EasternPaediatricEpilepsyNetwork

Clinical Guideline

Please note. These guidelines have been reviewed by members of the Eastern Paediatric Epilepsy Network and are believed to be accurate at the time of writing. They are intended to form the basis of guidelines specific to the various trusts and PCTs across the eastern region. Before local adoption these guidelines should be assessed and approved by the guideline development apparatus of each organisation.

Date: August 2008

Due for review: August 2011

Written by: Richard Beach August 2008

How and when to stop anti-epilepsy drugs

This guideline concerns stopping anti-epilepsy drugs (AED) in children who are well free of epileptic seizures on medication.

Quick reference guideline

Objective

  • To provide a rational basis for stopping AED therapy in children who are well controlled on medication and may have “grown out” of their epilepsy.
  • To clarify the practicalities of stopping AED treatment.

Rationale

What is the risk of seizure recurrence?

Epilepsy starting in childhood is not necessarily life long. There are a number of epileptic syndromes of childhood that seem to be age related with a good long-term prognosis. Children who have been 2 years seizure free on medication have a 7 in 10 chance of remaining seizure free if their AEDs are withdrawn. This is well illustrated by the large Camfield1 study, but many other studies have given similar results. This is of course an overall figure and it would be good to give each young person and their family a more specific and personalised recurrence risk.

Table 1 Risk of seizure recurrence on stopping AEDs after 2 years of seizure freedom.

Risk factor / Recurrence risk (%)
Benign childhood epilepsy with centritemporal spikes. / 0
Childhood absence epilepsy / 19
Overall risk including all risk factors / 30
Any EEG abnormality / 39
Idiopathic generalised epilepsy / 40
Multiple seizure types in same patient
Remote symptomatic seizures / 50
Over 14 years at presentation / 70

Table constructed from data in references 2,3,4,5

Table 1 highlights some adverse prognostic features but these may be hard to apply in the individual case. For example Marcus6found that 17 of 29 children with learning difficulties remained seizure free off medication.

Assumptions are made in the literature about the prognosis in particular syndromes. Childhood absence epilepsy is said to remit in 90% of cases, BECTS is described as “largely benign” whereas JME requires lifelong therapy. Specific evidence for individual syndromes is lacking. The figures for recurrence risk in individual sydromes in table1 are based on small numbers from Shinnar et al2.

Little is known of the risks of recurrencefor those who reach 2 years of seizure freedom for the second time.

When do seizure recurrences occur?

Of those young people who suffer seizure recurrence one half suffer a further seizure within 6 months of stopping their AEDs. It seems reasonable to concentrate advice on first aid and safety into that period. See table 2.

Table 2

Take 100 young people with an epilepsy and 2 years seizure free on treatment.
Stop their treatment.
  • 85 will be seizure free 6 months later.
  • 76 will be seizure free 2 years later.
  • 73 will be seizure free 5 years later.
  • 71 will be seizure free 10 years later.
Modified from Shinnar et al7.

Families are often concerned that if there is seizure relapse on stopping treatment it may be difficult to re-establish control. There is evidence that only 1% of young people suffer difficult relapses of this sort8.

There is little evidence on the speed of drug withdrawal. One study9 showed no difference in seizure recurrence comparing 6 weeks and 9 months as withdrawal times. It is thought that Phenobarbitone and some benzodiazepines require careful and prolonged weaning.

Broad recommendations

1)Plan in advance. For young people who have achieved seizure freedom on AEDs it is good practice to set a goal for therapy. Young people and their families can be told from early in treatment that if they remain seizure free then stopping treatment will be discussed after 2 years. This should mean that families will know in advance that stopping treatment will be discussed at a particular appointment. It is important that young people realize that all seizures “count” including absences and myoclonic jerks.

2)Review the case and attempt an estimate of the chance of seizure recurrence on stopping treatment. Two years of seizure freedom is a good prognostic marker and there is a chance of seizure freedom even with those with adverse features in the history – see table 1. For example a patient with learning difficulties may still have a 4 in 10 chance of remaining seizure free off medication. Probably the only group where stopping treatment under the age of 18 years need not be, considered are those with JME.

3)Discuss stopping treatment with young people and their families.

  1. Communicate the risk of seizure recurrence.
  2. Ascertain the views of the young person.
  3. Deal with any particular anxieties
  4. Recommend a trial of stopping treatment unless there are strong adverse factors.

4)If there is agreement on stopping treatment devise a management plan to include the following:

  1. When to begin the AED reduction. It is best to avoid exams, stress points and overseas holidays. Some families like to start drug reduction during the school holidays.
  2. How to reduce AEDs. A typical regime involves weekly drug dose reduction over 8-12 weeks. The NICE guidance suggests “Particular care should be taken when withdrawing Phenobarbitone or benzodiazepines (may take up to six months or longer) because of the possibility of drug related withdrawal symptoms and/or seizure recurrence.”
  3. Revision of first aid and safety advice. (see: Whilst seizure recurrence will usually revisit previous seizure types there is a small risk of emergence of tonic clonic seizures and families should be warned.
  4. What to do in the event of seizure recurrence. This advice will depend on the nature of the epilepsy. Sometimes a single seizure may be an indication to restart AED’s. On the other hand emergence of an occasional absence in CAE may require no further therapy. Details of a relapse plan should be agreed so that families and GPs know what to do in the event of further seizures.
  5. It is helpful for young people/parents to have a contact number for advice in the event of further seizures or other events.

5)Make a follow up plan. A further clinic appointment is usually not necessary. Telephone contact to confirm that all is well may be helpful

6)Fifteen and sixteen year olds – a special case? Whilst for younger children a seizure recurrence can be upsetting, frightening, embarrassing or uncomfortable, for young people on the verge of college, driving or employment the stakes may be still higher. They need to know that they will not be able to get a provisional driving license for a year after a seizure recurrence and employment prospects are diminished by recent seizures. On the other hand if they do not attempt to stop their AED’s there may be a 7 out of 10 chance that they continue treatment unnecessarily for years into adult life. This dilemma is particularly pertinent to girls for whom both contraception and childbirth will be complicated by continuing AED treatment.

Audit standards derived from this guideline

Numbers of children/young people reaching 2 years seizure freedom where there is:

1)Evidence in notes of an estimate of recurrence risk on stopping AEDs

2)Evidence in notes of a discussion with the family about stopping AEDs. This should include information on driving where this is relevant.

3)Evidence of a management plan on stopping AEDs which includes:

  1. When to stop
  2. How to stop
  3. First aid and safety advice

References

1)Camfield C, Camfield P, Gordon K, Smith B, Dooley J. Outcome of childhood epilepsy: A population-based study with a simple predictive scoring system for those treated with medication. J Pediatrics1993; 122:861-8

2)Shinnar S, Berg AT, Moshe SL, Kang H, O’Dell C,Alemany M, Goldensohn ES, Hauser WA. Discontinuing Antiepileptic Drugs in Children with Epilepsy: A Prospective Study. Ann Neurol 1994;35:534-545

3)Dooley J, Gordon K, Camfield P, Camfield C, Smith E. Discontinuation of anticonvulsant therapy in children free of seizures for 1 year: A prospective study. Neurology 1996; 46:969-974

4)Berg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs: a meta-analysis. Neurology1994;44: 601-608,

5)Greenwood, RS, TennisonMB. When to start and stop anticonvulsant therapy in children. Arch Neurol. 1999; 56:1073-1077

6)Marcus JC. Stopping antiepileptic therapy in mentally-retarded, epileptic children. Neuropediatrics 1998; 29:26-8

7)Shinnar S, O’Dell C, Berg AT. Long term prognosis following discontinuation of antiepileptic drug therapy in childhood – onset epilepsy. Epilepsia 2004; 45:365

8)Camfield P, Camfield C. The frequency of intractable seizures after stopping AEDs in seizure-free children with epilepsy. Neurology 2005; 64:973-975

9)Tennison M, Greenwood R, Lewis D, Thorn M. Discontinuing antiepileptic drugs in children with epilepsy: a comparison of a six-week and a nine-month taper period. New England Journal of Medicine 1994;330:1407-1410

Richard Beach.

Norfolk and Norwich University Hospital NHS Foundation Trust