Management of epilepsy

NICE CG137- Epilepsies: diagnosis and management (Updated February 2016) contains guidance on the diagnosis and management of the epilepsies in adults, children and young people in primary and secondary care. This section summarises some of this guidance and provides other useful information on epilepsy.

All patients having a first seizure should be seen as soon as possible by a specialist in the management of the epilepsies to ensure precise and early diagnosis and initiation of therapy as appropriate to their needs. Patients will be seen within two weeks of referral. Treatment is not generally initiated after a single fit.

Essential information on how to recognise a seizure, first aid, and the importance of reporting further attacks should be provided to the patient who has experienced a possible first seizure, and their family/carer/parent as appropriate.

Women of child-bearing potential require special consideration (see Women and girls with epilepsy).

Drug treatment

See section 4.8 Antiepileptic drugs

NICE CG137 recommends drug treatment be individualised according to seizure type, epilepsy syndrome, co-medication and co-morbidity, patient's lifestyle, and the preferences of the person, their family and/or carers as appropriate, see full guidance for further details. In clinical practice the type of seizure can be used to guide treatment choice.

Side effect and interaction profiles should direct the choice of drug for the individual patient.

The MHRA issued a strengthened warning that valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. See MHRA Drug Safety Update (February 2016): Valproate and risk of abnormal pregnancy outcomes: new communication materials.

Despite communications to prescribers in January 2015 and February 2016 on the magnitude of this risk and the actions to take, there is evidence that women are still not aware of the risk. Patient Safety Alerts have now been issued asking all organisations to undertake systematic identification of women and girls taking valproate. See MHRA Drug Safety Update (April 2017): Valproate and developmental disorders: new alert asking for patient review and further consideration of risk minimisation measures.

Different antiepileptic drugs (AEDs) vary considerably in their characteristics, which influences the risk of whether switching between different manufacturers' products of a particular drug may cause adverse effects or loss of seizure control. See MHRA Drug Safety Update - Antiepileptic drugs: new advice on switching between different manufacturers' products for a particular drug (November 2013). See 4.8.1 Control of the epilepsies.

Starting treatment

  • The decision to start anti-epileptic drug (AED) treatment should be made after full discussion of the risks and benefits and should be made between the person with epilepsy (and family/carers as appropriate) and an epilepsy specialist.
  • AED therapy should only be started once the diagnosis is confirmed, except in exceptional circumstances.
  • AED therapy is generally recommended after a second epileptic seizure. AED therapy can be considered after a first unprovoked seizure in certain circumstances (neurological deficit, EEG shows unequivocal epileptic activity, the risk of a further seizure is considered unacceptable by the individual/carer, brain imaging shows structural abnormality).
  • The risk of sudden death in epilepsy (SUDEP) can be minimised by optimising seizure control and being aware of the potential consequences of nocturnal seizures.
  • AEDs have been associated with a small increased risk of suicidal thoughts and behaviour; this can occur as early as 1 week after starting treatment. Patients should be advised to seek medical advice if they develop mood changes or suicidal thoughts. Citalopram is an appropriate option for patients with epilepsy requiring an antidepressant. See 4.3.3 Selective serotonin re-uptake inhibitors.

An epilepsy specialist should:

  • recommend initiation of appropriate treatment
  • plan continuation of treatment
  • manage or provide guidance for withdrawal of treatment

Monotherapy

  • Monotherapy with a single AED is preferred.
  • If treatment with the initial AED is unsuccessful give a different AED (either an alternative first-line or a second-line drug). Increase the second AED to an adequate or maximum tolerated dose
    • if the second AED is helpful, slowly taper off the first AED,
    • if the second AED is unhelpful, taper either the first or second drug, depending on reasons for lack of success (relative efficacy, side effects, tolerability) before starting another drug
  • Caution is required when switching AEDs.

Combination therapy

  • Review diagnosis of epilepsy and adherence to medication.
  • Consider combination therapy when:
    • treatment with two first line AEDs has failed
    • the first well-tolerated drug substantially improves seizure control, but fails to produce seizure freedom at maximal dosage
  • The choice of drugs in combination should be matched to the patient's epileptic syndrome or seizure type(s) and should be limited to two or at most three AEDs.
  • If the second drug is unhelpful, taper either the first or second drug (depending on relative efficacy, side effects and tolerability) before starting another drug.
  • If trials of combination therapy do not bring about worthwhile benefits, revert to the regimen (monotherapy or combination therapy) that has provided the best balance between tolerability and reducing seizure frequency.

1st and 2nd line treatment options

The following guidance summarises 1st line and 2nd line treatment options outlined in NICE CG137 based on seizure type. Consult NICE guidance for 3rd line and adjunct treatments.

See section 4.8 Antiepileptic drugs

Focal

  • First line: Carbamazepine MR or Lamotrigine
  • Second line: Levetiracetam or Oxcarbazepine or Sodium valproate

Primary generalised tonic-clonic

  • First line: Sodium valproate
  • Second line: Lamotrigine

Absence

  • First line: Sodium valproate or Ethosuximide
  • Second line: Lamotrigine

Myoclonic

  • First line: Sodium valproate
  • Second line: Levetiracetam or Topiramate

Tonic or atonic

  • First line: Sodium valproate

Prolonged or repeated seizures in the community

Patients experiencing convulsive seizures which last longer than 5 minutes or three or more seizures in an hour require prompt care and treatment.

Action:

  • Remain with the person.
  • Protect head during the seizure.
  • When seizure stops, check airways, breathing etc.
  • If prescribed, treat with either buccal midazolam or rectal diazepam.
  • Call emergency services if:
    • the seizure is continuing 5 minutes after the emergency medication has been administered
    • the person has a history of frequent episodes of serial seizures or has convulsive status epilepticus or this is the first episode requiring emergency treatment
    • there are concerns of difficulties monitoring the person's airway, breathing, circulation or other vital signs.

Treatment options see section 4.8 Antiepileptic drugs

  • Midazolam buccal liquid
  • Diazepam rectal tubes

Continuing and withdrawing treatment

NICE guidance on continuing treatment

Continuing AED therapy should be planned by a specialist. If the management is straightforward, then continuation may be in primary care.

Regular blood level monitoring should only be carried out if clinically indicated, e.g. detection of non-adherence, suspected toxicity, adjustment of phenytoin dose, specific clinical conditions such as organ failure.

Some specific routine blood tests should be conducted; clotting studies before surgery in patients taking valproate, FBC, U&E, LFT, vitamin D and bone metabolism in patients taking enzyme inducing drugs and valproate should be conducted every 2-5 years. Asymptomatic minor abnormalities are not necessarily an indication to change medication.

Available data suggest that long-term use of carbamazepine, phenytoin, primidone and sodium valproate is associated with decreased bone mineral density that may lead to osteopenia, osteoporosis, and increased fractures in at-risk patients. Vitamin D supplementation should be considered for at-risk patients who are taking the above medicines and phenobarbital long-term. Patients taking AEDs should receive dietary and other lifestyle advice to minimise the risk of osteoporosis.

Withdrawing anti-epileptic medication

Appendix H of the full NICE CG137 provides tables for the prognosis of remission of seizures

The decision to withdraw medication should be taken by the individual/carer and the specialist after full discussion of the risks and benefits of withdrawal. Withdrawal should be managed by, or be under the guidance of, the specialist.

NICE guidance on withdrawing AEDs:

  • Withdraw one AED at a time, over at least 2 to 3 months
  • Withdraw benzodiazepines and barbiturates over ≥ 6 months to prevent withdrawal symptoms and/or seizure recurrence
  • Advise patients that if seizures recur during withdrawal to reverse the last dose reduction and seek medical advice

Women and girls with epilepsy

In order to enable informed decisions and choice, and to reduce misunderstandings, women and girls with epilepsy and their partners, as appropriate, must be given accurate information and counselling about contraception, conception, pregnancy, caring for children and breastfeeding, and menopause.

Discuss with women and girls of childbearing potential, and their parents and/or carers if appropriate, the risk of AEDs causing malformations and possible neurodevelopmental impairments in an unborn child. Assess the risks and benefits of treatment with individual drugs.

MHRA Drug Safety Update (February 2016): Valproate and risk of abnormal pregnancy outcomes: new communication materials to be used to support discussion of the risks with females of child bearing potential and girls who take valproate.

MHRA Drug Safety Update (April 2017): Valproate and developmental disorders: new alert asking for patient review and further consideration of risk minimisation measures.

  1. ensure women and girls taking valproate medicines understand the 30–40% risk of neurodevelopmental disorders and 10% risk of birth defects, and are using effective contraception
  2. valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated; migraine is not a licensed indication
  3. valproate use in women and girls of childbearing potential must be initiated and supervised by a specialist experienced in managing epilepsy or bipolar disorder
  4. carefully balance the benefits of valproate treatment against the risks when prescribing valproate for the first time, at routine treatment reviews, when a female child reaches puberty and when a woman plans a pregnancy or becomes pregnant
  5. you must ensure that all female patients are informed of and understand:
    1. risks associated with valproate during pregnancy
    2. need to use effective contraception
    3. need for regular review of treatment
    4. the need to rapidly consult if she is planning a pregnancy or becomes pregnant
  6. Patient Safety Alert to further highlight risks to the unborn child and support the safety of girls and women taking valproate

The Medicines and Healthcare Products Regulatory Agency's (MHRA) Toolkit on the risks of valproate medicines in female patients, provides resources to ensure female patients are better informed about the risks of taking valproate medicines during pregnancy.

Contraception

AEDs can interact with hormonal contraceptives; see Contraception Guidance for more information

Epilepsy itself is a condition for which there are no restrictions on the use of contraceptive methods, but restrictions may apply if certain antiepileptic drugs (AEDs) are used.

If a patient is using oral contraception, an AED that does not induce hepatic enzymes is preferable.

Combined hormonal contraceptive (CHC)

When a CHC is given with an enzyme inducing AED the efficiency of the contraceptive is reduced. Other non-hormonal methods of contraception should be used.

AEDs which induce hepatic enzymes

  • Carbamazepine
  • Eslicarbazepine
  • Oxcarbazepine
  • Phenobarbitone
  • Phenytoin
  • Primidone
  • Topiramate

Progestogen only contraception (POP)

POP is not recommended for women taking enzyme inducing AEDs.

Progestogen implants are not suitable for women taking enzyme inducing AEDs.

Women started on an enzyme-inducing AED should be advised to use a reliable contraceptive method unaffected by enzyme inducers (e.g. progestogen-only injectable, Cu-IUD, levonorgestrel-releasing intrauterine system or non-hormonal methods). For advice concerning CHCs and depot progestogens, it is advisable to contact The Centre. Telephone: 01392 284982 or 01392 284983. See also CHC Drug interactions.

Pregnancy

All AEDs have potential harmful effects on the unborn child, as does epilepsy. Women and girls with epilepsy need accurate information during pregnancy, and the possibility of status epilepticus and SUDEP should be discussed with all women and girls who plan to stop AED therapy

Pre-conception counselling by a specialist is recommended. To reduce the risk of neural tube defects adequate folate supplements are advised for women before and during pregnancy; to prevent recurrence of neural tube defects, women should receive folic acid 5mg daily. This dose may also be appropriate for women receiving antiepileptic drugs. See section 9.1 Anaemias and some other blood disorders. Those who wish to become pregnant should be referred to an appropriate specialist for advice. Women who become pregnant should be counselled and offered antenatal screening (alpha-fetoprotein measurement and a second trimester ultrasound scan).

Routine injection of vitamin K at birth minimises the risk of neonatal haemorrhage associated with antiepileptics.

The concentration of antiepileptic drugs in the blood can change during pregnancy, particularly in the later stages. The dose of antiepileptics should be monitored carefully during pregnancy and after birth, and adjustments made on a clinical basis.

The care of pregnant women should be shared between the obstetrician and epilepsy specialist. The reporting of the pregnancy to the UK Epilepsy and Pregnancy Register is encouraged (Tel: 0800 389 1248)

Full NICE guidance contains more details of these issues.

Breastfeeding

Prescribers should consult individual drug advice in the SPC and the BNF (available at https://www.medicinescomplete.com/about/) when prescribing AEDs for women and girls who are breastfeeding. The decision regarding AED therapy and breastfeeding should be made between the woman or girl and the prescriber, and be based on the risks and benefits of breastfeeding against the potential risks of the drug affecting the child.

Driving and epilepsy

Patients with epilepsy may drive a motor vehicle (but not a large goods or passenger carrying vehicle) provided that they have been seizure-free for one year or, if subject to attacks only while asleep, have established a 3-year period of asleep attacks without awake attacks. Those affected by drowsiness should not drive or operate machinery.

Anti-epileptics can make patients drowsy or sleepy and cause blurred vision or double vision when starting treatment. Care must be taken if driving or when operating any type of machinery. It is essential that epilepsy as well as sudden disabling attacks of loss, or partial loss, of consciousness is reported to the Driver and Vehicle Authority (DVLA). The DVLA will then make a medical assessment of the illness, asking the patient's doctor(s) where necessary.

For more information, see https://www.gov.uk/epilepsy-and-driving

It is also recommended that the patient informs their insurance company if they are taking these drugs. If they do not, and have an accident, it could affect any insurance cover.

 

Home > Formulary > Chapters > 4. Central Nervous System > Management of epilepsy

 

  • First line
  • Second line
  • Specialist
  • Hospital