Anticonvulsants used for Generalised Seizures

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PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

See also: Treatments for Epilepsy written for patients

Other relevant separate articles include Status Epilepticus Management, Epilepsy in Adults, Epilepsy in Children and Young People and Epilepsy in Elderly People.

Generalised seizures are characterised by widespread involvement of bilateral cortical regions at the outset and are usually accompanied by impairment of consciousness:[1][2]

  • The familiar tonic-clonic seizure (grand mal) is often preceded by a cry. The patient suddenly falls to the ground and exhibits typical convulsive movements, sometimes with tongue or mouth biting and urinary incontinence. Other subtypes of generalised seizures include absence, myoclonic, clonic, tonic and atonic seizures.
  • Absence seizures (petit mal) mainly affect children. Typical absence seizures usually last 5-10 seconds and commonly occur in clusters. They manifest as sudden onset of staring and impaired consciousness with or without eye blinking and lip-smacking. The electroencephalograph (EEG) typically shows a 3 Hz spike and wave pattern. There is a strong genetic component for the seizures as well as for the EEG abnormality. While absences will remit during adolescence in around 40% of patients, related tonic-clonic seizures may continue into adulthood.
  • Atypical absence seizures usually begin before 5 years of age in conjunction with other generalised seizure types and general learning disability. They last longer than typical absence seizures and are often associated with changes in muscle tone.
  • Myoclonic seizures consist of sudden, brief muscle contractions, either singly or in clusters, that can affect any muscle group.
  • Clonic seizures are characterised by rhythmic or semi-rhythmic muscle contractions, typically involving the upper extremities, neck and face.
  • Tonic seizures cause sudden stiffening of extensor muscles, often associated with impaired consciousness and falling to the ground.
  • Atonic seizures (drop attacks) produce sudden loss of muscle tone with instantaneous collapse, often resulting in facial or other injuries.

About two in three adults with new-onset epilepsy will achieve lasting seizure remission on or off anti-epileptic drugs (AEDs), although around half will experience mild to moderately severe adverse effects.[3] 

Generalised tonic-clonic (GTC) seizures

  • First-line treatment: offer sodium valproate as first-line treatment. Offer lamotrigine if sodium valproate is unsuitable. If the person has myoclonic seizures or is suspected of having juvenile myoclonic epilepsy (JME), be aware that lamotrigine may exacerbate myoclonic seizures. Consider carbamazepine and oxcarbazepine but be aware of the risk of exacerbating myoclonic or absence seizures.
  • Adjunctive treatment: offer clobazam, lamotrigine, levetiracetam, sodium valproate or topiramate if first-line treatments are ineffective or not tolerated.
  • If there are absence or myoclonic seizures, or if JME is suspected, do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

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Absence seizures

  • First-line treatment: offer ethosuximide or sodium valproate as first-line treatment to children, young people and adults with absence seizures. If there is a high risk of GTC seizures, offer sodium valproate first, unless it is unsuitable. Offer lamotrigine if ethosuximide and sodium valproate are unsuitable, ineffective or not tolerated.
  • Adjunctive treatment: if two first-line AEDs are ineffective, consider a combination of two of these three AEDs as adjunctive treatment: ethosuximide, lamotrigine or sodium valproate.
  • If adjunctive treatment is ineffective or not tolerated, discuss with, or refer to, a tertiary epilepsy specialist and consider clobazam, clonazepam, levetiracetam, topiramate or zonisamide.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Myoclonic seizures

  • First-line treatment: offer sodium valproate as first-line treatment, unless it is unsuitable. Consider levetiracetam or topiramate if sodium valproate is unsuitable or not tolerated. Topiramate has a less favourable side-effect profile than levetiracetam and sodium valproate.
  • Adjunctive treatment: offer levetiracetam, sodium valproate or topiramate if first-line treatments are ineffective or not tolerated.
  • If adjunctive treatment is ineffective or not tolerated, discuss with, or refer to, a tertiary epilepsy specialist and consider clobazam, clonazepam, piracetam or zonisamide.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Tonic or atonic seizures

  • First-line treatment: offer sodium valproate as first-line treatment.
  • Adjunctive treatment: offer lamotrigine as adjunctive treatment if first-line treatment with sodium valproate is ineffective or not tolerated.
  • Discuss with a tertiary epilepsy specialist if adjunctive treatment is ineffective or not tolerated. Other AEDs that may be considered by the tertiary epilepsy specialist are rufinamide and topiramate.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, pregabalin, tiagabine or vigabatrin.

Infantile spasms

See separate West's Syndrome (Infantile Spasms) article.

  • First-line treatment: refer to a tertiary paediatric epilepsy specialist when an infant presents with infantile spasms. Offer a steroid (prednisolone or tetracosactide) or vigabatrin as first-line treatment of infantile spasms that are not due to tuberous sclerosis.
  • Offer vigabatrin as first-line treatment to infants with infantile spasms due to tuberous sclerosis. If vigabatrin is ineffective, offer a steroid (prednisolone or tetracosactide).

Dravet's syndrome (severe myoclonic epilepsy of infancy)[5]

  • First-line treatment: refer to a tertiary paediatric epilepsy specialist. Consider sodium valproate or topiramate as first-line treatment in children with Dravet's syndrome.
  • Adjunctive treatment: discuss with a tertiary epilepsy specialist if first-line treatments are ineffective or not tolerated; consider clobazam or stiripentol as adjunctive treatment.
  • Do not offer carbamazepine, gabapentin, lamotrigine, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Lennox-Gastaut syndrome

See also separate Lennox-Gastaut Syndrome article.

  • First-line treatment: discuss with, or refer to, a tertiary paediatric epilepsy specialist. Offer sodium valproate as first-line treatment.
  • Adjunctive treatment: offer lamotrigine as adjunctive treatment if first-line treatment with sodium valproate is ineffective or not tolerated.
  • Discuss with a tertiary epilepsy specialist if adjunctive treatment is ineffective or not tolerated. Other AEDs that may be considered by the tertiary epilepsy specialist are rufinamide and topiramate.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, pregabalin, tiagabine or vigabatrin.

Benign epilepsy with centrotemporal spikes, Panayiotopoulos syndrome or late-onset childhood occipital epilepsy (Gastaut-type)

  • First-line treatment: discuss with the child or young person and their family and/or carers whether AED treatment is indicated. Offer carbamazepine or lamotrigine as first-line treatment. Consider levetiracetam, oxcarbazepine or sodium valproate if carbamazepine and lamotrigine are unsuitable or not tolerated. If the first AED tried is ineffective, offer an alternative from these five AEDs. Carbamazepine and oxcarbazepine may exacerbate or unmask continuous spike and wave during slow sleep, which may occur in some children with benign epilepsy with centrotemporal spikes.
  • Adjunctive treatment: offer carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate or topiramate as adjunctive treatment if first-line treatments are ineffective or not tolerated. If adjunctive treatment is ineffective or not tolerated, discuss with, or refer to, a tertiary epilepsy specialist. Other AEDs that may be considered by the tertiary epilepsy specialist are eslicarbazepine acetate, lacosamide, phenobarbital, phenytoin, pregabalin, tiagabine, vigabatrin and zonisamide.

Idiopathic generalised epilepsy (IGE)

  • First-line treatment: offer sodium valproate as first-line treatment, particularly if there is a photo-paroxysmal response on EEG. Offer lamotrigine if sodium valproate is unsuitable or not tolerated. Lamotrigine can exacerbate myoclonic seizures. Consider topiramate but it has a less favourable side-effect profile than sodium valproate and lamotrigine.
  • Adjunctive treatment: offer lamotrigine, levetiracetam, sodium valproate or topiramate as adjunctive if first-line treatments are ineffective or not tolerated.
  • If adjunctive treatment is ineffective or not tolerated, discuss with, or refer to, a tertiary epilepsy specialist and consider clobazam, clonazepam or zonisamide.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Juvenile myoclonic epilepsy (JME)

  • First-line treatment: offer sodium valproate as first-line treatment unless it is unsuitable. Consider lamotrigine, levetiracetam or topiramate if sodium valproate is unsuitable or not tolerated. Topiramate has a less favourable side-effect profile than lamotrigine, levetiracetam and sodium valproate. Lamotrigine may exacerbate myoclonic seizures.
  • Adjunctive treatment: offer lamotrigine, levetiracetam, sodium valproate or topiramate as adjunctive if first-line treatments are ineffective or not tolerated.
  • If adjunctive treatment is ineffective or not tolerated, discuss with, or refer to, a tertiary epilepsy specialist and consider clobazam, clonazepam or zonisamide.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Epilepsy with generalised tonic-clonic (GTC) seizures only

  • First-line treatment: offer lamotrigine or sodium valproate as first-line treatment. If they have suspected myoclonic seizures, or are suspected of having JME, offer sodium valproate first, unless it is unsuitable. Consider carbamazepine and oxcarbazepine but be aware of the risk of exacerbating myoclonic or absence seizures.
  • Adjunctive treatment: offer clobazam, lamotrigine, levetiracetam, sodium valproate or topiramate as adjunctive treatment if first-line treatments are ineffective or not tolerated.

Childhood absence epilepsy, juvenile absence epilepsy or other absence epilepsy syndromes

  • First-line treatment: offer ethosuximide or sodium valproate as first-line treatment. If there is a high risk of GTC seizures, offer sodium valproate first, unless it is unsuitable. Offer lamotrigine if ethosuximide and sodium valproate are unsuitable, ineffective or not tolerated.
  • Adjunctive treatment: if two first-line AEDs are ineffective or not tolerated, consider a combination of two of ethosuximide, lamotrigine or sodium valproate.
  • If adjunctive treatment is ineffective or not tolerated, discuss with, or refer to, a tertiary epilepsy specialist and consider clobazam, clonazepam, levetiracetam, topiramate or zonisamide.
  • Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Other epilepsy syndromes

Refer to a tertiary paediatric epilepsy specialist all children and young people with continuous spike and wave during slow sleep, Landau-Kleffner syndrome or myoclonic-astatic epilepsy.

  • Interactions between AEDs are complex and may enhance toxicity without a corresponding increase in anti-epileptic effect.
  • Interactions are usually caused by hepatic enzyme induction or hepatic enzyme inhibition; displacement from protein binding sites is not usually a problem.
  • These interactions are very variable and unpredictable.
  • AED therapy should only be started once the diagnosis of epilepsy is confirmed, except in exceptional circumstances. AED therapy should be initiated by a specialist.
  • Treatment with AED therapy is generally recommended after a second epileptic seizure. AED therapy should be considered and discussed after a first unprovoked seizure if:
    • There is a neurological deficit.
    • The EEG shows unequivocal epileptic activity.
    • The patient considers the risk of having a further seizure unacceptable.
    • Brain imaging shows a structural abnormality.
  • The dose of each medication should be titrated slowly to the maximally tolerated dose or the maximum level as recommended in the British National Formulary. The effect may be monitored by patient-recorded seizure frequency.
  • Formulations of AEDs are not interchangeable and generic substitution should not be routinely made. Routine switching between different manufacturers of AEDs should be avoided.
  • Maintain a high level of vigilance for adverse effects of treatment.
  • Continuing AED therapy should be planned by a specialist but part of an agreed treatment plan and the needs of the child, young person or adult and their family and/or carers as appropriate should be taken into account.
  • If management is straightforward, continuing AED therapy can be prescribed in primary care if local circumstances and/or licensing allow.
  • Adherence to treatment can be optimised with the following:
    • Educating children, young people and adults and their families and/or carers in the understanding of their condition and the rationale of treatment.
    • Reducing the stigma associated with the condition.
    • Using simple medication regimens.
    • Positive relationships between healthcare professionals, the child, young person or adult with epilepsy and their family and/or carers.
  • Regular blood test monitoring is not recommended as routine, and should be done only if clinically indicated. Indications for monitoring of AED blood levels are:
    • Detection of non-adherence to the prescribed medication.
    • Suspected toxicity.
    • Adjustment of phenytoin dose.
    • Management of pharmacokinetic interactions (eg, changes in bioavailability, changes in elimination, and co-medication with interacting drugs).
    • Specific clinical conditions - eg, status epilepticus, organ failure and certain situations in pregnancy.
  • Examples of blood tests include:
    • Before surgery - clotting studies in those on sodium valproate.
    • FBC, electrolytes, liver enzymes, vitamin D levels and other tests of bone metabolism (eg, serum calcium and alkaline phosphatase) every 2-5 years for adults taking enzyme-inducing drugs.
    • Asymptomatic minor abnormalities in test results are not necessarily an indication for changes in medication.
  • Drug-resistant epilepsy has been defined as failure to achieve sustained seizure freedom after trials of two tolerated and appropriate AED schedules (as monotherapies or in combination). The majority of patients with newly diagnosed epilepsy respond well to AEDs. Failure to do so may be due to:
    • An incorrect diagnosis of epilepsy.
    • An inappropriate choice of AED for the epilepsy syndrome.
    • Failure to take the prescribed AED.
    • An underlying cerebral neoplasm, metabolic condition or immune process.
    • Concurrent drug or alcohol misuse.
  • Given a correct diagnosis of epilepsy, failure to control seizures completely with the first well-tolerated AED is a predictor of drug-resistant epilepsy. Once two AEDs have failed as monotherapy the chance of seizure freedom with further monotherapy is low.
  • Improvement in seizure control may be obtained by combining AEDs. A range of different AEDs appropriate to the epilepsy syndrome should be added as necessary in sequence, increasing the dose of each slowly to obtain the best response. It may be worthwhile trying the addition of a small dose of a third AED but it may be necessary to accept the persistence of some seizures.
  • For drug-resistant generalised or unclassified epilepsy: lamotrigine, levetiracetam, ethosuximide, sodium valproate and topiramate may be used in the adjunctive treatment of generalised epilepsy.
  • Failure to respond to appropriate AEDs should prompt a review of the diagnosis of epilepsy and adherence to medication.Combination therapy should be considered when treatment with two first-line AEDs has failed or when improved control occurs during the process of phased substitution.
  • The decision to continue or withdraw medication should be taken after a full discussion of the risks and benefits of continuing or withdrawing AED therapy. Withdrawal of AEDs must be managed by, or be under the guidance of, the specialist.
  • The risks and benefits of continuing or withdrawing AED therapy should be discussed when the person with epilepsy has been seizure-free for at least two years.
  • Withdrawal of AED treatment should be carried out slowly (at least 2-3 months) and one drug should be withdrawn at a time.
  • Particular care should be taken when withdrawing benzodiazepines and barbiturates (may take up to six months or longer) because of the possibility of drug-related withdrawal symptoms and/or seizure recurrence.
  • There should be an agreed plan that if seizures recur, the last dose reduction is reversed and medical advice is sought.

Further reading & references

  1. Epilepsy; NICE CKS, December 2014 (UK access only)
  2. Epilepsies: diagnosis and management; NICE Clinical Guideline (January 2012)
  3. Schmidt D, Schachter SC; Drug treatment of epilepsy in adults. BMJ. 2014 Feb 28;348:g254. doi: 10.1136/bmj.g254.
  4. Diagnosis and management of epilepsy in adults; Scottish Intercollegiate Guidelines Network - SIGN (2015)
  5. Catarino CB, Liu JY, Liagkouras I, et al; Dravet syndrome as epileptic encephalopathy: evidence from long-term course and Brain. 2011 Oct;134(Pt 10):2982-3010. Epub 2011 Jun 29.
  6. British National Formulary; NICE Evidence Services (UK access only)

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Colin Tidy
Current Version:
Peer Reviewer:
Prof Cathy Jackson
Document ID:
451 (v9)
Last Checked:
05/06/2015
Next Review:
03/06/2020

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