Any amendments to the guideline will be noted on the Scottish Intercollegiate Guidelines Network (SIGN) Web site.

• December 12, 2007, Carbamazepine: The U.S. Food and Drug Administration (FDA) has provided recommendations for screening that should be performed on specific patient populations before starting treatment with carbamazepine.
• September 17, 2007, Haloperidol (Haldol): Johnson and Johnson and the U.S. Food and Drug Administration (FDA) informed healthcare professionals that the WARNINGS section of the prescribing information for haloperidol has been revised to include a new Cardiovascular subsection.

Note from the National Guideline Clearinghouse (NGC): In June 2004 the Scottish Intercollegiate Guidelines Network (SIGN) released an update to this guideline, available on the SIGN Web site . The only change to the following recommendations is denoted below in bold italics.

Note from SIGN and NGC: In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice 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.

Diagnosis

Who should make the diagnosis of epilepsy?

C: The diagnosis of epilepsy should be made by a neurologist or other epilepsy specialist.

Classification

C: The seizure type(s) and epilepsy syndrome should be identified.

C: The distinction should be made between a focal epilepsy and an idiopathic 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: Electroencephalography (EEG) is not routinely indicated and should not be performed to "exclude" a diagnosis of epilepsy.

C: EEG can be used to support the diagnosis in patients in whom the clinical history indicates a significant probability of an epileptic seizure or 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.

C: Video EEG and other specialist investigations should be available for patients who present diagnostic difficulties.

Brain Imaging

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 an idiopathic generalised epilepsy and if there is rapid and complete response to the first line antiepileptic drug.

D: Computed tomography (CT) has a role in the urgent assessment of seizures, or when magnetic resonance imaging is contraindicated.

Treatment

When and by Whom Should Antiepileptic Drug (AED) Treatment be Commenced?

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 congenital neurological deficit
• D: The patient considers the risk of recurrence unacceptable

Antiepileptic Drug Monotherapy

A: Carbamazepine, sodium valproate, lamotrigine and oxcarbazepine can all be regarded as first-line treatments for partial and secondary generalised seizures.

A: Sodium valproate and lamotrigine are drugs of choice for primary generalised seizures and should also be prescribed if there is any doubt about the seizure types and/or syndrome classification.

A: The side effect and interaction profiles should direct the choice of drug for the individual patient.

Note: Formulations of AEDs are not interchangeable and generic substitution should not be employed. All antiepileptic drugs licensed for monotherapy have similar efficacy in newly-diagnosed epilepsy.

Management of Drug-resistant Epilepsy

C: Failure to respond to appropriate AEDs should prompt a review of the diagnosis of epilepsy and adherence to medication.

A: Combination therapy should be considered when treatment with two first line AEDs has failed or when the first well-tolerated drug substantially improves seizure control but fails to produce seizure-freedom at maximal dosage.

B: The choice of drugs in combination should be matched to the patient's seizure type(s) and should be limited to two or at most three AEDs.

Antiepileptic Drug Blood Levels

D: Routine monitoring of AED concentrations is not indicated. Measurement can sometimes be useful in the following circumstances:

• Adjustment of phenytoin dose
• Assessment of adherence and toxicity

D: Assay of lamotrigine, vigabatrin, gabapentin, topiramate, tiagabine, oxcarbazepine and levetiracetam concentrations should not be undertaken routinely.

Management of Provoked Seizures

B: Short term benzodiazepine treatment may be given to reduce the risk of seizures in the context of acute alcohol withdrawal and delirium tremens.

B: Following an acute brain insult or neurosurgery, prophylactic AED treatment is not indicated.

C: Following an acute brain insult, AEDs used to treat the provoked seizures should be withdrawn (unless unprovoked seizures occur later).

D: AED treatment is not indicated for concussive convulsions.

Antiepileptic Drug Side Effects

C: Patients should be warned of potential side 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: Patients taking AEDs should receive dietary and other lifestyle advice to minimise the risk of osteoporosis.

C: Liver function and full blood count should not be monitored routinely.

Antiepileptic Drug Withdrawal

A: Prognostic index indicators can be used to give an estimate of the risks of seizure recurrence following AED withdrawal (refer to tables 2 and 3 in the original guideline document).

Psychological Treatment of Epilepsy

B: Psychological treatments are not an alternative to pharmacological treatments, but their use can be considered in patients with poorly controlled seizures.

Surgical Referral

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.

Management of Status Epilepticus

Immediate measures

D: In the community or in hospital, patients with generalised tonic-clonic status epilepticus should be managed immediately as follows (with local protocols being in place):

• Secure airway
• Give oxygen
• Assess cardiac and respiratory function
• Secure intravenous (IV) access in large veins

A: Give lorazepam 4 mg IV or diazepam 10 mg IV if lorazepam is unavailable. This can be repeated in hospital after 10 minutes if there is no response. If there is a delay in gaining IV access in the community: give diazepam 10-20 mg rectally (rectal solution or IV solution).

D: In hospital:

• Collect blood for full blood count, urea and electrolyte, liver function tests, calcium, glucose, clotting, AED levels and storage for later analyses
• Measure blood gases to assess extent of acidosis
• Establish aetiology. Give 50 ml 50% glucose IV if there is any suggestion of hypoglycaemia and IV thiamine (given as Pabrinex two pairs of ampoules) if there is any suggestion of alcohol abuse or impaired nutritional status

Within 30 minutes

D: For sustained control in patients with established epilepsy, within 30 minutes:

• Give usual AED treatment orally or by nasogastric tube (or IV if necessary for phenytoin, sodium valproate and phenobarbital).

B: For sustained control in other patients or if seizures continue, within 30 minutes:

• Give fosphenytoin in a dose of 18 mg/kg phenytoin equivalent (PE) IV, up to 150 mg/min with electrocardiography (ECG) monitoring; or phenytoin 18 mg/kg IV, 50 mg/min with ECG monitoring or phenobarbital 15 mg/kg IV, 100 mg/min. Rates of infusion may need to be reduced if hypotension or arrhythmia occur or in elderly or renal/ hepatic impairment.

Longer than 30 minutes

D: If status persists, then within 60 minutes:

• Admit to intensive treatment unit (ITU) and administer general anaesthesia
• Monitor using EEG to assess seizure control
• Refer for specialist advice

Non-convulsive status epilepticus

D: Patients with non-convulsive status epilepticus should be managed as follows:

• Maintain or reinstate usual oral AED treatment
• Consider lorazepam 4 mg IV or diazepam 10 mg IV
• Refer for specialist advice

Patients with recurrent prolonged or serial seizures in the community

A: Patients with recurrent prolonged or serial seizures in the community should be initially managed by carers who should give diazepam 10-20 mg rectally according to an agreed protocol (protocols must include advice on when to transfer to hospital).

Management of People with Learning Disability and Epilepsy

D: In the management of people with learning disability and epilepsy:

• Adequate time should be allowed for the consultation
• The carer should know the patient and bring relevant information on seizure type, frequency, possible side effects of medication, general health and behaviour to the consultation
• Information in an accessible form should be available to clients and carers
• There should be a multidisciplinary approach to treatment, delivered by professionals with an expertise in epilepsy, to improve quality of life. Community learning disability nurses have an important role in liaising between the specialist services and clients and carers

Advice on Rectal Diazepam or Equivalent Emergency Medication

D: All carers of patients with learning disability and epilepsy who may require rectal diazepam, should receive recognised training in its administration. Retraining should take place every two years.

D: A care plan should be drawn up in consultation with the general practitioner (GP) and/or specialist service, used by everyone working with the individual client, and reviewed at regular intervals.

D: Adequate support and instruction should be given to families.

Contraception, Pregnancy and Hormone Replacement Therapy (HRT)

Contraception

Combined oral contraceptive (COC)

D: When the combined oral contraceptive is given with an enzyme-inducing AED, one containing a minimum of 50 micrograms of oestrogen should be used; women should be warned that its efficacy is reduced and barrier methods of contraception should also be used if maximal contraceptive effect is required.

D: If breakthrough bleeding occurs with 50 micrograms of oestrogen the dose should be increased and "tricycling" of the combined oral contraceptive should be considered.

Progesterone-only contraception

D: The progesterone-only oral contraceptive is not recommended for women taking enzyme-inducing AEDs.

D: Depot injections of progesterone may be used with enzyme-inducing AEDs but should be given every 10 weeks.

D: Progesterone implants are not suitable for women taking enzyme-inducing AEDs.

Emergency contraception

D: The dose of levonorgestrel for emergency contraception should be increased to 1.5 mg and 750 micrograms 12 hours apart in women taking enzyme-inducing AEDs.

Preconceptual Counseling

Risks to the fetus from maternal epilepsy

D: Women should be made aware of the risks of uncontrolled seizures both to themselves and to the fetus.

Risks to the fetus from antiepileptic drugs

C: If AEDs are to be used in pregnancy the relative risks of seizures and fetal malformation should be discussed with the woman.

C: Whenever possible, a woman should conceive on the lowest effective dose of one AED appropriate for her epilepsy syndrome. If she has good seizure control and presents already pregnant, there is probably little to be gained by altering her AEDs.

D: Any woman who has given birth to a child with a malformation while taking AEDs should be offered review by an epilepsy specialist before becoming pregnant again.

Folic acid

D: All women with epilepsy should be prescribed a daily dose of 5 mg folic acid from preconception until the end of the first trimester.

Vitamin K ₁

C: All infants born to mothers taking AEDs should be given vitamin K₁ 1 mg intramuscularly at birth.

D: If there are additional risk factors for haemorrhagic disease of the newborn (e.g., maternal liver disease, anticipated premature delivery) oral vitamin K₁ (phytomenadione 10 mg daily) should also be given in the last month of pregnancy.

Pregnancy

D: If preterm labour is threatened in women taking enzyme-inducing AEDs, 48 mg betamethasone (double the normal dose) should be given over 48 hours.

AED doses and blood level monitoring during pregnancy

D: Dose of AEDs should not be increased routinely in pregnancy but should only be adjusted on clinical grounds.

Labour

D: The usual oral AED medication should be continued during labour and postnatally. In women unable to tolerate oral medication, AEDs can be given by other routes.

Seizures in labour

D: Seizures in labour should be terminated as soon as possible using intravenous lorazepam or diazepam. If seizures persist, manage as for status epilepticus.

Risks of inheriting epilepsy

Febrile convulsions

D: A comprehensive family history of epilepsy should be taken and expert advice on the genetics of epilepsy should be available as required.

Hormone replacement therapy (HRT)

D: Women should be aware that their seizure pattern may change at the time of the menopause.

D: Hormone replacement therapy should be prescribed for the same indications as in women who do not have epilepsy.

Models of Care

Models of Primary and Shared Care for Epilepsy

D: A structured management system for epilepsy should be established in primary care. As with other chronic diseases, an annual review is desirable.

D: The annual review would be facilitated and enhanced by the deployment of 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 to a specialist centre
• Monitor seizures, aiming to improve control by adjustment of medication or re-referral to hospital services
• Minimise side 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 quality of life for patients with epilepsy
• Address specific women's issues and needs of patients with learning disabilities

Information for Discussion with Patients and Carers

Advice and Information on Epilepsy

D: A checklist should be used to help healthcare professionals to give patients and carers the information they need in an appropriate format (refer to the original guideline document for an example information checklist).

Outcome measures

Seizure Frequency

D: Assessments should always include seizure frequency and date of last seizure.

Definitions:

Grades of Recommendations

A: At least one meta-analysis, systematic review of randomised controlled trials (RCTs), or randomised controlled trial 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 rate as 2++

D: Evidence level 3 or 4; or

Extrapolated evidence from studies rated as 2+

Good Practice Points: Recommended best practice based on the clinical experience of the guideline development group.

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 of RCTs, 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

Any amendments to the guideline will be noted on the Scottish Intercollegiate Guidelines Network (SIGN) Web site.

Electronic copies: Available in Portable Document Format (PDF) from the Scottish Intercollegiate Guidelines Network (SIGN) Web site.

Electronic copies of Addendum: Available from the SIGN Web site.

• Quick reference guide: Diagnosis and management of epilepsy in adults. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2003 Apr. 2 p. Available in Portable Document Format (PDF) from the Scottish Intercollegiate Guidelines Network (SIGN) Web site.
• SIGN 50: a guideline developers' handbook. Edinburgh ( UK): Scottish Intercollegiate Guidelines Network. (SIGN publication; no. 50). Available from the SIGN Web site.
• Appraising the quality of clinical guidelines. The SIGN guide to the AGREE (Appraisal of Guidelines Research and Evaluation) guideline appraisal instrument. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network, 2001. Available from the SIGN Web site.
• A background paper on the legal implications of guidelines. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network.

Electronic copies: Available from the Scottish Intercollegiate Guidelines Network (SIGN) Web site.

Please note: This patient information is intended to provide health professionals with information to share with their patients to help them better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether or not it accurately reflects the original guideline's content.

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