Anticonvulsants used for Focal Seizures

Focal seizures (now referred to as focal rather than partial) originate in a focal region of the cortex and can be subdivided into those that do not impair consciousness (simple focal) and those that do (focal dyscognitive seizures). Both types of focal seizure can spread rapidly to other cortical areas, resulting in secondary generalised tonic-clonic (GTC) seizures.^[1]

Relevant separate articles include Epilepsy in Children and Young People, Epilepsy in Adults and Epilepsy in Elderly People.

Simple focal seizures

• Presentation depends on the site of origin of the discharge - eg, those arising from the motor cortex cause rhythmic movements of the contralateral face, arm or leg (Jacksonian seizures).
• Seizures arising from sensory regions or areas responsible for emotions and memory may produce olfactory, visual or auditory hallucinations, feelings of déjà vu or jamais vu, fear, panic or euphoria.

Focal dyscognitive seizures

• An epileptic seizure that is limited to one cerebral hemisphere and causes impairment of awareness or responsiveness.
• Temporal lobe epilepsy may be simple focal seizures without loss of awareness (with or without aura) or focal dyscognitive seizures (with loss of awareness).

Antiepileptic drugs used for focal seizures^{[1, 2]}

Not all epilepsy is lifelong and it is defined as having resolved when people have remained seizure-free for more than ten years, with no drug treatment for at least five years. Approximately 70% of all adults and children with epilepsy will go into remission. The chances of remission vary with the type of epilepsy, the response to antiepileptic drugs (AEDs) and the frequency of seizures. Withdrawal of medication, if wanted, should be done slowly, with the acknowledgement that it always carries a risk of further seizures.^[3]

The National Institute for Health and Care Excellence (NICE)^[1] advice on treatment of focal seizures is as follows. Unsuccessful treatment is defined as treatment which either does not reduce or stop seizures, or has intolerable side-effects.

• First-line treatment: offer lamotrigine or levetiracetam, moving to the other of these two drugs if the first one tried is unsuccessful.
• If both of these first-line monotherapies are unsuccessful, consider a second-line monotherapy option, choosing between carbamazepine, oxcarbazepine or zonisamide. Try all of these three in turn if the first one is unsuccessful.
• Consider lacosamide as third-line monotherapy if all the second-line drugs are unsuccessful.
• If monotherapy is unsuccessful, consider any of the drugs listed above, or topiramate, as first-line add-on options, considering other drugs from this list if the first one tried is unsuccessful.
• If all of the first-line add-on therapies are unsuccessful, consider second-line add-on therapies brivaracetam, cenobamate,^[4] eslicarbazepine acetate, perampanel, pregabalin or sodium valproate (within MHRA guidance on pregnancy). At this point, management in a tertiary service should be considered and NICE makes this mandatory if cenobamate is used.
• Third-line add-on treatments include phenobarbital, phenytoin, tiagabine and vigabatrin.
• Be aware that some drugs used in clinical practice can exacerbate seizures in those with absence or myoclonic seizures, including juvenile myoclonic epilepsy.

Interactions^[5]

• Interactions between AEDs are complex and may enhance toxicity without a corresponding increase in antiepileptic effect.
• These interactions are very variable and unpredictable.
• Changes in medication should therefore always be done by a neurologist.

Initiation of drug treatment^{[1, 2]}

• AED therapy should only be started once the diagnosis of epilepsy is confirmed, except in exceptional circumstances. AED therapy should be initiated by a specialist.
• Treatment with AED therapy is generally recommended after a second epileptic seizure. AED therapy should be considered and discussed after a first unprovoked seizure if:
  • There is a neurological deficit.
  • The electroencephalograph (EEG) shows unequivocal epileptic activity (however a normal EEG should not be used to exclude the diagnosis of epilepsy, and should prompt consideration of a sleep-deprived EEG).
  • The patient or their family or carers consider the risk of having a further seizure unacceptable.
  • Brain imaging shows a structural abnormality.
• The dose of each medication should be titrated slowly to the maximally tolerated dose or the maximum level as recommended in the British National Formulary. The effect may be monitored by patient-recorded seizure frequency.
• Formulations of AEDs are not interchangeable and generic substitution should not be routinely made. Routine switching between different manufacturers of AEDs should be avoided.

Continuation of drug treatment^{[1, 2]}

• Maintain a high level of vigilance for adverse effects of treatment.
• Continuing AED therapy should be planned by a specialist as part of an agreed treatment plan and the needs of the child, young person or adult and their family and/or carers should be taken into account.
• If management is straightforward, continuing AED therapy can be prescribed in primary care if local pathways and/or licensing allow.
• Adherence to treatment can be optimised with the following:
  • Educating children, young people and adults and their families and/or carers in the understanding of their condition and the rationale of treatment.
  • Reducing the stigma associated with the condition.
  • Using simple medication regimens.
  • Positive relationships between healthcare professionals, the child, young person or adult with epilepsy and their family and/or carers.
• Regular blood test monitoring is not recommended as routine and should be done only if clinically indicated. The pharmacokinetics of some AEDs are non-linear, so specialist knowledge is needed to interpret drug levels. Indications for monitoring of AED blood levels include:
  • Detection or suspicion of non-adherence to the prescribed medication.
  • Uncontrolled seizures.
  • Side-effects.
  • A specific clinical condition needing closer supervision (eg, pregnancy or renal failure).
  • Adjustment of phenytoin dose.
  • Assessment of toxicity.
  • Otherwise unexplained loss of seizure control.

Treatment of drug-resistant epilepsy^[2]

• Drug-resistant epilepsy has been defined as failure to achieve sustained seizure freedom after trials of two tolerated and appropriate AED schedules (as monotherapy or in combination). The majority of patients with newly diagnosed epilepsy respond well to AEDs. Failure to do so may be due to:
• An incorrect diagnosis of epilepsy.
• An inappropriate choice of AED for the epilepsy syndrome.
• Failure to take the prescribed AED.
• An underlying cerebral neoplasm, metabolic condition, or immune process.
• Concurrent drug or alcohol misuse.
• Given a correct diagnosis of epilepsy, failure to control seizures completely with the first well-tolerated AED is a predictor of drug-resistant epilepsy. Once two AEDs have failed as monotherapy the chance of seizure freedom with further monotherapy is low. Improvement in seizure control may be obtained by combining AEDs.
• A range of different AEDs appropriate to the epilepsy syndrome should be added as necessary in sequence, increasing the dose of each slowly to obtain the best response. It may be worthwhile trying the addition of a small dose of a third AED but it may be necessary to accept the persistence of some seizures.
• Failure to respond to appropriate AEDs should prompt a review of the diagnosis of epilepsy and adherence to medication.
• The guidance gives specific regimes for various epilepsy syndromes which are too numerous to list here.

Withdrawal of drug treatment^{[1, 2]}

• The decision to continue or withdraw medication should be taken after a full discussion of the risks and benefits of continuing or withdrawing AED therapy. Withdrawal of AEDs must be managed by, or be under the guidance of, the specialist, after an individualised assessment which considers the risk of seizure recurrence and sudden unexplained death in epilepsy (SUDEP).
• The risks and benefits of continuing or withdrawing AED therapy should be discussed when the person with epilepsy has been seizure-free for at least two years.
• Withdrawal of AED treatment should be carried out slowly (at least 2-3 months) and one drug should be withdrawn at a time.
• Particular care should be taken when withdrawing benzodiazepines and barbiturates (may take up to six months or longer) because of the possibility of drug-related withdrawal symptoms and/or seizure recurrence.
• There should be an agreed plan that if seizures recur, the last dose reduction is reversed and medical advice is sought.
• Discontinuation of medications after epilepsy surgery should be done under guidance from the epilepsy surgery centre.

Special considerations for women and girls of childbearing potential^[6]

In 2018, the MHRA published advice on the use of valproate in women and girls. Valproate must no longer be used in any woman or girl who is able to have children, unless she has a pregnancy prevention programme in place. This is because of the risk of developmental disorders in 40% of pregnancies where the mother is taking valproate, and the 10% risk of birth defects.

A risk acknowledgment form must be filled in by the woman or girl's specialist and filed in the GP notes. This must be done every year.