Epilepsy

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    Last updated: October 2024

     

    Epilepsy is a chronic neurological disorder characterized by recurrent seizures.

     

    People with epilepsy frequently face discrimination and stigma as well as social and economic difficulties. They are also at risk of mental, behavioural or cognitive disorders as well as seizure-related injuries. Management of comorbidities and patient/family education and support are essential.

     

    Seizures are usually short episodes. A seizure lasting longer than 5 minutes (or 2 or more seizures in 5 minutes without complete restoration of baseline consciousness between seizures) is a medical emergency, see Generalised tonic-clonic seizures and convulsive status epilepticus, Chapter 1.

    Clinical features

    Manifestations of epilepsy (i.e. seizures) are varied. It is critical to recognize the type of seizure to determine patient management.

    Seizures are classified as follows [1] Citation 1. Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):522-530. 
    https://doi.org/10.1111/epi.13670         :

     

    Generalized onset seizures

    • Tonic-clonic seizures: contraction of muscles, including respiratory muscles (tonic phase), followed by rhythmic jerking of the arms and legs (clonic phase) and loss of consciousness;
    • Myoclonic seizures: sudden and brief contractions of a muscle or group of muscles;
    • Atonic seizures: sudden loss of muscle tone, frequently resulting in falls;
    • Absence seizures: brief (a few seconds) impairment of consciousness and cessation of activity; most common in children from 4 years of age.

     

    Focal onset seizures

    • Start with localised symptoms (e.g. jerking movements of one body part or repetitive lips smacking) and sometimes spread to the rest of the body, becoming generalised.

     

    Epilepsy is clinically diagnosed when 2 or more "unprovoked" seizures (i.e. seizures not caused by a temporary reversible condition) of any type occur more than 24 hours apart [2] Citation 2. World Health Organization. Pocket book of primary health care for children and adolescents: guidelines for health promotion, disease prevention and management from the newborn period to adolescence. Copenhagen: WHO Regional Office for Europe; 2022.
    https://www.who.int/europe/publications/i/item/9789289057622         [3] Citation 3. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-482.
    https://doi.org/10.1111/epi.12550         .

    Treatment principles

    • Once the diagnosis of epilepsy (or seizures requiring long-term treatment) has been made, an antiseizure medication (ASM) is prescribed to prevent the occurrence of new seizures.
    • The treatment prescribed should be a monotherapy (i.e. a single ASM).
    • For choosing an ASM, see Choice of an antiseizure medication. The likelihood of continued ASM availability should also be considered when making the choice.
    • Treatment should be taken daily without interruption for the long term. Abruptly stopping or reducing an ASM dose is likely to provoke seizures.
    • Long-term patient follow-up is required, see Patient follow-up. Any change in treatment (dose increments, ASM substitution or discontinuation) requires close clinical monitoring.

    Rarely, ASMs may cause a paradoxical increase in seizure frequency, mainly at the start of treatment or after an increase in dose.

    • If seizures are not controlled, assess adherence to treatment, consider increasing the dose if tolerated, up to the maximum dose if necessary.
    • If seizures are still not controlled or treatment is not tolerated, gradually change to another ASM (slowly increase the dose of the new ASM then slowly decrease the dose of the first ASM until complete substitution).
    • Combination therapy should be considered only if two different ASMs used in monotherapy have failed.
    • Stopping an antiseizure treatment may be considered when the patient has been seizure-free for at least 2 years [4] Citation 4. World Health Organization. mhGAP Intervention Guide for Mental, Neurological and Substance Use Disorders in Non-Specialized Health Settings: Mental Health Gap Action Programme (mhGAP). version 2.0. World Health Organization; 2016. 
      https://www.who.int/publications/i/item/9789241549790             . The benefits/risks of stopping the ASM should be discussed with the patient (seizures may recur after stopping treatment). The dose should be slowly tapered (e.g. by 10% every 2 weeks) over a period of at least 3 months. Patients should seek medical attention if seizures recur during or after stopping treatment.
    • Patient and family education is essential.  Provide information about epilepsy as a disease, the benefits of treatment, ways to maximize control (including adherence to treatment) and first aid for seizures. Explain that people with epilepsy can lead normal lives when certain safety measures are taken (e.g. not swimming alone, not cooking over open flames) [4] Citation 4. World Health Organization. mhGAP Intervention Guide for Mental, Neurological and Substance Use Disorders in Non-Specialized Health Settings: Mental Health Gap Action Programme (mhGAP). version 2.0. World Health Organization; 2016. 
      https://www.who.int/publications/i/item/9789241549790             [5] Citation 5. NICE. Epilepsies in children, young people and adults. Published online April 27, 2022.
      https://www.nice.org.uk/guidance/ng217             .

    Choice of an antiseizure medication

    An ASM is selected according to:

    • the type of seizure: some ASMs may exacerbate some symptoms, 
    • the patient’s characteristics: age, sex, pregnancy or breastfeeding status, comorbidities, and related treatments,
    • the ASM’s adverse effect profile: in general, newer ASMs (e.g. levetiracetam) are safer, better tolerated, and have fewer drug interactions than older ASMs (e.g. carbamazepine, phenobarbital, phenytoin, valproic acid).

     

    Age/Type of seizures

    First choice

    Second choice

    Third choice

    Children 1 month to < 2 years

    Motor, generalised

    (tonic-clonic, myoclonic (a) Citation a. For myoclonic seizures: CBZ and PHT are not recommended (risk of worsening symptoms). , atonic (b) Citation b. For atonic seizures: CBZ is not recommended (risk of worsening symptoms). )

    levetiracetam (LEV)

    phenobarbital (PB)

    carbamazepine (CBZ)

    or phenytoin (PHT)

    Non-motor, generalised (absence)

    –

    –

    –

    Focal (partial)

    LEV or CBZ

    PB or PHT

    –

    Girls 2 to < 10 years, boys ≥ 2 years and men

    Motor, generalised

    (tonic-clonic, myoclonic (a) Citation a. For myoclonic seizures: CBZ and PHT are not recommended (risk of worsening symptoms). , atonic (b) Citation b. For atonic seizures: CBZ is not recommended (risk of worsening symptoms). )

    LEV or

    valproic acid (VPA)

    CBZ or PB

    or PHT

    –

    Non-motor, generalised (absence (c) Citation c. For absence seizures: CBZ, PB and PHT are not recommended (risk of worsening symptoms). )

    LEV or VPA

    –

    –

    Focal (partial)

    LEV or CBZ

    VPA

    PB or PHT

    Girls ≥ 10 years and women

    Motor, generalised

    (tonic-clonic, myoclonics (a) Citation a. For myoclonic seizures: CBZ and PHT are not recommended (risk of worsening symptoms). , atonic (b) Citation b. For atonic seizures: CBZ is not recommended (risk of worsening symptoms). )

    LEV

    CBZ or PHT

    PB

    Non-motoras, generalised (absence (c) Citation c. For absence seizures: CBZ, PB and PHT are not recommended (risk of worsening symptoms). )

    LEV

    –

    –

    Focal (partial)

    LEV

    CBZ or PHT

    PB

    Children

    • VPA is contraindicated in children less than 2 years (increased risk of hepatotoxicity).

    Patients over 65 years

    LEV is preferred in older patients [6] Citation 6. Piccenna L, O’Dwyer R, Leppik I, et al. Management of epilepsy in older adults: A critical review by the ILAE Task Force on Epilepsy in the elderly. Epilepsia. 2023;64(3):567-585. 
    https://doi.org/10.1111/epi.17426         .

    Pregnant women and girls

     

    In all cases:

    • The parents should be informed of current knowledge in terms of risks for the unborn child, in particular when the risk of foetotoxicity is high.
    • Administer the lower effective dose (foetal harms are mainly dose-dependent).
    • ASM plasma concentrations may decrease during pregnancy. If the dose needs to be increased antepartum, start reducing it from D3-D4 postpartum to gradually return to the dose effective before pregnancy.
    • Start taking high dose folic acid to reduce the risk of MCM (5 mg daily for the first trimester [9] Citation 9. Royal College of Obstetricians and Gynaecologists (UK). Epilepsy in Pregnancy. Published online June 2016. https://www.rcog.org.uk/media/rzldnacf/gtg68_epilepsy.pdf a Citation a. The optimal dose of folic acid to prevent MCM is not established. After the first trimester, the dose should be reduced (use the fixed-dose combination 60 mg of elemental iron/400 micrograms folic acid). ).
    • After pregnancy, the benefits of breastfeeding are considered to outweigh the risk of adverse effects of ASMs [10] Citation 10. Pennell PB. Use of Antiepileptic Drugs During Pregnancy: Evolving Concepts. Neurotherapeutics. 2016 Oct;13(4):811-820.
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081129/             .

    Women and girls of childbearing age

    • The choice of an ASM is based on the same criteria as per pregnant women and girls due to the possibility of undiagnosed or future pregnancies.
    • Preconception and/or contraception counselling should be offered. 
    • If considering pregnancy, depending on the ASM currently taken, consider a safer ASM. 
    • When planning pregnancy, start taking folic acid before conception to reduce the risk of MCM.
    • If no pregnancy is planned, effective contraception should be provided:
    • In situations where VPA would be the only effective option (i.e. after confirmation that other ASMs are ineffective or poorly tolerated), a blood pregnancy test should be performed before starting the treatment, then regularly if the patient is not on effective contraception.
    • If pregnancy occurs, see Pregnant women and girls.

    Dosage of antiseizure medications

    Start with a low dose then increase gradually based on patient's response (seizure control) and tolerance (occurrence of adverse effects). The following doses are given as a guide and should be ajusted individually.

     

    carbamazepine PO:

    • Children 1 month to 11 years: start with 5 mg/kg once daily or 2.5 mg/kg 2 times daily; increase the daily dose by increments of 2.5 to 5 mg/kg every 3 to 7 days, up to 5 mg/kg 2 or 3 times daily if necessary (max. 20 mg/kg daily).
    • Children 12 years and over: start with 100 to 200 mg once daily or 50 to 100 mg 2 times daily; increase the daily dose by increments of 100 to 200 mg every week, up to 200 to 400 mg 2 or 3 times daily if necessary (max. 1800 mg daily).
    • Adults: start with 100 to 200 mg once daily or 50 to 100 mg 2 times daily; increase the daily dose by increments of 100 to 200 mg every week, up to 400 mg 2 or 3 times daily if necessary (max. 2 g daily).

     

    levetiracetam PO:

    • Children 1 to 5 months: start with 7 mg/kg once daily; increase to 7 mg/kg 2 times daily after 2 weeks, then by increments of 7 mg/kg 2 times daily every 2 weeks if necessary (max. 21 mg/kg 2 times daily).
    • Children 6 months to 17 years (< 50 kg): start with 10 mg/kg once daily; increase to 10 mg/kg 2 times daily after 2 weeks, then by increments of 10 mg/kg 2 times daily every 2 weeks if necessary (max. 30 mg/kg 2 times daily).
    • Children 50 kg and over and adult: start with 250 mg 2 times daily; increase to 500 mg 2 times daily after 2 to 4 weeks, then by increments of 500 mg 2 times daily every 2 to 4 weeks if necessary (max. 1.5 g 2 times daily).

     

    phenobarbital PO:

    • Children 1 month to 11 years: start with 2 to 3 mg/kg once daily at bedtime or 1 to 1.5 mg/kg 2 times daily for 2 weeks; increase the daily dose by increments of 1 to 2 mg/kg every week, up to 2 to 6 mg/kg once daily if necessary.
    • Children 12 years and over and adults: start with 1 mg/kg (max. 60 mg) once daily at bedtime for 2 weeks; increase the daily dose by increments of 15 to 30 mg every week, up to 3 mg/kg once daily if needed (max. 180 mg daily).

     

    phenytoin PO:

    • Children 1 month to 11 years: start with 1.5 to 2.5 mg/kg 2 times daily; increase the daily dose by increments of 5 mg/kg every 3 to 4 weeks, up to 2.5 to 5 mg/kg 2 times daily if necessary (max. 7.5 mg/kg 2 times daily or 300 mg daily).
    • Children 12 years and over: start with 75 to 150 mg 2 times daily; increase the daily dose by increments of 25 mg every 3 to 4 weeks, up to 150 to 200 mg 2 times daily if necessary (max. 300 mg 2 times daily).
    • Adults: start with 150 to 300 mg once daily or 75 to 150 mg 2 times daily; increase the daily dose by increments of 50 mg every 3 to 4 weeks, up to 200 to 400 mg once daily or 100 to 250 mg 2 times daily if necessary (max. 400 mg once daily or 300 mg 2 times daily).

     

    valproic acid (sodium valproate) PO:

    • Children 2 to 11 years: start with 10 to 15 mg/kg once daily or 5 to 7.5 mg/kg 2 times daily; increase the daily dose by increments of 5 to 10 mg/kg every week, up to 12.5 to 15 mg/kg 2 times daily if necessary (max. 600 mg 2 times daily).
    • Children 12 years and over and adults: start with 500 to 600 mg once daily; increase the daily dose by increments of 200 mg every 3 days, up to 500 mg to 1 g 2 times daily if necessary (max. 2.5 g daily).

    Patient follow-up

    The initial follow-up schedule is guided by titration of the prescribed ASM.

    Once seizures are controlled for at least 1 month, follow-up can be spaced out to 3 months, then every 6 months if the patient is stable.

     

    Encourage maintaining a seizure diary if possible.

     

    At each consultation:

    • Assess:
      • Growth and development in children.
      • Treatment :
        • response (seizure frequency) and tolerance (adverse effects),
        • impact on daily life (e.g. time off school or work).
      • Adherence to treatment.
      • Co-morbidities, including associated anxiety or depression.
    • Adjust the dose of the ASM if necessary. In this case, review patient as needed but in any case within one month following any change in dose.
    • Provide treatment until the next consultation or the facility’s dispensing schedule.
    • Answer questions, discuss problems, and try to find solutions with the patient.

     

    Footnotes
    • (a)The optimal dose of folic acid to prevent MCM is not established. After the first trimester, the dose should be reduced (use the fixed-dose combination 60 mg of elemental iron/400 micrograms folic acid).
    • (a) For myoclonic seizures: CBZ and PHT are not recommended (risk of worsening symptoms).
    • (b) For atonic seizures: CBZ is not recommended (risk of worsening symptoms).
    • (c) For absence seizures: CBZ, PB and PHT are not recommended (risk of worsening symptoms).
    References
    Path