalities (especially when they correlate with EEG localization), surgery (resection, disconnection) is considered appropriate. Structural abnormalities (e.g., tumors, porencephaly, hemimegalencephaly) are indications for surgery with good potential outcome. Focal cortical dysplasia is also an indication, especially if it correlates with EEG findings. Early surgery is suggested for drug-resistant cases, because early intervention may lead to better cognitive prognosis.

myoclonic epilepsy in infancy (MEI)

1st line – anticonvulsants

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1st line –

anticonvulsants

Valproic acid monotherapy is generally considered effective in patients with MEI.[87][88] Valproic acid is contraindicated in patients with urea cycle disorders and some mitochondrial disorders, especially those caused by mitochondrial DNA polymerase gamma, and should be avoided in children under age 2 years unless these causes are excluded. Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

Other treatment options include topiramate, lamotrigine, clonazepam, and levetiracetam.[69]

Lamotrigine may cause serious and life-threatening dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

There is a suggestion that delays in the start of treatment may cause cognitive problems later in life.[89]

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

Secondary options

clonazepam: children <10 years of age or body weight <30 kg: 0.01 to 0.03 mg/kg/day orally given in 2-3 divided doses initially, increase gradually according to response, maximum 0.2 mg/kg/day; children ≥10 years of age or body weight ≥30 kg: 0.5 mg orally three times daily initially, increase gradually according to response, maximum 20 mg/day

topiramate: consult specialist for guidance on dose

lamotrigine: consult specialist for guidance on dose

levetiracetam: consult specialist for guidance on dose

Dravet syndrome

1st line – anticonvulsants

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1st line –

anticonvulsants

Valproic acid and clobazam are recommended as initial therapies.[21][90][91]

Valproic acid is contraindicated in patients with urea cycle disorders and some mitochondrial disorders, especially those caused by mitochondrial DNA polymerase gamma, and should be avoided in children under age 2 years unless these causes are excluded. Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

If valproic acid and clobazam are insufficiently effective, stiripentol and/or fenfluramine should be considered.[21][90][91]

Stiripentol (a cytochrome P450 inhibitor that increases blood levels of other anticonvulsants) is effective when added to clobazam, and when used as monotherapy (off-label). It is approved for use as adjunctive therapy with clobazam for Dravet syndrome in children from age 6 months.[21][91][92] Stiripentol may cause neutropenia and thrombocytopenia; hematologic testing should be performed before and during treatment.

Fenfluramine (a serotonin receptor agonist) is approved to treat seizures related to Dravet syndrome in patients ages 2 years and older. It may be used as monotherapy or in combination with other drugs. In randomized controlled trials, fenfluramine resulted in significantly greater reduction in the frequency of convulsive seizures compared with placebo.[21][93] Fenfluramine is associated with valvular heart disease and pulmonary arterial hypertension; an ECG should be performed before and during treatment.

Cannabidiol oral solution is approved for the treatment of seizures associated with Dravet syndrome for patients ages 1 year and older (2 years and older in some countries). Pharmaceutical-grade cannabidiol is associated with a decrease in the frequency of seizures related to Dravet syndrome, although the mechanism of action is unknown.[94][95] There is evidence that cannabidiol is effective in the absence as well as in the presence of clobazam.[96][97] Use cannabidiol with caution in patients with hepatic disease.

Sodium-channel-blocking drugs such as carbamazepine, oxcarbazepine, lamotrigine, and phenytoin are known to exacerbate seizures in children with Dravet syndrome, and should be avoided.[21][91]

For patients with the potential to become pregnant, see "Considerations for patients of childbearing potential" in Management approach.

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

clobazam: children ≥2 years of age and body weight ≤30 kg: 5 mg orally once daily initially, increase gradually according to response, maximum 20 mg/day given in 2 divided doses; children ≥2 years of age and body weight >30 kg: 5 mg orally twice daily initially, increase gradually according to response, maximum 40 mg/day given in 2 divided doses

Secondary options

stiripentol: children ≥6 months of age and ≥7 kg body weight: 50 mg/kg/day orally given in 2 divided doses initially, increase gradually according to response, maximum 3000 mg/day

and

fenfluramine: children ≥2 years of age: 0.1 mg/kg orally twice daily initially, increase gradually according to response, maximum 0.7 mg/kg/day or 26 mg/day

Tertiary options

cannabidiol (CBD): children ≥1 year of age: 2.5 mg/kg orally twice daily initially, increase gradually according to response, maximum 20 mg/kg/day

2nd line – topiramate

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2nd line –

topiramate

Topiramate may be used as monotherapy or adjunctively. Efficacy of topiramate when used as adjunctive therapy has been reported.[21][98]

Primary options

topiramate: consult specialist for guidance on dose

2nd line – ketogenic diet

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2nd line –

ketogenic diet

Ketogenic diets are effective, and should be considered after two unsuccessful anticonvulsant trials, or earlier in some cases. Use requires a skilled team including a dietitian, and regular monitoring.[62][63]

3rd line – vagus nerve stimulation

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3rd line –

vagus nerve stimulation

Vagus nerve stimulation typically results in a <50% reduction in seizures, but should be considered only after other therapeutic options have been tried.[21]

genetic epilepsy with febrile seizures plus (GEFS+)

1st line – anticonvulsants

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1st line –

anticonvulsants

Seizures typically respond to treatment with anticonvulsants.[32] Treatment options include valproic acid, lamotrigine, levetiracetam, or topiramate.

Valproic acid is contraindicated in patients with urea cycle disorders and some mitochondrial disorders, especially those caused by mitochondrial DNA polymerase gamma, and should be avoided in children under age 2 years unless these causes are excluded. Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

Lamotrigine may cause serious and life-threatening dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

For patients with the potential to become pregnant, see "Considerations for patients of childbearing potential" in Management approach.

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

lamotrigine: consult specialist for guidance on dose

levetiracetam: consult specialist for guidance on dose

topiramate: consult specialist for guidance on dose

epilepsy syndromes with onset in childhood (2-12 years)

epilepsy with myoclonic-atonic seizures (EMAtS; Doose syndrome)

1st line – anticonvulsant and/or ketogenic diet

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1st line –

anticonvulsant and/or ketogenic diet

Valproic acid is recommended most often as first-line therapy.[100][101] Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

Ketogenic diets are highly effective for this syndrome.[101] In one study of a large retrospective multicenter cohort, therapy with a ketogenic diet was by far the most effective treatment, and it therefore should be considered as initial therapy.[99] Use requires a skilled team including a dietitian, and regular monitoring.[62][63]

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

2nd line – alternative anticonvulsants

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2nd line –

alternative anticonvulsants

Treatments with evidence of effectiveness are benzodiazepines (e.g., clobazam, clonazepam), levetiracetam, zonisamide, and topiramate.[101]

Lamotrigine, ethosuximide, rufinamide, perampanel, and felbamate also have some evidence of effectiveness.[101]

Lamotrigine may cause serious and life-threatening dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

Perampanel may cause severe psychiatric and behavioral reactions (e.g., aggression, hostility, homicidal ideation); monitor patients closely during dose titration and at higher doses.

Felbamate may cause aplastic anemia or hepatic failure; hematologic testing and liver function testing should be performed before and during treatment.

Vigabatrin and sodium-channel-blocking drugs other than lamotrigine should be avoided.[101]

Primary options

levetiracetam: children ≥6 years of age: 20 mg/kg/day orally (immediate-release)/intravenously initially given in 2 divided doses, increase gradually according to response, maximum 60 mg/kg/day or 3000 mg/day; children ≥16 years of age: 500 mg orally (immediate-release)/intravenously twice daily initially, increase gradually according to response, maximum 3000 mg/day

zonisamide: children 1-15 years of age: consult specialist for guidance on dose; children ≥16 years of age: 100 mg orally once daily initially, increase gradually according to response, maximum 600 mg/day

topiramate: children ≥2 years of age: 1-3 mg/kg orally (immediate-release) once daily initially, increase gradually according to response, maximum 9 mg/kg/day or 400 mg/day

Secondary options

lamotrigine: consult specialist for guidance on dose

ethosuximide: children 3-6 years of age: 250 mg orally once daily initially, increase gradually according to response, maximum 20 mg/kg/day or 1500 mg/day given in 2 divided doses; children ≥6 years of age: 250 mg orally twice daily initially, increase gradually according to response, maximum 20 mg/kg/day or 1500 mg/day given in 2 divided doses

rufinamide: children ≥1 year of age: 10 mg/kg/day orally given in 2 divided doses initially, increase gradually according to response, maximum 45 mg/kg/day or 3200 mg/day

perampanel: children ≥12 years of age: 2-4 mg orally once daily at bedtime initially, increase gradually according to response, maximum 12 mg/day

felbamate: children 2-14 years of age: 15 mg/kg/day orally given in 3-4 divided doses initially, increase dose gradually according to response, maximum 45 mg/kg/day or 3600 mg/day

3rd line – vagus nerve stimulation or corpus callosotomy

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3rd line –

vagus nerve stimulation or corpus callosotomy

Vagus nerve stimulation or corpus callosotomy (for drop attacks) may be considered only if medications and ketogenic diets are insufficiently effective.[101]

Lennox-Gastaut syndrome (LGS)

1st line – anticonvulsants

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1st line –

anticonvulsants

LGS is significantly resistant to therapy, and monotherapy with an anticonvulsant is rarely effective. This often means that polytherapy at high doses is required, which may lead to a paradoxical increase in seizure frequency. Careful discussion with caregivers about treatment goals is necessary to balance seizure control with medication adverse effects. Goals are typically to decrease the burden of seizures that are prolonged or associated with injury, but seizure freedom is unlikely.

Valproic acid is the most commonly used first-line agent. Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

Clobazam may also be considered first line as monotherapy, or in combination with valproic acid.

Other anticonvulsants with evidence of effectiveness for treating seizures associated with LGS include rufinamide, lamotrigine, topiramate, cannabidiol, and fenfluramine.[102][103][104][105][106] [ ]

Lamotrigine may cause serious and life-threatening dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

Cannabidiol oral solution is approved for the treatment of seizures associated with LGS in patients ages 1 year and older (2 years and older in some countries). In randomized, double-blind, placebo-controlled trials, adjunctive cannabidiol oral solution effectively reduced the frequency of drop seizures compared with placebo.[104][107][108] There is some evidence that cannabidiol is effective in the absence as well as in the presence of clobazam.[96][97] Adverse effects of cannabidiol include elevated liver enzymes, gastrointestinal intolerance, and sleep disturbances.[95][109] Use cannabidiol with caution in patients with hepatic disease.

Fenfluramine is approved for the treatment of seizures associated with LGS in patients ages 2 years and older. One randomized controlled trial and an open-label extension study showed that fenfluramine resulted in a significantly greater reduction in drop seizures than placebo in patients with LGS; this effect appeared to be greatest in patients with generalized tonic-clonic seizures.[110][111] Fenfluramine is associated with valvular heart disease and pulmonary arterial hypertension; an ECG should be performed before and during treatment.

Other anticonvulsants that may be considered include levetiracetam, perampanel, zonisamide, felbamate, lacosamide, brivaracetam, and cenobamate (not licensed for use in children), although in some cases evidence of effectiveness in LGS is scarce or uncertain.[102][104][105][112]

Perampanel may cause severe psychiatric and behavioral reactions (e.g., aggression, hostility, homicidal ideation); monitor patients closely during dose titration and at higher doses.

Felbamate may cause aplastic anemia or hepatic failure; hematologic testing and liver function testing should be performed before and during treatment.

Carbamazepine, eslicarbazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, and vigabatrin may exacerbate seizures associated with LGS, and so are usually avoided.[105]

For patients with the potential to become pregnant, see "Considerations for patients of childbearing potential" in Management approach.

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

and/or

Secondary options

lamotrigine: consult specialist for guidance on dose

topiramate: children ≥2 years of age: 1-3 mg/kg orally (immediate-release) once daily initially, increase gradually according to response, maximum 9 mg/kg/day or 400 mg/day

cannabidiol (CBD): children ≥1 year of age: 2.5 mg/kg orally twice daily initially, increase gradually according to response, maximum 20 mg/kg/day

fenfluramine: children ≥2 years of age: 0.1 mg/kg orally twice daily initially, increase gradually according to response, maximum 0.7 mg/kg/day or 26 mg/day

rufinamide: children ≥1 year of age: 10 mg/kg/day orally given in 2 divided doses initially, increase gradually according to response, maximum 45 mg/kg/day or 3200 mg/day

Tertiary options

perampanel: children ≥12 years of age: 2-4 mg orally once daily at bedtime initially, increase gradually according to response, maximum 12 mg/day

felbamate: children 2-14 years of age: 15 mg/kg/day orally given in 3-4 divided doses initially, increase dose gradually according to response, maximum 45 mg/kg/day or 3600 mg/day

lacosamide: children ≥4 years of age and body weight 11-30 kg: 1 mg/kg orally/intravenously twice daily initially, increase gradually according to response, maximum 12 mg/kg/day; children ≥4 years of age and body weight 30-50 kg: 1 mg/kg orally/intravenously twice daily initially, increase gradually according to response, maximum 8 mg/kg/day; children ≥4 years of age and body weight ≥50 kg: 50 mg orally/intravenously twice daily initially, increase gradually according to response, maximum 400 mg/day

brivaracetam: children ≥1 month of age and body weight <11 kg: 0.75 to 1.5 mg/kg orally twice daily initially, increase gradually according to response, maximum 6 mg/kg/day; children ≥1 month of age and body weight 11-20 kg: 0.5 to 1.25 mg/kg orally twice daily initially, increase gradually according to response, maximum 5 mg/kg/day; children ≥1 month of age and body weight 20-50 kg: 0.5 to 1 mg/kg orally twice daily initially, increase gradually according to response, maximum 4 mg/kg/day; children ≥1 month of age and body weight >50 kg: 25-50 mg orally twice daily initially, increase gradually according to response, maximum 200 mg/day

cenobamate: consult specialist for guidance on dose

Consider – corticotropin (ACTH) and/or corticosteroid

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Consider –

corticotropin (ACTH) and/or corticosteroid

Treatment recommended for SOME patients in selected patient group

Corticosteroids and/or ACTH may be indicated for short-term adjunctive treatment during a particularly difficult period (i.e., at onset, in status epilepticus, or during a period of significant seizure exacerbation). Recommendations regarding drug regimen, doses, and duration of treatment vary. A specialist should be consulted for guidance on choice of regimen in this age group.

2nd line – nonpharmacologic therapies

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2nd line –

nonpharmacologic therapies

Nonpharmacologic therapies that may be tried include ketogenic diets, vagus nerve stimulation, corpus callosotomy, or (if there is a dominant and/or structural seizure focus) resective surgery.[63][104][113] Use of a ketogenic diet requires a skilled team including a dietitian, and regular monitoring.[62][63]

childhood absence epilepsy (CAE)

1st line – anticonvulsants

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1st line –

anticonvulsants

Generalized-onset tonic-clonic seizures occur in some absence epilepsies. In this case, treatment should be directed at treating both the tonic-clonic seizures and the absences.[7]

In children with absence seizures only, ethosuximide is the first-line option.[114]

Valproic acid is the recommended first-line anticonvulsant for patients with both absences and tonic-clonic seizures, but the adverse-effect profile is not as favorable as that of ethosuximide.[114][115][116] Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

One Cochrane review supports the use of lamotrigine and levetiracetam as suitable alternatives to valproic acid, particularly for patients of childbearing potential for whom valproic acid may not be an appropriate therapy due to teratogenicity.[115] [ ]

Lamotrigine may be added to valproic acid therapy, or other polypharmacy may be required, for refractory cases.[27][117] Lamotrigine may cause serious and life-threatening dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

Topiramate, benzodiazepines (e.g., clobazam, clonazepam), perampanel, and zonisamide are further options.[118][119][120]

Perampanel may cause severe psychiatric and behavioral reactions (e.g., aggression, hostility, homicidal ideation); monitor patients closely during dose titration and at higher doses.

Gabapentin is not effective in these patients, and evidence suggests that carbamazepine and vigabatrin may exacerbate absence seizures.[121] Therefore, use of these agents is not recommended.[27]

For patients with the potential to become pregnant, see "Considerations for patients of childbearing potential" in Management approach.

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

Secondary options

lamotrigine: consult specialist for guidance on dose

Tertiary options

topiramate: children ≥2 years of age: 1-3 mg/kg orally (immediate-release) once daily initially, increase gradually according to response, maximum 9 mg/kg/day or 400 mg/day

perampanel: children ≥12 years of age: 2-4 mg orally once daily at bedtime initially, increase gradually according to response, maximum 12 mg/day

epilepsy with myoclonic absence (EMA)

1st line – anticonvulsants

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1st line –

anticonvulsants

EMA is often refractory to anticonvulsants, and combinations of drugs (polypharmacy) may be required.

Medications commonly used include valproic acid, ethosuximide, lamotrigine, levetiracetam, and benzodiazepines (e.g., clobazam, clonazepam).[115][122] [ ]

Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

Lamotrigine may cause serious and life-threatening dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

For patients with the potential to become pregnant, see "Considerations for patients of childbearing potential" in Management approach.

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

lamotrigine: consult specialist for guidance on dose

epilepsy with eyelid myoclonia (EEM)

1st line – anticonvulsants

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1st line –

anticonvulsants

This syndrome tends to be resistant to drug therapy, with up to 80% of patients developing medically intractable epilepsy and requiring polypharmacy. Generalized tonic-clonic seizures are often responsive to treatment, while eyelid myoclonia are not fully controlled.[33]

Valproic acid, lamotrigine, and levetiracetam are recommended as first-line treatment options, and may reduce seizures by more than 50%.[123][124][125] Levetiracetam and lamotrigine should particularly be considered for patients of childbearing potential due to the teratogenic risks of valproic acid.[123][124]

Lamotrigine may cause serious and life-threatening dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

There is some evidence for effectiveness of ethosuximide and clobazam.[123][124]

For patients with the potential to become pregnant, see "Considerations for patients of childbearing potential" in Management approach.

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

lamotrigine: consult specialist for guidance on dose

Secondary options

Consider – lens therapy

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Consider –

lens therapy

Treatment recommended for SOME patients in selected patient group

Lens therapy may be trialed for patients with a photoparoxysmal response, although evidence for effectiveness is limited.[123][124]

2nd line – alternative anticonvulsants and/or ketogenic diet

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2nd line –

alternative anticonvulsants and/or ketogenic diet

There is no consensus for other treatments for EEM.[123]

Other anticonvulsant medication (e.g., topiramate, brivaracetam, zonisamide, cannabidiol, fenfluramine, clonazepam, perampanel, lacosamide, and acetazolamide) may be tried, but there is little evidence for effectiveness in EEM.[123][124]

Cannabidiol can worsen seizures, especially eyelid myoclonia, and should be used with caution.[124]

Sodium-channel-blocking drugs, except for lamotrigine, may worsen seizures and should be avoided.[123][124]

Data on the use of ketogenic diets in EEM are limited.[123][124] Use of a ketogenic diet requires a skilled team including a dietitian, and regular monitoring.[62][63]

Consider – lens therapy

Back

Consider –

lens therapy

Treatment recommended for SOME patients in selected patient group

Lens therapy may be trialed for patients with a photoparoxysmal response, although evidence for effectiveness is limited.[123][124]

epilepsy syndromes with onset at a variable age

epilepsy with generalized tonic-clonic seizures alone (GTCA)

1st line – anticonvulsants

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1st line –

anticonvulsants

Age at onset is typically between 10 and 25 years (range 5-40 years).[7]

First-line treatment is valproic acid.[115] Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

One Cochrane review supports the use of lamotrigine and levetiracetam as suitable alternatives to valproic acid, particularly for patients of childbearing potential, for whom valproic acid may not be an appropriate therapy due to teratogenicity.[115] [ ] Lamotrigine is also effective as an adjunctive therapy in controlling primary generalized tonic-clonic seizures.[127] Lamotrigine may cause serious and life-threatening dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

Clobazam and topiramate (monotherapy or with valproic acid) are also effective options.[128][129][130]

Perampanel is well tolerated and improves control of drug-resistant primary generalized tonic-clonic seizures in idiopathic generalized epilepsy when used adjunctively in patients ages 12 years or older.[119][141] Perampanel may cause severe psychiatric and behavioral reactions (e.g., aggression, hostility, homicidal ideation); monitor patients closely during dose titration and at higher doses.

Carbamazepine may aggravate seizures in patients with idiopathic generalized epilepsies and so is not recommended.[27]

For patients with the potential to become pregnant, see "Considerations for patients of childbearing potential" in Management approach.

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

Secondary options

lamotrigine: consult specialist for guidance on dose

Tertiary options

topiramate: children ≥2 years of age: 1-3 mg/kg orally (immediate-release) once daily initially, increase gradually according to response, maximum 9 mg/kg/day or 400 mg/day

perampanel: children ≥12 years of age: 2-4 mg orally once daily at bedtime initially, increase gradually according to response, maximum 12 mg/day

Consider – lifestyle modifications

Back

Consider –

lifestyle modifications

Treatment recommended for SOME patients in selected patient group

Lifestyle changes may need to be implemented to achieve freedom from seizures.

Patients should be warned of common seizure precipitants, including sleep deprivation with early waking and alcohol consumption.[126]

2nd line – vagus nerve stimulation or ketogenic diet

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2nd line –

vagus nerve stimulation or ketogenic diet

Vagus nerve stimulation and ketogenic diets are treatment options for patients with drug-resistant idiopathic generalized epilepsy.[60][63][132] Use of a ketogenic diet requires a skilled team including a dietitian, and regular monitoring.[62][63]

Consider – lifestyle modifications

Back

Consider –

lifestyle modifications

Treatment recommended for SOME patients in selected patient group

Lifestyle changes may need to be implemented to achieve freedom from seizures.

Patients should be warned of common seizure precipitants, including sleep deprivation with early waking and alcohol consumption.[126]

juvenile myoclonic epilepsy (JME)

1st line – anticonvulsants

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1st line –

anticonvulsants

Age at onset is typically between 10 and 24 years (range 8-40 years).[7]

First-line option is valproic acid.[115] It may be used alone or in combination with lamotrigine in resistant cases.[115][133] Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

Levetiracetam is considered the most safe and efficacious of the newer anticonvulsants when used as monotherapy.[134][135][136]

Monotherapy with lamotrigine is controversial as, despite its efficacy in controlling tonic-clonic seizures and absences, there is a very high risk of aggravation of myoclonic jerks.[137] Lamotrigine may cause serious and life-threatening dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

Additional treatment options include topiramate, zonisamide, and perampanel.[119][138][139] Perampanel may cause severe psychiatric and behavioral reactions (e.g., aggression, hostility, homicidal ideation); monitor patients closely during dose titration and at higher doses.

Carbamazepine may aggravate seizures in patients with idiopathic generalized epilepsies and so is not recommended.[27]

For patients with the potential to become pregnant, see "Considerations for patients of childbearing potential" in Management approach.

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

Secondary options

lamotrigine: consult specialist for guidance on dose

levetiracetam: children 1-12 years of age: consult specialist for guidance on dose; children ≥12 years of age: 500 mg orally (immediate-release)/intravenously twice daily initially, increase gradually according to response, maximum 3000 mg/day

Tertiary options

topiramate: children ≥2 years of age: 1-3 mg/kg orally (immediate-release) once daily initially, increase gradually according to response, maximum 9 mg/kg/day or 400 mg/day

perampanel: children ≥12 years of age: 2-4 mg orally once daily at bedtime initially, increase gradually according to response, maximum 12 mg/day

Consider – lifestyle modifications

Back

Consider –

lifestyle modifications

Treatment recommended for SOME patients in selected patient group

Lifestyle changes may need to be implemented to achieve freedom from seizures.

Patients should be warned of common seizure precipitants, including sleep deprivation with early waking and alcohol consumption.[126]

juvenile absence epilepsy (JAE)

1st line – anticonvulsants

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1st line –

anticonvulsants

Age at onset is typically between 9 and 13 years (range 8-20 years).[7]

First-line anticonvulsant is ethosuximide for patients with absence seizures only. If seizures persist with ethosuximide or if there are generalized tonic-clonic seizures, valproic acid is preferred.[115][140] Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

Additional treatment options include clobazam, topiramate, zonisamide, and perampanel.[119][140][141] Perampanel may cause severe psychiatric and behavioral reactions (e.g., aggression, hostility, homicidal ideation); monitor patients closely during dose titration and at higher doses.

For patients with the potential to become pregnant, see "Considerations for patients of childbearing potential" in Management approach.

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

Secondary options

lamotrigine: consult specialist for guidance on dose

Tertiary options

topiramate: children ≥2 years of age: 1-3 mg/kg orally (immediate-release) once daily initially, increase gradually according to response, maximum 9 mg/kg/day or 400 mg/day

perampanel: children ≥12 years of age: 2-4 mg orally once daily at bedtime initially, increase gradually according to response, maximum 12 mg/day

Consider – lifestyle modifications

Back

Consider –

lifestyle modifications

Treatment recommended for SOME patients in selected patient group

Lifestyle changes may need to be implemented to achieve freedom from seizures.

Patients should be warned of common seizure precipitants, including sleep deprivation with early waking and alcohol consumption.[126]

unidentified epilepsy syndrome

1st line – anticonvulsants

Back

1st line –

anticonvulsants

Sometimes an epileptic syndrome cannot be diagnosed. Anticonvulsant therapy must be tailored to the individual patient, and is based on seizure types, age, sex, and comorbidities. Monotherapy is preferable, although polypharmacy may be required for seizure control if monotherapy is insufficiently effective. A careful balance of seizure control and anticonvulsant adverse effects should be maintained.[47]

If seizures are generalized or it is not known whether they are focal or generalized, broad-spectrum anticonvulsants are recommended. First-line options include valproic acid, lamotrigine, levetiracetam, and topiramate.

Valproic acid is better tolerated than topiramate and more efficacious than lamotrigine, and remains the drug of choice for many patients with generalized and unclassified epilepsies.[142] Valproic acid may cause serious or fatal hepatic failure (children <2 years of age are at increased risk); hepatic function testing should be performed before and during treatment. Valproic acid may also cause life-threatening pancreatitis.

Lamotrigine is also effective as an adjunctive therapy in combination with other anticonvulsants in controlling primary generalized tonic-clonic seizures.[127][133] Lamotrigine may cause serious and life-threatening dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

Topiramate is well tolerated and effective for prolonged tonic-clonic seizures when used adjunctively with another anticonvulsant, or for resistant tonic-clonic seizures when used as monotherapy.[143][144]

Carbamazepine is indicated for generalized tonic-clonic seizures, but can aggravate absence, myoclonic, and tonic/atonic seizures.[145] Carbamazepine may cause serious and life-threatening dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), particularly in patients with the HLA-B*1502 allele (which is found mainly in Asian patients). Testing for HLA-B*1502 is recommended in patients with genetically at-risk ancestry before starting treatment. Carbamazepine may cause aplastic anemia or agranulocytosis, and hematologic testing should be performed before and during treatment.

For patients with the potential to become pregnant, see "Considerations for patients of childbearing potential" in Management approach.

Primary options

valproic acid: 10-15 mg/kg/day orally given in 1-3 divided doses initially, increase gradually according to response, maximum 60 mg/kg/day

lamotrigine: consult specialist for guidance on dose

topiramate: children ≥2 years of age: 1-3 mg/kg orally (immediate-release) once daily initially, increase gradually according to response, maximum 9 mg/kg/day or 400 mg/day

Secondary options

carbamazepine: children <6 years of age: 10-20 mg/kg/day orally (immediate-release) given in 2-4 divided doses initially, increase gradually according to response, maximum 35 mg/kg/day; children 6-12 years of age: 100 mg orally (immediate-release) twice daily initially, increase gradually according to response, maximum 1000 mg/day given in 2-4 divided doses; children ≥12 years of age: 200 mg orally (immediate-release) twice daily initially, increase gradually according to response, maximum 1200 mg/day given in 2-4 divided doses

Tertiary options

perampanel: children ≥12 years of age: 2-4 mg orally once daily at bedtime initially, increase gradually according to response, maximum 12 mg/day

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Generalized seizures in children

Treatment algorithm

acute repetitive seizures (children >1 month of age)

benzodiazepine

Primary options

Secondary options

parenteral benzodiazepine or anticonvulsant

Primary options

Secondary options

epilepsy syndromes with onset in infancy (1 month to 2 years)

pyridoxine and/or anticonvulsants

Primary options

Secondary options

ketogenic diet or surgery

corticosteroid or corticotropin (ACTH) or vigabatrin

Primary options

Secondary options

alternative anticonvulsants or ketogenic diet or surgery

anticonvulsants

Primary options

Secondary options

anticonvulsants

Primary options

Secondary options

Tertiary options

topiramate

Primary options

ketogenic diet

vagus nerve stimulation

anticonvulsants

Primary options

epilepsy syndromes with onset in childhood (2-12 years)

anticonvulsant and/or ketogenic diet

Primary options

alternative anticonvulsants

Primary options

Secondary options

vagus nerve stimulation or corpus callosotomy

anticonvulsants

Primary options

Secondary options

Tertiary options

corticotropin (ACTH) and/or corticosteroid

nonpharmacologic therapies

anticonvulsants

Primary options

Secondary options

Tertiary options

anticonvulsants

Primary options

anticonvulsants

Primary options

Secondary options

lens therapy

alternative anticonvulsants and/or ketogenic diet

lens therapy

epilepsy syndromes with onset at a variable age

anticonvulsants

Primary options

Secondary options

Tertiary options

lifestyle modifications

vagus nerve stimulation or ketogenic diet

lifestyle modifications

anticonvulsants

Primary options

Secondary options

Tertiary options

lifestyle modifications

anticonvulsants

Primary options

Secondary options

Tertiary options

lifestyle modifications

unidentified epilepsy syndrome

anticonvulsants

Primary options

Secondary options

Tertiary options