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See letter "Stopping antiepileptic drugs – other factors to consider" in volume 44 on page 78.Patients with epilepsy who have been free of seizures for at least two years may be able to stop their antiepileptic drugs. Discontinuation may be considered after an individualised harm–benefit assessment and consultation with a neurologist is recommended.
It is paramount to discuss with patients whether the risk of seizure recurrence is worth the benefit of stopping the antiepileptic drug.
The risk of seizure recurrence after antiepileptic drugs are discontinued depends on the epilepsy syndrome and a number of other risk factors. Approximately 30–50% of patients will relapse.
If seizures recur, the majority of patients regain seizure control when treatment is resumed. However up to 20% do not achieve immediate remission.
Keywords: anticonvulsants, epilepsyAntiepileptic drugs are effective in stopping seizures in approximately two-thirds of patients with newly diagnosed epilepsy.1 However, it is impossible to know in patients who are seizure-free for a long time whether the absence of seizures is due to seizure suppression by their treatment, or due to remission of the epilepsy.
A decision to continue or to stop antiepileptic drug treatment requires an individualised harm–benefit assessment. The main concern is the recurrence of seizures after treatment stops. A number of factors need to be considered when assessing the risk of recurrence. It is important to include patients in the discussion of whether this risk is worth the benefit of stopping treatment.
Up to 88% of patients experience adverse effects from antiepileptic drugs. These include dizziness, sedation, cognitive and neuropsychiatric symptoms, which can negatively affect quality of life.2 There are also concerns regarding bone health and an increased risk of fractures as a long-term complication with some antiepileptic drugs.3
Women of childbearing age often worry about the potential teratogenicity of antiepileptic drugs. This may be a motivation to attempt to reduce their antiepileptic drugs, ideally long before actually planning a pregnancy. While it is important to limit exposure to teratogenic antiepileptic drugs during pregnancy, abrupt cessation should be avoided. Some antiepileptic drugs have a known (often dose-dependent) risk of teratogenicity. Valproate has the highest risk of major congenital malformations. Other drugs are considered safer with lamotrigine and levetiracetam having the lowest risk.4 For many newer antiepileptic drugs the risk of harm is still unknown.
Antiepileptic drugs, such as carbamazepine and phenytoin, affect important hepatic enzyme systems such as cytochrome P450. They can have significant pharmacological interactions such as reducing the efficacy of oral contraceptive pills, oral anticoagulants (warfarin and direct oral anticoagulants) and direct-acting antiviral drugs for chronic hepatitis C. Patients with chronic hepatitis C are usually required to either taper their therapy or switch to an alternative antiepileptic drug before starting antiviral treatment.
Other reasons for discontinuation may include the cost of treatment. There is also the wish to feel ‘cured’ and to avoid the inconvenience and stigma of taking drugs daily.
The discussion about antiepileptic drug discontinuation should prompt review of the original diagnosis and supporting evidence. Patients with an equivocal history of seizures or patients who never fulfilled the diagnostic criteria for epilepsy (e.g. acute symptomatic seizures or prophylactic use of an antiepileptic drug) should be evaluated again to see if there is any indication for continuing treatment.
It is important to explore the patient’s concerns and motivation for antiepileptic drug withdrawal. There may be alternatives for the patient to consider such as dose reduction or change of antiepileptic drug to address adverse effects, pharmacological interactions or teratogenicity. Some patients may only need clarification and reassurance regarding the safety profile of their antiepileptic drug.
The main risk associated with discontinuing antiepileptic drug therapy is seizure recurrence. This occurs in 26–63% of cases depending on the patient population.5-7 A meta-analysis of 10 studies including 1769 patients with varying characteristics found a seizure recurrence rate of 46% after antiepileptic drugs were stopped.5 The rate of seizure recurrence within the same time period is about twice the rate reported with continued treatment.6,8 The risk is highest within the first 6–12 months after discontinuation, but remains substantially increased for many years.5,6
Seizure recurrence can have devastating physical, psychological and social consequences. These may include injury, loss of self-esteem, stigma around seizures, unemployment and the inability to drive.
Some patients are willing to stop antiepileptic drugs even when the risk of relapse is substantial, whereas others fear the return of seizures and decide to continue their antiepileptic drugs. In one study, more than half of the patients preferred to continue their antiepileptic drug after two years of seizure freedom. They felt well-adjusted to their treatment and were concerned about possible seizure recurrence after withdrawal and the subsequent loss of their driving licence or even their jobs.9
A large meta-analysis identified independent predictors of seizure recurrence after treatment stops (see Boxes 1 and 2 ). The authors of the analysis created an easy-to-use web-based epilepsy prediction tool to assist clinicians when counselling patients. This tool is particularly useful in patients with some predictors in favour and others against stopping treatment. It calculates an individualised risk of seizures in the next two and five years after antiepileptic drug withdrawal, and the chance to be seizure-free after 10 years. The calculator should not be used as a substitute for an individualised discussion of the full range of harms and benefits, but it helps substantially to guide tailored choices by the doctor and patient.
| Long duration of epilepsy before remission Short seizure-free interval before antiepileptic drug withdrawal Older age at onset of epilepsy (in patients >25 years) History of febrile seizures More than 10 seizures before remission Absence of a self-limiting epilepsy syndrome e.g. absence or rolandic epilepsy Developmental delay Epileptiform abnormality on EEG before withdrawal |