Generalized seizures in children

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

Management for the prevention of seizures depends on the epilepsy syndrome, as defined by the International League Against Epilepsy (ILAE).[1][3][7][32][33] Management of the more common epilepsy syndromes with predominantly generalized-onset seizures recognized in childhood will be discussed here. Sometimes the specific epilepsy syndrome cannot be diagnosed, but the patient will still require treatment.

Treatment should be managed initially by a neurologist trained in epilepsy.[27] Epilepsy may worsen the quality of life of a child and family, causing serious hazards including physical injury and sudden death, and influence social aspects of everyday life. Even if epilepsy is successfully treated, some children may still have an impaired quality of life in relation to their own self-esteem, epilepsy comorbidities, and adverse effects associated with therapy.

The main treatment options include anticonvulsant drugs, nondrug therapies such as ketogenic diets and vagus nerve stimulation, and lifestyle measures (i.e., avoiding any precipitating stimuli such as sleep deprivation and alcohol consumption). In children with drug-resistant epilepsies, referral to an epilepsy surgery center is advised for further evaluation and consideration of treatment options, even in the absence of clear localization of seizures on video electroencephalogram (EEG) or on structural imaging.[40][41]

Acute management of status epilepticus (defined as either 5 minutes or more of continuous seizure activity, or two or more discrete seizures between which there is incomplete recovery of consciousness) is beyond the scope of this topic. See Status epilepticus.

Management of acute repetitive seizures

Acute repetitive seizures (also known as seizure clusters) affect up to half of patients with epilepsy, and can significantly disrupt patients' lives, but their prevalence is underappreciated and seizure action plans are often lacking.[42][43]

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]

When a convulsive seizure starts in a child, the child 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]

In a hospital setting, parenteral benzodiazepines (e.g., diazepam, lorazepam) or intravenous formulations of anticonvulsants such as phenytoin (or fosphenytoin), valproic acid, levetiracetam, lacosamide, phenobarbital, 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.

Anticonvulsant drugs: principles of treatment

Anticonvulsants are the first-line treatment for most epilepsy syndromes and are used long term for prevention of seizures. Long-term therapy is indicated only when attacks are of a true epileptic nature and not a manifestation of another treatable disease process. Incorrect diagnosis leads to inadequate and potentially harmful treatment.

The main goal of treatment is to prevent further seizures. Where possible, diagnosis of a specific epilepsy syndrome or underlying cause aids choice of anticonvulsant and guides length of treatment. Drug treatment is usually started after the second unprovoked seizure.[45]

Choice of anticonvulsant is an important decision. Choice should be individualized, taking into account efficacy in a specific syndrome and potential adverse effects. Studies have shown that only a few drugs can control idiopathic generalized epilepsies without potentially causing seizure aggravation.[46]

Monotherapy is preferred, as it decreases the risk of adverse effects and drug interactions, and allows the physician to find the right balance between symptom control and toxicity.[47] However, some of the described syndromes often fail to respond to monotherapy, and combination therapy is required. In these situations, it is important to take into account any interactions between the chosen anticonvulsants, as well as any interactions with other drugs the patient may be taking. The dose of certain anticonvulsants needs to be adjusted according to serum drug levels.

Anticonvulsant drugs may be associated with a small increased risk of suicidal thoughts and behavior. People with epilepsy are also at higher risk of mood and anxiety disorders and suicidal ideation at the time of diagnosis, before starting anticonvulsant medications, and risk of suicide associated with these medications is much lower than the risk of harm due to stopping medications or not starting them.[48][49]

Considerations for patients of childbearing potential

Patients with the potential to become pregnant should be provided with information from early adolescence about the risk of unplanned pregnancy, contraceptive options, and potential adverse pregnancy outcomes. Anticonvulsants with enzyme-inducing properties can lower contraceptive efficacy and lead to an increased failure rate.[50]

For patients of childbearing potential, the safety of anticonvulsants in pregnancy must be taken into account in choice of medication.

Valproic acid and its analogs

In both the US and Europe, valproic acid and its analogs are contraindicated during pregnancy due to the risk of congenital malformations and developmental problems in the child. If it is not possible to stop valproic acid, treatment may be continued with appropriate specialist care. Valproic acid and its analogs must not be used in patients of childbearing potential unless there is a pregnancy prevention program in place and certain conditions are met.[51] If the patient is taking the drug to prevent major seizures and is planning to become pregnant, the decision of continuing valproic acid versus changing to an alternate agent should be made on an individual basis.

Safety of other anticonvulsants

A review of the safety of anticonvulsants (other than valproic acid) in pregnancy by the UK Medicines and Healthcare products Regulatory Agency (MHRA) concluded that lamotrigine and levetiracetam, at maintenance doses, are not associated with an increased risk of major congenital malformations. Available studies also do not suggest an increased risk of neurodevelopmental disorders or delay associated with in-utero exposure to lamotrigine or levetiracetam, but data are more limited.[52] A later study suggested an association between prenatal exposure to levetiracetam and ADHD.[53]

Data for other drugs show an increased risk of major congenital malformations associated with carbamazepine, phenobarbital, phenytoin, and topiramate; possible adverse effects on neurodevelopment of children exposed in utero to phenobarbital and phenytoin; and an increased risk of fetal growth restriction associated with phenobarbital, topiramate, and zonisamide. Risks associated with other anticonvulsants are uncertain due to limitations in the data.[52][54][55] One subsequent MHRA study suggested that pregabalin might slightly increase the risk of major congenital malformations.[56] One large cohort study reported an association between prenatal exposure to topiramate and increased risk of child neurodevelopmental disorders; the use of topiramate in patients of childbearing potential is being reviewed by the European Medicines Agency (EMA) and the MHRA.[57][58][59] One systematic review reported adverse fetal and neonatal outcomes following in-utero exposure to oxcarbazepine.[54]

Nonpharmacologic treatment options

Nonpharmacologic treatment options may need to be explored, especially for refractory epilepsy.[41][60][61][62][63] Referral to an epilepsy surgery center is advised for further evaluation and consideration of treatment options.[40][41] Surgery is only rarely recommended for patients with generalized-onset seizures.

Ketogenic diets

Ketogenic diets are high in fat and low in carbohydrates, and have been demonstrated to be effective in reducing seizure frequency in children with drug-resistant epilepsy. A ketogenic diet should be considered after two anticonvulsant drugs have proved ineffective, and even earlier for several epilepsy syndromes. There are four main types of ketogenic diet (the "classic" ketogenic diet, the modified Atkins diet, the medium chain triglyceride diet, and the low glycemic index treatment), and choice should be individualized, taking into account the situation of the family and child and the expertise of the clinical team. Use of a ketogenic diet requires a skilled team, including a dietitian. The classic ketogenic diet is usually started in the hospital, under close medical supervision, and regular monitoring is required.[41][62][63]

Vagus nerve stimulation

Vagus nerve stimulation is an effective and safe adjunctive therapy in patients with medically refractory epilepsy not amenable to resection. However, some patients do not receive any benefit from this therapy. Common adverse effects include local skin irritation, headache, nasopharyngitis, and voice alteration. Children should be carefully monitored for site infection.[64][65][66][67]

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

Early infantile developmental and epileptic encephalopathy (EIDEE):

This condition is a severe, very difficult to treat epileptic encephalopathy with potential metabolic, genetic, and structural etiologies.
Recognition of metabolic causes of EIDEE is essential to initiate appropriate treatment, if available, and prevent long-term sequelae. However, treatment should not be withheld while waiting for test results.
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 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]
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]
Ketogenic diets should be considered for patients with refractory epilepsy.[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):

Epileptic spasms are resistant to most anticonvulsants. An oral corticosteroid, corticotropin (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 for IESS: 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]
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 EEG.
If the first treatment is ineffective, an alternative medication from the initial options with 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]
There is insufficient evidence for efficacy of other anticonvulsants for the treatment of refractory infantile spasms. Medication choices should be made on an individual patient-specific basis. 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 of a ketogenic diet is reserved for hormone-resistant cases.
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 for surgery, 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):

Seizure control is usually favorable, with patients who show a quick response appearing to have a better outcome.
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.
Other treatment options include topiramate, lamotrigine, clonazepam, and levetiracetam.[69]
There is a suggestion that delays in the start of treatment may cause cognitive problems later in life.[89]
Some patients originally diagnosed with MEI may develop other types of epilepsy, particularly juvenile myoclonic epilepsy.[32]

Dravet syndrome:

Valproic acid and clobazam are recommended as initial therapies.[21][90][91]
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 as adjunctive therapy (with clobazam) for Dravet syndrome in children from age 6 months.[21][91][92]
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]
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 other 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]
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]
Topiramate may be used as monotherapy or adjunctively. Efficacy of topiramate when used as adjunctive therapy for Dravet syndrome has been reported.[21][98]
Ketogenic diets are effective, and should be considered after two unsuccessful anticonvulsant trials, or earlier in some cases.[21][63]
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+), which includes febrile seizures plus (FS+)

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

Management of epilepsy syndromes with onset in childhood

Childhood is defined as ages 2-12 years.[33]

Epilepsy with myoclonic-atonic seizures (EMAtS; also known as Doose syndrome):

Approximately one third of children show a response to anticonvulsants, and less than 10% are seizure-free after anticonvulsant treatment.[99] Valproic acid is recommended most often as first-line therapy.[100][101]
Ketogenic diets are highly effective for this syndrome.[63][99][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]
Options for second-line treatment 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]
Vigabatrin and sodium-channel-blocking drugs other than lamotrigine should be avoided.[101]
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):

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. 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] [ ]
Cannabidiol oral solution is approved for the treatment of seizures associated with LGS for patients ages 1 year and older (2 years and older in some other 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]
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]
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]
Carbamazepine, eslicarbazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, and vigabatrin may exacerbate seizures associated with LGS, and so are usually avoided.[105]
Corticosteroids and/or corticotropin (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).
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]

Childhood absence epilepsy (CAE):

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]
One Cochrane review supports the use of lamotrigine and levetiracetam as suitable alternatives to valproic acid, particularly for patients of childbearing potential for whom valproate (valproic acid in the US) 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]
Topiramate, benzodiazepines, perampanel, and zonisamide are further options.[118][119][120]
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]

Epilepsy with myoclonic absence (EMA):

EMA is often refractory to anticonvulsants, and polypharmacy may be required.
Anticonvulsants commonly used include valproic acid, ethosuximide, lamotrigine, levetiracetam, and benzodiazepines.[115][122] [ ]

Epilepsy with eyelid myoclonia (EEM):

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][123]
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]
There is some evidence for effectiveness of ethosuximide and clobazam.[123][124]
Other anticonvulsants (e.g., topiramate, brivaracetam, zonisamide, cannabidiol, fenfluramine, clonazepam, perampanel, lacosamide, and acetazolamide) may be tried, but there is little evidence for effectiveness in EEM and no consensus about their use.[123][124]
Cannabidiol can also 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]
Lens therapy may be trialed for patients with a photoparoxysmal response, although evidence for effectiveness is limited.[123][124]

Management of epilepsy syndromes with onset at a variable age

Onset of these syndromes often occurs in late childhood/adolescence (from 10 years of age).[7]

See also "Considerations for patients of childbearing potential."

Epilepsy with generalized tonic-clonic seizures alone (GTCA):

Lifestyle measures may need to be implemented to achieve freedom from seizures. Patients should be warned of common seizure precipitants including sleep deprivation and alcohol consumption.[126]
First-line treatment is valproic acid.[115]
One Cochrane review supports the use of lamotrigine and levetiracetam as suitable alternatives to valproic acid, particularly for patients of childbearing potential for whom valproate (valproic acid in the US) 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]
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][131]
Carbamazepine may aggravate seizures in patients with idiopathic generalized epilepsies and so is not recommended.[27]
Vagus nerve stimulation and ketogenic diets are treatment options for patients with drug-resistant idiopathic generalized epilepsy.[61][63][132]

Juvenile myoclonic epilepsy (JME):

Lifestyle adjustments (avoiding sleep deprivation and alcohol consumption) and lifelong anticonvulsant therapy are required in these patients.[126]
First-line option is valproic acid. It may be used alone, or in combination with lamotrigine in resistant cases.[115][133]
One Cochrane review supports the use of lamotrigine and levetiracetam as suitable alternatives to valproic acid, particularly for patients of childbearing potential for whom valproate (valproic acid in the US) may not be an appropriate therapy due to teratogenicity.[115] [ ]
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]
Additional treatment options include topiramate, zonisamide, and perampanel.[119][138][139]
Carbamazepine may aggravate seizures in patients with idiopathic generalized epilepsies and so is not recommended.[27]

Juvenile absence epilepsy (JAE):

JAE is more likely to result in tonic-clonic seizures and is less likely to be outgrown than childhood absence epilepsy.
Lifestyle adjustments (avoiding sleep deprivation and alcohol consumption) and lifelong anticonvulsant therapy are required in these patients.[126]
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]
One Cochrane review supports the use of lamotrigine and levetiracetam as suitable alternatives to valproic acid, particularly for patients of childbearing potential for whom valproate (valproic acid in the US) may not be an appropriate therapy due to teratogenicity.[115] [ ]
Additional treatment options include clobazam, topiramate, zonisamide, and perampanel.[119][140][141]

Unidentified epilepsy syndrome

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.

If seizures are generalized in onset, or it is not known whether onset is 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]

Lamotrigine is also effective as an adjunctive therapy in combination with other anticonvulsants in controlling primary generalized tonic-clonic seizures.[127][133]

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]

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]

Drug discontinuation

Seizure freedom for long periods of time can occur with anticonvulsant therapy or after surgical treatment. Patients taking anticonvulsants who achieve seizure freedom may eventually wish to discontinue medication to avoid the adverse effects, psychological implications, and cost of ongoing treatment.

For children who have been seizure-free for at least 18-24 months, and who do not have an electroclinical syndrome suggesting otherwise, discontinuation of anticonvulsant medication may be considered, as this does not clearly increase risk of seizure recurrence. The risks and benefits of discontinuation should be discussed with the patient and family, and the known natural history of the specific electroclinical syndrome should be taken into account. Provided that an EEG does not show epileptiform activity, discontinuation should be offered at a rate no faster than 25% every 10-14 days.[146]

Syndromes known to have a high risk of relapse are those with a proven/probable lesional origin (Lennox-Gastaut syndrome, severe myoclonic epilepsy, juvenile myoclonic epilepsy, and awakening generalized tonic-clonic seizures). In these cases, prolonged therapy for up to 5 years, or even lifelong therapy, may be required.

There is little evidence to guide the rate of withdrawal of anticonvulsants.[147]

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