Note from the Scottish Intercollegiate Guidelines Network (SIGN) and National Guideline Clearinghouse (NGC): In addition to these evidence-based recommendations, the guideline development group also identifies good practice points in the full-text guideline document.
The grades of recommendations (A-D) and levels of evidence (1++, 1+, 1-, 2++, 2+, 2-, 3, 4) are defined at the end of the "Major Recommendations" field.
Who Should Make the Diagnosis of Epilepsy?
C - The diagnosis of epilepsy should be made by an epilepsy specialist.
Definition and Classification
The Relevance of Classification in Clinical Practice
C - The seizure type(s) and epilepsy syndrome should be identified.
C - The distinction should be made between a focal epilepsy and a genetic generalised epilepsy.
Clinical Factors and Diagnosis
C - A clear history from the patient and an eyewitness to the attack give the most important diagnostic information, and should be the mainstay of diagnosis.
Use of Electroencephalography (EEG) in the Diagnosis and Classification of Epilepsy
C - EEG is not routinely indicated and cannot exclude a diagnosis of epilepsy.
C - EEG should be used to support the classification of epileptic seizures and epilepsy syndromes when there is clinical doubt.
C - EEG should be performed in young people with generalised seizures to aid classification and to detect a photoparoxysmal response.
B - Short-term video-EEG, preferably with suggestion, should be available for the investigation and diagnosis of suspected epilepsy and non-epileptic attack disorder.
C - Inpatient video-EEG monitoring and other specialist investigations (including polysomnography with full EEG montages) should be available for patients who present diagnostic difficulties.
C - Magnetic resonance imaging (MRI) is the modality of choice for brain imaging in patients with epilepsy.
C - Brain imaging is not routinely required when there is a confident diagnosis of a genetic generalised epilepsy.
D - Computed tomography (CT) has a role in the urgent assessment of seizures, or when MRI is contraindicated.
When to Start Antiepileptic Treatment
B - The decision to start antiepileptic drugs (AEDs) should be made by the patient and an epilepsy specialist.
AEDs should be offered after a first tonic-clonic seizure if:
- B - The patient has had previous myoclonic, absence or partial seizures
- B - The EEG shows unequivocal epileptic discharges
- B - The patient has a structural cerebral disorder
- D - The patient considers the risk of recurrence unacceptable
Antiepileptic Drug Monotherapy
Choice of Formulation
A - In patients with focal onset seizures, lamotrigine is the drug of choice. Where lamotrigine is poorly tolerated, carbamazepine and levetiracetam may be reasonable alternatives.
A - In genetic generalised epilepsy or unclassified epilepsy, sodium valproate is the most effective antiepileptic drug.
- A - Where sodium valproate is poorly tolerated or contraindicated, lamotrigine and topiramate are suitable alternatives.
- D -In women of childbearing age, levetiracetam or lamotrigine may be a reasonable alternative.
C - Routine switching between different manufacturers of antiepileptic drugs should be avoided.
Management of Drug-resistant Epilepsy
Drug-resistant Generalised or Unclassified Epilepsy
C - Failure to respond to appropriate antiepileptic drugs should prompt a review of the diagnosis of epilepsy and adherence to medication.
D - Combination therapy should be considered when treatment with two first-line antiepileptic drugs has failed or when improved control occurs during the process of phased substitution.
A - Carbamazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, topiramate, sodium valproate and zonisamide may be used in the adjunctive treatment of focal epilepsy.
A - Lamotrigine, levetiracetam, ethosuximide, sodium valproate and topiramate may be used in the adjunctive treatment of generalised epilepsy.
B - The choice of drugs in combination should be matched to the patient's seizure type(s) and should, where possible, be limited to two or at most three antiepileptic drugs.
Antiepileptic Drug Blood Levels
D - Routine monitoring of antiepileptic drug concentrations is not indicated. Measurement can sometimes be useful in the following circumstances:
- Adjustment of phenytoin dose
- Assessment of adherence
- Assessment of toxicity
- Situations where drug metabolism is likely to change, e.g., pregnancy
- Otherwise unexplained loss of seizure control
Management of Provoked Seizures
B - Following an acute brain insult or neurosurgery, long-term prophylactic antiepileptic drug treatment is not indicated.
C - Following an acute brain insult, antiepileptic drugs used to treat the provoked seizures should be withdrawn (unless unprovoked seizures occur later).
D - Antiepileptic drug treatment is not indicated for concussive convulsions.
Antiepileptic Drug Adverse Effects
Chronic Systemic Adverse Effects
C - Patients should be warned of common potential adverse effects and given clear instructions to seek medical attention urgently for symptoms including rash, bruising or somnolence with vomiting especially in the first weeks of treatment.
D - Liver function and full blood count should not be monitored routinely.
C - Patients taking antiepileptic drugs should receive dietary and other lifestyle advice to minimise the risk of osteoporosis.
Psychiatric and Behavioural Adverse Effects of Antiepileptic Drugs
B - The potential negative psychotropic effects of antiepileptic drugs should be borne in mind when deciding on the most appropriate antiepileptic drug treatment for an individual patient.
Antiepileptic Drug Withdrawal
A - Prognostic index indicators can be used to give an estimate of the risks of seizure recurrence following antiepileptic drug withdrawal.
B - Referral for assessment for neurosurgical treatment should be considered if the epilepsy is drug resistant.
D - Assessment as to suitability for a potentially curative resective procedure should be made before consideration of palliative procedures such as vagus nerve stimulation (VNS).
Vagus Nerve Stimulation
C - VNS may be considered in adult patients who have been found to be unsuitable for resective surgery.
Management of Prolonged Seizures Including Status Epilepticus
D - EEG should be used for confirming diagnosis of and monitoring treatment effect in patients with status epilepticus. EEG should be available as an emergency intervention for all patients with treated or suspected status epilepticus.
B - Patients with prolonged tonic-clonic seizures that have lasted five minutes or more should be given:
- Midazolam 10 mg buccally or intranasally, or
- Lorazepam 4 mg intravenously (IV) if midazolam is unavailable, or
- Diazepam 10 mg IV or rectally if midazolam and lorazepam are unavailable
In-Hospital Treatment (Following Failure of Initial Benzodiazepine)
B - Administer a repeat dose of benzodiazepine in hospital after 10 minutes if there is no response.
D - Within 30 minutes, if seizures continue:
- Give sodium valproate 20–30 mg/kg IV 40 mg/min, or phenytoin 18 mg/kg IV 50 mg/min with ECG monitoring. Rates of phenytoin infusion may need to be reduced if hypotension or arrhythmia occur in older people or where there is renal/hepatic impairment.
Seizures Persisting Longer Than 30 Minutes
D - If status persists, then within 60 minutes:
- Admit the patient to an intensive treatment unit and administer general anaesthesia
- Refer for specialist advice
D - EEG should be used to determine response to treatment.
Non-convulsive Status Epilepticus
D - EEG should be used for diagnosing and monitoring treatment response in patients with nonconvulsive status epilepticus.
Patients with Recurrent Prolonged or Serial Seizures in the Community
B - Patients with recurrent prolonged or serial seizures in the community should be initially managed by carers who should give midazolam 10 mg buccally or intranasally, or diazepam 10–20 mg rectally according to an agreed administration protocol.
D - All carers of patients with epilepsy who may require buccal midazolam or rectal diazepam should receive recognised training in its administration.
D - Where a care plan is required, it should be drawn up in consultation with the general practitioner (GP) and/or specialist service, used by everyone working with the individual patient, and reviewed at regular intervals.
Management of Older People with Epilepsy
Antiepileptic Drug Treatment
B - Lamotrigine or possibly levetiracetam should be considered when starting antiepileptic drug treatment in older people with focal-onset seizures.
C - Gabapentin is an alternative mono- or adjunctive therapy option in older people with epilepsy.
Management of People with Learning Disability and Epilepsy
D - People with learning disability should be treated with the same range of antiepileptic drugs as the general population.
Epilepsy and Women's Health
C - To minimise the risk of contraceptive failure, a woman using any combined hormonal contraception, or a combined oral contraceptive pill, or a progesterone-only pill should be prescribed an antiepileptic drug that does not induce hepatic enzymes.
D - For women receiving hepatic enzyme-inducing antiepileptic drugs:
- The levonorgestrel intrauterine system may be used without restriction.
- Depot injections of progestogen may be used without restriction and with no alteration to the normal dosing/replacement interval.
- Progestogen-only oral contraceptives are not recommended.
- Progestogen implants (levonorgestrel and etonogestrel) are not recommended.
- If there is no alternative to a combined oral contraceptive pill (COCP), the COCP should contain at least 50 micrograms daily of oestrogen; if the COCP contains less oestrogen, the woman should be warned that the efficacy is reduced and additional barrier methods should be used.
- If breakthrough bleeding occurs with a COCP containing 50 micrograms of oestrogen, the COCP dose should be increased to a maximum of 70 micrograms and 'tricycling' should be considered.
- If the antiepileptic drug is withdrawn, it is important to note that enzyme induction persists for up to four weeks. Contraceptive cover should be ensured during this time.
D - Women with epilepsy receiving lamotrigine:
- Can use progestogen-only contraceptives without restriction. These women should be made aware of signs and symptoms of lamotrigine toxicity, and have the lamotrigine dose reduced if these occur.
- And combined hormonal contraceptives should be counselled about the reduction in circulating lamotrigine concentrations and the potential for, and consequences of, increased seizure activity. The healthcare professional should also discuss the possibility of increasing the lamotrigine dose with the patient.
- And combined hormonal contraceptives should be warned about signs and symptoms of lamotrigine toxicity if the contraceptive is withdrawn. A reduction in lamotrigine dosing may be necessary at this time.
D - Women with epilepsy who are not taking antiepileptic drugs, or who are taking non-enzyme inducing antiepileptic drugs, including lamotrigine, can use emergency contraception as for the general population.
D - Women with epilepsy who require emergency contraception while using enzyme-inducing antiepileptic drugs, or who have stopped taking these within the last 28 days:
- Should be prescribed a single dose of levonorgestrel 3 mg (as opposed to 1.5 mg), ideally as soon as possible, and within 72 hours of unprotected intercourse
- Should not be offered ulipristal acetate (ellaOne®) because of a risk of reduced efficacy
- May be offered insertion of a non-hormonal intrauterine device within 5 days of intercourse as an alternative option
Women with epilepsy should:
- B - Receive prepregnancy counselling at the time of diagnosis and at regular intervals during their management, especially if they are taking antiepileptic drug treatment
- D - Be reassured that most will have a normal pregnancy and delivery
- C - Have their diagnosis and treatment, if appropriate, reviewed by specialist services before conception; a concerted effort should be made to optimise seizure control and rationalise antiepileptic drug therapy prior to conception
- D - Be well informed about pregnancy and epilepsy-related issues, including smoking cessation, before conception
C - Women with epilepsy trying to conceive or who present in the first trimester should be advised to take folic acid during this time to reduce the risk of major congenital malformations.
D - Women receiving sodium valproate should be advised that folic acid supplementation may reduce the rate of spontaneous miscarriage.
Folic acid dosing:
- 400 micrograms daily for -
- A - Women with epilepsy not receiving antiepileptic drug treatment
- 5 mg daily for -
- D - Women with epilepsy receiving antiepileptic drug treatment
- A - Women with epilepsy not on antiepileptic drug treatment, but with a family history of or a previous child with a neural tube defect
- A - Women with epilepsy not on antiepileptic drug treatment, but with a body mass index (BMI) >30.
Seizure Control During Pregnancy
D - As good seizure control during pregnancy is more likely in women whose seizures are controlled prior to becoming pregnant an effort should be made to optimise seizure control prior to pregnancy (particularly for generalised tonic-clonic seizures).
AED Doses and Blood Level Monitoring During Pregnancy
D - In pregnancy, dosing adjustment for the majority of antiepileptic drugs (with the exception of lamotrigine and levetiracetam) should only be considered if there is a change in seizure frequency or if toxicity is suspected.
D - Healthcare professionals should be aware that the dose of lamotrigine may need to be increased during pregnancy. To avoid postpartum neurotoxicity, the lamotrigine dose should be reduced early in the puerperium.
D - Pregnant women with epilepsy receiving hepatic enzyme-inducing antiepileptic drugs who require antenatal corticosteroids for the prevention of neonatal respiratory morbidity, should receive double the standard dose of betamethasone/dexamethasone (48 mg over 12–24 hours).
D - All infants of women with epilepsy should be offered vitamin K1, 1 mg intramuscularly at birth, unless there are contraindications.
D - If there are additional risk factors for haemorrhagic disease of the newborn (for example maternal liver disease, anticipated premature delivery) consideration should be given to the maternal administration of oral vitamin K1 (phytomenadione 10 mg daily) in the third trimester of pregnancy.
Labour and Birth
D - The usual oral antiepileptic drug should be continued during labour and in the postnatal period. Every effort should be made to ensure that no doses are missed. In women with epilepsy who are unable to tolerate oral medication, the antiepileptic drug can be given by other routes.
Seizures in Labour
D - Intrapartum generalised tonic-clonic seizures that are not due to eclampsia should be terminated as soon as possible.
D - If the seizure persists, this should be managed as for status epilepticus.
Fetal, Neonatal and Childhood Outcomes
Risks to the Fetus from Maternal Seizures
D - Pregnant women with epilepsy should be made aware of the risks of uncontrolled seizures both to themselves and to their developing fetus.
Risks to the Fetus Associated with Antiepileptic Drug Monotherapy
D - Women with epilepsy should be informed that sodium valproate is associated with a higher rate of teratogenicity compared to other antiepileptic drugs.
Risks to the Fetus Associated with Antiepileptic Drug Polytherapy
D - Women with epilepsy should be informed that antiepileptic drug polytherapy regimens including sodium valproate are associated with higher rates of congenital malformations compared to regimens not including sodium valproate.
C - Women with epilepsy should be reassured that antiepileptic drugs do not increase the risk of spontaneous miscarriage and stillbirth.
Advice about Breastfeeding
D - Parents should be made aware of signs of toxicity in infants of breastfeeding women taking antiepileptic drugs. The possibility of sedation should be considered in infants of mothers taking high dose antiepileptic drugs, polytherapy, or regimens including primidone, levetiracetam, gabapentin, lamotrigine and topiramate.
Menopause and Epilepsy
D - Women should be aware that their seizure pattern may change around the menopause.
D - Hormone replacement therapy should be prescribed for the same indications as in women who do not have epilepsy.
D - Screening for depression and suicidality should be considered in all patients with epilepsy.
D - The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Hospital Anxiety and Depression Scale Depression subscale (HADS-D), Beck's Depression Inventory (BDI-II) or Patient Health Questionnaire 2 (PHQ-2) can all be used to screen for depression in adults with depression and epilepsy. The NDDI-E may be superior for detecting severe depression and suicidal ideation.
D - Treatment with antidepressants should be considered in patients with epilepsy and comorbid depression.
Sudden Unexpected Death in Epilepsy (SUDEP)
B - Healthcare professionals and patients should aim for complete seizure freedom to reduce the risk of SUDEP.
D - Adherence to the prescribed antiepileptic drug regime should be strongly encouraged and the patient asked to report any adverse effects that might compromise adherence in order to reduce the risk of increased mortality and morbidity.
Counselling Patients About the Risks of SUDEP
D - Counselling about the risks of SUDEP should be considered for patients with epilepsy at an appropriate time for the patient and by an appropriate healthcare professional (consultant neurologist, physician with an interest in epilepsy, specialist registrar, or epilepsy nurse specialist).
Models of Care
Models of Primary Care for Epilepsy
Regular Structured Review
D - A structured management system for patients with epilepsy should be established in primary care. As with other chronic diseases, an annual review is desirable.
D - The annual review should be facilitated by specialist epilepsy nurses, linking primary care to the hospital system (shared care).
D - The shared care management system adopted should seek to:
- Identify all patients with epilepsy, register/record basic demographic data, validate the classification of seizures and syndromes
- Make the provisional diagnosis in new patients, provide appropriate information and refer the patient to a specialist centre
- Monitor seizures, aiming to improve control by adjustment of medication or re-referral to hospital services
- Minimise the adverse effects of medications and their interactions
- Facilitate structured withdrawal from medication where appropriate, and if agreed by the patient
- Introduce non-clinical interventions, and disseminate information to help improve the quality of life for patients with epilepsy
- Address specific women's issues
- Address the needs of patients with learning disabilities
D - Healthcare professionals who carry out structured primary-care reviews for patients with epilepsy should have attended an epilepsy training course in the past five years or be able to demonstrate equivalent experience from continuing professional development.
D - Patients presenting to primary care with suspected first seizure or new epilepsy should be referred to an epilepsy specialist and asked to take an eyewitness or eyewitness contact details if available, to the appointment.
D - Patients with treatment-resistant epilepsy should have the opportunity to receive shared care to enable accurate classification and tailored management of their seizures.
D - Women of childbearing potential who are taking antiepileptic drugs should receive information about contraception, conception and pregnancy at their regular structured review in primary care and should have the opportunity to be referred to secondary care to have their diagnosis and treatment reviewed by specialist services before conception.
D - Patients referred following a suspected first seizure or new epilepsy should be advised not to drive until they have seen an epilepsy specialist.
D - Patients with epilepsy who hold a driving license and who continue to have seizures should be made aware of current Driver and Vehicle Licensing Agency (DVLA) regulations.
Role of the Epilepsy Specialist Nurse
D - Each epilepsy team should include epilepsy specialist nurses.
Levels of Evidence
1++: High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias
1+: Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias
1-: Meta-analyses, systematic reviews, or RCTs with a high risk of bias
2++: High-quality systematic reviews of case-control or cohort studies
High-quality case-control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
2+: Well-conducted case-control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal
2-: Case-control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3: Non-analytic studies (e.g., case reports, case series)
4: Expert opinion
Grades of Recommendation
Note: The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation.
A: At least one meta-analysis, systematic review, or RCT rated as 1++ and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results
B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D: Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+