Guia NICE epilepsia

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The epilepsies

Implementing NICE guidance

January 2012

NICE clinical guideline 137

Updated guidance

This guideline updates and replaces ‘The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care’ (NICE clinical guideline 20, 2004).

This guidance also updates and replaces NICE technology appraisals 76 and 79.

New recommendations for pharmacological treatment have been added.

What this presentation covers

Background

Scope

Guideline recommendations

Costs and savings

Discussion

NICE Pathway, NHS Evidence andNational Prescribing Centre

Find out more

Background

• Epilepsy: common neurological disorder characterised by recurring seizures.

• The majority of people with active epilepsy can satisfactorily control recurrent seizures.

• Optimal management improves health outcomes and minimises detrimental impacts on health.

• Newer anti-epileptic drugs are currently being prescribed, so it is important that clinical and cost effectiveness are identified.

Epidemiology

• The epilepsies comprise the most common serious neurological disorders.

• Estimated to affect between 362,000 and 415,000 people in England.

• Estimated incidence: 50 per 100,000.

• Estimated prevalence of active epilepsy in the UK: 5−10 cases per 1000.

Scope

This guideline provides recommendations for the treatment of children, young people adults and older people with a diagnosis of any type of epilepsy. Treatments for neonates are not covered by this guideline.

It covers all seizure types and epilepsy syndromes.

Recommendations are relevant to healthcare professionals who have direct contact with, and make decisions concerning, the care of people with epilepsy.

Healthcare professionals should:

• adopt a consulting style that enables people with epilepsy to participate as partners in decisions about their healthcare

• take into account their race, culture and any specific needs.

Decision making

[2004]

• People with epilepsy should have access to information about all aspects of their condition. This information should be provided in suitable formats.

• Adequate time should be set aside at consultation to provide information, and checklists should be used to ensure all information is discussed.

• In high-risk individuals, the possibility of having seizures should be discussed, and information about epilepsy should be provided before seizures occur.

Information

[2004]

• Tailored information and discussion on a person’s relative risk of SUDEP should be provided.

• The risk of SUDEP can be minimised by optimising seizure control and being aware of potential consequences of nocturnal seizures.

• Where families/carers have been affected by SUDEP, healthcare professionals should contact them to offer their condolences and referral to bereavement counselling.

Sudden unexpected death in epilepsy (SUDEP)

[2004]

• People presenting at A&E should be screened initially with onward referral to a specialist when an epileptic seizure is suspected or if there is diagnostic doubt.

• Protocols should be in place that ensure proper assessment in the emergency setting.

• All people should be seen as soon as possible and within 2 weeks, by a specialist in the management of the epilepsies.

Following a first seizure

[2004]

• Diagnosis should be established by a specialist medical practitioner and the opportunity to discuss this diagnosis should be given.

• The decision as to whether an epileptic seizure has occurred should be based on a description of the attack and different symptoms.

• If the diagnosis cannot be clearly established, further investigations and referral to a tertiary specialist should be considered.

Diagnosis

[2004]

• Those requiring an EEG should have the test performed soon (within 4 weeks) after requested, and it should only be performed to support a diagnosis of epilepsy.

• An EEG should not be performed in the case of probable syncope or used to exclude a diagnosis of epilepsy. It should also not be used in isolation to make a diagnosis.

• An EEG may be used to help determine seizure type and epilepsy syndrome.

Investigations: electroencephalogram (EEG): 1

[2004]

• In those presenting with a first unprovoked seizure, an EEG can be used to assess risk of seizure recurrence.

• Repeated standard EEGs may be helpful when the diagnosis of epilepsy or the syndrome is unclear. These should not be used in preference to sleep or sleep-deprived EEGs.

• Photic stimulation and hyperventilation should remain part of standard EEG assessment.

Investigations: electroencephalogram (EEG): 2

[2004]

• Neuroimaging should be used to identify structural abnormalities.

• MRI should be the imaging of choice and is important in those who develop epilepsy before the age of 2 or in adulthood, those who have a suggestion of focal onset and those in whom seizures continue.

• CT should be used to identify underlying gross pathology if MRI is not available or if sedation for MRI is required.

Investigations: neuroimaging

[2004]

• Measurement of serum prolactin is not recommended.

• Appropriate blood tests should be considered.

• A 12-lead ECG should be performed in adults with suspected epilepsy and children in cases of diagnostic uncertainty.

• In cases of diagnostic uncertainty a referral to a cardiologist should be considered.

Other tests

[2004]

This should be considered when it is important to evaluate learning disabilities and cognitive dysfunction.

Referral for assessment is indicated:•when those with epilepsy are having educational or occupational difficulties•when an MRI had identified abnormalities•when a person complains of memory or other cognitive deficits or cognitive decline.

Neuropsychological assessment

[2004]

• People should have an accessible point of contact with specialist services.

• All those with epilepsy should have a comprehensive, agreed care plan.

• Epilepsy specialist nurses should be an integral part of the network of care.

• Healthcare professionals have a responsibility to educate others to reduce stigma.

Management

[2004]

• The anti-epileptic drug (AED) treatment strategy should be individualised.

• The diagnosis of epilepsy should be evaluated if events continue despite an optimal dose of a first-line AED.

Pharmacological treatment: 1

[2004]


• Consistent supply of a particular manufacturer's AED preparation is recommended as different preparations of some AEDs may vary in bioavailability or pharmacokinetic profiles and care needs to be taken to avoid reduced effect or excessive side effects.

• People with epilepsy should be treated with a single AED wherever possible.

[2004]

[2012]

• If an AED has failed, a second drug should be started and built up to adequate dose, then the first drug should be tapered off slowly.

• Combination therapy should only be considered when attempts at monotherapy have not resulted in seizure freedom.


[2004]

• If using carbamazepine, offer controlled-release carbamazepine preparations.

• When prescribing sodium valproate to women and girls of present and future childbearing potential, discuss the possible risks of malformation and neurodevelopmental impairments.


[2012]

• AED therapy should only start on the recommendation of a specialist and once the diagnosis of epilepsy is confirmed.

• The decision to start therapy should be taken between the person and specialist after a full discussion of the risks and benefits to treatment.

• When possible choose which AED to offer based on the epilepsy syndrome. If this is not clear, base the decision on the presenting seizure.

Initiation of pharmacological treatment

[2004]

[2012]

Click on the boxes to view the treatment recommendations for each syndrome type.

Epilepsy syndrome type

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

Treatment of childhood absence epilepsy, juvenile absence epilepsy or other absence epilepsy syndromes

Refractory convulsive status epilepticus

Dravet syndrome

Juvenile myoclonic epilepsy

Lennox–Gastaut syndrome

Other epilepsy syndromes

More syndrome types

Click on the boxes to view the treatment recommendations for each syndrome type.

Epilepsy syndrome type: 2

Infantile spasms

Treatment of epilepsy with generalised tonic-clonic (GTC) seizures only

Prolonged or repeated seizures and convulsive status epilepticus in the community

Convulsive status epilepticus in hospital

Idiopathic generalised epilepsy

Back to previous list

To go to recommendations for seizure types

Click on the boxes to view the treatment recommendations for each seizure/syndrome type.

Seizure type

Focal seizures GTC seizures

Absence seizure Myoclonic seizure

Tonic or atonic seizures

Click here to continue to non-pharmacological recommendations

Back to epilepsy syndromes

• Offer carbamazepine or lamotrigine.

• Offer levetiracetam, oxcarbazepine or sodium valproate (provided the acquisition cost of levetiracetam falls to at least 50% of June 2011- see presenter notes for more information) if carbamazepine and lamotrigine are unsuitable or not tolerated. If the first-line AED is ineffective, offer an alternative from these five AEDs.

• Consider adjunctive treatment if second AED ineffective.

First-line treatment of focal seizures

[2012]

For adjunctive treatment click here To go back to seizure/syndrome type slide click here

• Offer carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate or topiramate.

• 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 specialist are eslicarbazepine acetate, lacosamide, phenobarbital, phenytoin, pregabalin, tiagabine, vigabatrin and zonisamide.

Adjunctive treatment of refractory focal seizures

[2012] To go back to seizure/syndrome type slide click here

• Offer sodium valproate. Be aware of teratogenic risks.

• Offer lamotrigine if sodium valproate is unsuitable. Be aware that this AED may exacerbate myoclonic seizures.

• Consider carbamazepine and oxcarbazepine. Be aware that these AEDs may exacerbate myoclonic or absence seizures.

First-line treatment of newly diagnosed GTC seizures

[2012]

To go back to seizure/syndrome type slide click here

For adjunctive treatment click here

• Offer clobazam, lamotrigine, levetiracetam, sodium valproate or topiramate.

• If there are absence or myoclonic seizures, or if juvenile myoclonic epilepsy (JME) is suspected, do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Adjunctive treatment of GTC seizures

[2012]To go back to seizure/syndrome type slide click here

• Offer ethosuximide or sodium valproate. 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.

First-line treatment of absence seizures

[2012]



• Consider a combination of two of these three AEDs as adjunctive treatment: ethosuximide, lamotrigine or sodium valproate.

• If 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.

Adjunctive treatment of absence seizures


• Offer sodium valproate unless it is unsuitable.

• Consider levetiracetam or topiramate if sodium valproate is unsuitable or not tolerated. Be aware that topiramate has a less favourable side-effect profile than levetiracetam and sodium valproate.

First-line treatment of myoclonic seizures

[2012]



• Offer levetiracetam, sodium valproate or topiramate.

• If ineffective discuss with, or refer to, a tertiary epilepsy specialist and consider clobazam, clonazepam, piracetam or zonisamide.


Adjunctive treatment of myoclonic seizures

[2012]To go back to seizure/syndrome type slide click here

• Offer sodium valproate. Be aware of teratogenic risks.

First-line treatment of tonic or atonic seizures

[2012]



• If first-line treatment with sodium valproate is ineffective or not tolerated, offer lamotrigine.

• 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.

Adjunctive treatment of tonic or atonic seizures


• Discuss with, or refer to, a tertiary paediatric epilepsy specialist.

• Offer a steroid (prednisolone or tetracosactide) or vigabatrin to infants with infantile spasms that are not due to tuberous sclerosis.

• Offer vigabatrin to infants with infantile spasms due to tuberous sclerosis. If vigabatrin is ineffective, offer a steroid.

Treatment of infantile spasms



• Consider sodium valproate or topiramate.

First-line treatment of Dravet syndrome

[2012]



• Discuss with a tertiary epilepsy specialist and consider clobazam or stiripentol.

• Do not offer carbamazepine, gabapentin, lamotrigine, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin.

Adjunctive treatment of Dravet syndrome

[2012]



• Offer sodium valproate.

First-line treatment of Lennox–Gastaut syndrome

[2012]



• Offer lamotrigine.

• Discuss with a tertiary epilepsy specialist if lamotrigine ineffective or not tolerated. Other AEDs which may be considered: rufinamide and topiramate.

• Do not offer carbamazepine, gabapentin, oxcarbazepine, pregabalin, tiagabine or vigabatrin.

• Only offer felbamate in centres providing tertiary epilepsy specialist care and when all of the above AEDs have proved ineffective.

Adjunctive treatment of Lennox–Gastaut syndrome


• Discuss whether AED treatment is indicated.

• Offer carbamazepine or lamotrigine.

• Offer levetiracetam, oxcarbazepine or sodium valproate (provided the acquisition cost of levetiracetam falls- see presenter notes for more information) if carbamazepine and lamotrigine are unsuitable or not tolerated. If the first AED tried is ineffective, offer an alternative from these five AEDs.

First-line treatment of benign epilepsy with centrotemporal spikes,

Panayiotopoulos syndrome or late-onset childhood occipital epilepsy (Gastaut type)

[2012] For adjunctive treatment click here


• Offer carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate or topiramate.

• If ineffective or not tolerated discuss with, or refer to, a tertiary epilepsy specialist. Other AEDs that may be considered are eslicarbazepine acetate, lacosamide, phenobarbital, phenytoin, pregabalin, tiagabine, vigabatrin and zonisamide.

Adjunctive treatment of benign epilepsy with centrotemporal spikes,

Panayiotopoulos syndrome or late-onset childhood occipital epilepsy (Gastaut type)


• Offer sodium valproate.

• Offer lamotrigine if sodium valproate is unsuitable or not tolerated.

• Consider topiramate but be aware that it has a less favourable side-effect profile than sodium valproate and lamotrigine.

First-line treatment of idiopathic generalised epilepsy

[2012]

For adjunctive treatment click here To go back to seizure/syndrome type slide click here

• Offer lamotrigine, levetiracetam, sodium valproate or topiramate.

• If ineffective or not tolerated discuss with, or refer to, a tertiary epilepsy specialist and consider clobazam, clonazepam or zonisamide.


Adjunctive treatment of idiopathic generalised epilepsy


First-line treatment:• offer sodium valproate

• consider lamotrigine, levetiracetam or topiramate if sodium valproate is unsuitable or not tolerated

Adjunctive treatment:• offer lamotrigine, levetiracetam, sodium valproate or topiramate

• if 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.

Treatment of juvenile myoclonic epilepsy


First-line treatment:

• offer lamotrigine or sodium valproate • consider carbamazepine and oxcarbazepine.

Adjunctive treatment:

• offer clobazam, lamotrigine, levetiracetam, sodium valproate or topiramate.

Treatment of epilepsy with GTC seizures only


First-line treatment:• offer ethosuximide or sodium valproate

• offer lamotrigine if ethosuximide and sodium valproate are unsuitable, ineffective or not tolerated.

Adjunctive treatment:• if ineffective consider a combination of two of the above three

• if ineffective 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.

Treatment of childhood absence epilepsy, juvenile absence epilepsy or

other absence 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.

Other epilepsy syndromes

[2012] To go back to syndrome type slide click here

• Maintain a high level of vigilance for treatment-emergent adverse effects.

• Continuing AED therapy should be planned by the specialist.

• Take the person’s needs into account.

• If management is straightforward, continuing AED therapy can be prescribed in primary care.

• Regular monitoring of blood tests is not recommended as routine.

Continuation of pharmacological treatment

[2004]

[2012]

• The decision to withdraw should be made by the person with epilepsy (and their family/carers as appropriate) and the specialist after a discussion of the risks and benefits.

• When AED treatment is being discontinued, it should be carried out slowly.

• Particular care should be taken when withdrawing benzodiazepines and barbiturates.

• There should be a fail-safe plan.

Withdrawal of pharmacological treatment

[2004]

Refer children and young people with epilepsy whose seizures have not responded to appropriate AEDs to a tertiary paediatric epilepsy specialist for consideration of the use of a ketogenic diet.

Ketogenic diet

[2012]

This is indicated for use as an adjunctive therapy in reducing the frequency of seizures in people who are refractory to antiepileptic medication but who are not suitable for resective surgery.

Vagus nerve stimultaion

[2012]

• Give immediate emergency care and treatment.

• Only prescribe buccal midazolam or rectal diazepam to people who have had a previous episode of prolonged or serial convulsive seizures.

• Administer buccal midazolam. Administer rectal diazepam if preferred or if buccal midazolam is not available.

• If intravenous access is already established and resuscitation facilities are available, administer intravenous lorazepam.

First-line treatment of prolonged or repeated convulsive status seizures in the community

[2012]To go back to seizure/syndrome

type slide click hereFor more recommendations

on this click here

Call an ambulance, particularly 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

• there are concerns or difficulties monitoring the person’s airway, breathing, circulation or other vital signs.

First-line treatment of prolonged or repeated convulsive

status seizures in the community: 2


type slide click here

• Secure airway, give high-concentration oxygen, assess cardiac and respiratory function, check blood glucose levels, and secure intravenous access in a large vein.

• Administer intravenous lorazepam. Administer intravenous diazepam if intravenous lorazepam is unavailable. Administer a maximum of two doses of the first-line treatment.

• If seizures continue, administer intravenous phenobarbital or phenytoin.

Convulsive status epilepticus in hospital



• Administer intravenous midazolam, propofol or thiopental sodium to treat adults.

• Administer intravenous midazolam or thiopental sodium to treat children and young people.

• Regular AEDs should be continued at optimal doses and the reasons for status epilepticus should be investigated.

• An individual treatment pathway should be formulated.

Refractory convulsive status epilepticus

[2012]



• Give women and girls and their partners, as appropriate, accurate tailored information and counselling about contraception, conception, pregnancy, caring for children and breastfeeding, and menopause.

• Discuss with women and girls of childbearing potential the risk of AEDs causing malformations and possible neurodevelopmental impairments in an unborn child.

Women and girls: 1

[2012]

[2004]

• Be aware of the latest data on the risks to the unborn child associated with AED therapy when prescribing.

• All women and girls on AEDs should be offered 5 mg per day of folic acid before any possibility of pregnancy.

• Refer to the SPC and BNF for individual drug advice on the interactions between AEDs and hormonal replacement and contraception.

Women and girls: 2

[2012]

[2004]

[2012]

• The possibility of interaction with oral contraceptives should be discussed and an assessment made as to the risks and benefits of treatment with individual drugs.

• The risks and benefits of different contraceptive methods, including hormone-releasing IUDs, should be discussed.

• If a woman or girl taking enzyme-inducing AEDs chooses to take the combined oral contraceptive pill, guidance about dosage should be sought from the SPC and current edition of the BNF.

Contraception: 1

[2004]

• The progestogen-only pill and progestogen implant is not recommended as reliable contraception in those taking enzyme-inducing AEDs.

• The use of additional barrier methods should be discussed with those taking enzyme-inducing AEDs and oral contraception or having depot injections of progestogen.

• The type and dose of emergency contraception should be in line with the SPC and current edition of the BNF.

Contraception: 2

[2004]

• Discuss with those who are taking lamotrigine that the simultaneous use of any oestrogen-based contraceptive can result in a significant reduction of lamotrigine levels and lead to loss of seizure control.

• When a woman or girl starts or stops taking these contraceptives, the dose of lamotrigine may need to be adjusted.

Contraception: 3

[2012]

• Aim for seizure freedom before conception and during pregnancy but consider the risk of adverse effects of AEDs and use the lowest effective dose of each AED, avoiding polytherapy if possible.

• Do not routinely monitor AED levels during pregnancy. If seizures increase or are likely to increase, monitoring AED levels may be useful when making dose adjustments.

Pregnancy

[2004]

• Enable those who have learning disabilities to take an active part in developing a personalised care plan.

• Ensure adequate time for consultation to achieve effective management.

• Do not discriminate but offer the same services, investigations and therapies as for the general population.

Management of epilepsy in those with learning disabilities

[2012]

• Always consider a young person’s physical, psychological and social needs.

• During adolescence a named clinician should assume responsibility for the ongoing management of the young person and ensure smooth transition of care to adult services.

• The information given to young people should cover epilepsy in general and its diagnosis and treatment.

Young people

[2004]

• Do not discriminate against older people.

• Pay particular attention to pharmacokinetic and pharmacodynamic issues with polypharmacy and comorbidity in older people with epilepsy.

• Consider using lower doses of AEDs and, if using carbamazepine, offer controlled-release carbamazepine preparations.

Older people

[2012]

Costs and savings

There is uncertainty around current practice for

pharmacological treatment of epilepsy and how clinicians will

respond to the recommendations. Local commissioners are

encouraged to talk to providers to establish current practice

and how this might change after publication of the guideline.

Depending on current practice, the recommendation on

administering buccal midazolam or rectal diazepam for use in

the community for children, young people and adults who have

had a previous episode of prolonged or serial convulsive

seizures may result in a significant change in resource use in

the NHS.

Discussion

• How does our current prescribing practice compare with that recommended within this guideline?

• Do we have clinical nurse specialists in epilepsy and do all children young people and adults with epilepsy have access to epilepsy nurses?

• Are there any gaps?

• Who is responsible for taking this forward and what action do we need to take?

NICE Pathway

The NICE epilepsy Pathway covers:

•diagnosis

•information

•investigations

•treatment and management

Click here to go to NICE Pathways

website

Image of the pathway overview

NHS Evidence

Visit NHS Evidence for the best available evidence on all aspects of epilepsy

Click here to go to the NHS Evidence

website

NPC tools

Visit the National Prescribing Centre for further resources on epilepsy

Click here to go to the NPC tools

Find out more

Visit www.nice.org.uk/guidance/CG137 for:

•the guideline •‘Understanding NICE guidance’•costing statement•audit support and baseline assessment tool•pharmacological treatment tables•clinical case scenarios•online educational tool.

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Guia NICE epilepsia