The cornerstone of treating epilepsy is regular, long-term pharmacotherapy to eliminate seizures without significant adverse effects.
Antiepileptic pharmacotherapy should be started as soon as the risk of recurring epileptic seizures has been established and epilepsy has been diagnosed.
It is more important to monitor the patient's general status and mental health than laboratory values.
The diagnosis of epilepsy, aetiological investigations, choice of medication and follow-up of response to medication and its suitability are done in a neurology unit in specialized care.
Long-term follow-up of adults with well controlled epilepsy can be carried out in primary care.
Patients with severe epilepsy should be monitored in specialized care. The possibilities for surgical treatment should be assessed sufficiently early in a centre specializing in epilepsy surgery.
General remarks
An epileptic seizure is a transient disturbance in brain function that is due to abnormal, excessive or synchronized electrical neuronal activity in brain areas of varying size.
Epilepsy is a disease in which the brain has a chronic tendency to spontaneously produce epileptic seizures, and patients may additionally have other problems in neurological, cognitive, mental or social performance in consequence of the disease.
With medication, about 70% of the patients become seizure-free while 20-30% of patients have treatment-resistant epilepsy.
Epilepsy is classified as treatment-resistant if despite two appropriately chosen and used antiepileptics there are significant epileptic symptoms affecting daily life, such as repeated seizures, cognitive or behavioural problems, delayed development or adverse treatment effects.
Patients with epilepsy have a 2-3-fold risk of death compared to the normal population. Treatment-resistant epilepsy increases the risk of sudden unexpected death in epilepsy (SUDEP).
Treatment should be provided considering not only the actual seizures but also the aetiology of the epilepsy and the available treatments. The patient's situation should be considered comprehensively, taking into account any effects of the disease on his/her functional capacity and any need for medical or vocational rehabilitation.
Chain of treatment
Specialized care is responsible for:
diagnosing epilepsy
choosing antiepileptic medication and monitoring the response to and suitability of medication
deciding on stopping medication
determining the ability to drive or to work, performing assessments for rehabilitation
follow-up during pregnancy; this also applies to patients without seizures
follow-up of patients with seizures or severe epilepsy, and treatment decisions for such patients.
Long-term follow-up of adults with well controlled epilepsy can be done in primary care.
When follow-up is transferred to primary care, a written treatment plan and follow-up instructions should be recorded individually for each patient in the final neurological assessment.
Reactivation of seizures, challenges or adverse effects related to pharmacotherapy, an active wish to get pregnant or pregnancy are indications for referral for reassessment in specialized care.
Assessment of the treatment of severe epilepsy should be done in a tertiary care hospital. Assessment related to epilepsy surgery should be performed in a centre specializing in such surgery.
Find out about locally relevant chain of treatment.
Pharmacotherapy
The goal of drug therapy is absence of seizures without significant adverse effects.
Find out about local reimbursement policies concerning antiepileptic drugs.
Choice and follow-up of pharmacotherapy
Epilepsies are divided into focal and generalized epilepsies based on type of seizure.
Antiepileptic treatment should be started with a primary drug chosen depending on the type of epilepsy and seizure (see Antiepileptic drugs).
Some drugs, such as oxcarbazepine and carbamazepine, are only suitable for focal epilepsy, but most drugs are broad spectrum drugs effective against all types of epilepsy and seizures. However, the response varies individually.
The aim is to find the lowest effective dose that prevents seizures. The dose should always be tailored individually.
Patients should be contacted 2-8 weeks after beginning medication to assess the response and any adverse effects.
Freedom from seizures and tolerability of the medication are most important, not serum drug concentrations Therapeutic Monitoring of Antiepileptic Drugs for Epilepsy. Drug concentrations rarely need to be monitored in long-term follow-up.
At the beginning of treatment and when increasing the dose, safety blood tests (basic blood count with platelet count, Na, ALT) should be done for oxcarbazepine, carbamazepine, valproate and phenytoin, for example. Routine follow-up with safety blood tests is not needed.
If seizures continue despite medication, a combination of several drugs may be necessary. Combination therapy aims to combine the different mechanisms of action of various drugs, avoiding drugs with similar adverse effects, and utilizing their secondary indications in the treatment of concomitant diseases, such as migraine or neuropathic pain.
Some antiepileptic drugs have numerous interactions, which should be considered when planning other medication.
As antiepileptic medication (enzyme inducers, in particular) is associated with an increased risk of osteoporosis, use of vitamin D is recommended.
Adverse effects
In the starting and escalation phases, adverse effects often occur, particularly CNS effects (fatigue, dizziness, nausea) that are usually mild and subside spontaneously within a few weeks (for more detail, see Antiepileptic drugs).
Such effects can often be alleviated by starting the medication at a low dose and gradually increasing the dose.
When starting medication, symptoms suggestive of rare severe adverse effects should be discussed with the patient, and the patient should be advised to contact the treating unit immediately should such symptoms occur. Particularly symptoms requiring change of medication should be mentioned:
hypersensitivity reactions (rashes)
symptoms of liver damage (vomiting, abdominal pain)
Drugs may cause abnormal blood levels. Mild leucocytopenia (up to 2 × 109 /l), increased liver enzyme concentrations (ALT up to 2-3 × lower limit of reference range) and mild hyponatraemia (Na 128-135 mmol/l) are common, not predictive of more severe adverse effects and, if asymptomatic, do not warrant further measures. Levels differing significantly from the reference ranges are indications for changing medication.
Antiepileptic drugs
Antiepileptic drugs are divided into first- and second-line drugs according to clinical and reimbursement criteria.
Find out about local reimbursement policies and their possible impact on the division indicated below.
Here, we list for each drug the principal mechanisms of action, the types of epilepsy/seizures for which they are most suitable, the initial doses and target maintenance doses, the most common adverse effects and other issues to be observed. Use locally available drug information sources for more detailed information.
Principal mechanism of action: sodium channel blockade
Type of seizure: focal onset seizures
Initial dose: 100 mg twice daily, usually started as emergency treatment with administration of an intravenous loading dose of fosphenytoin; for long-term use only in special cases
20-30% of epilepsies are classified as treatment-resistant, with seizures continuing despite two appropriately chosen and used antiepileptic drugs.
Epilepsy not responding to medication is in most cases severe but the problem may also be an incorrect diagnosis, other disease preventing implementation of the treatment or problems related to adherence to the treatment.
Patients with severe epilepsy should be referred to a tertiary care hospital neurology unit for consultation. A multiprofessional team specialized in epilepsy can perform more detailed investigations to confirm the type of epilepsy and seizure and to define the aetiology in more detail so as to be able to offer the patient the most effective possible treatment.
Some patients with severe focal epilepsy benefit from surgery Surgery for Epilepsy. Surgical treatment aims to stop seizures by excising or isolating the brain area causing epilepsy. Normal imaging findings do not exclude the possibility of epilepsy surgery.
Find out about locally relevant unit(s) that perform assessments for epilepsy surgery.
Löscher W, Potschka H, Sisodiya SM et al. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options. Pharmacol Rev 2020;72(3):606-638. [PubMed]
Brodie MJ. Tolerability and Safety of Commonly Used Antiepileptic Drugs in Adolescents and Adults: A Clinician's Overview. CNS Drugs 2017;31(2):135-147. [PubMed]