Summary

The article summarises the practice guidelines issued by the American Academy of Neurology (AAN), American Epilepsy Society (AES), and Indian Epilepsy Society (IES) for the treatment and management of epilepsy , specifically, use of AEDs and drug interactions and considerations in paediatric and adult patients.

Epilepsy treatment should be started as monotherapy by giving a single standard anti-epileptic drug (AED). The dose of the AED should be increased slowly till seizures are under control with no side effects.

If monotherapy is found to be ineffective, or if the patient is not able to tolerate monotherapy comfortably, another AED can be opted for. The second drug dosage is increased gradually until there are no seizures or till the side effects become tolerable.

The dose of the first drug is then slowly reduced. However, after failing with two attempts of giving monotherapy AED without getting positive seizure control, combination therapy can then be given by adding another AED as "add-on” therapy for seizure control.

Epilepsy treatment may be deferred if the seizures are not very frequent with year-long intervals between seizures, or if they occur very briefly (partial sensory or myoclonic) without any structural anomaly. However, treatment in cases of the first unprovoked seizure can be considered in cases of a prolonged focal seizure, status epilepticus, detection of neurological deficits, a positive family history of seizures, an abnormal EEG, CT or MRI, if there is a possibility of previous seizures confirmed by history taking, and in patients involved in a high risk job or a life endangering activity.

First-Line therapies

• The conventional first line drugs for epilepsy generally include phenytoin (PHT), phenobarbitone (PB), carbamazepine (CBZ), oxcarbazepine (OXC) and valproate (VPA)
• New or second-line drugs for epilepsy include all the other AEDs

Since conventional AEDs are cheaper and there is more familiarity with their side effects even when used for the long term, conventional AEDs are preferred as initial treatment over the new or second-line drugs AEDs. Newer AEDs can be given to patients when they have other illnesses besides epilepsy, and the first line of drugs may be contraindicated due to drug interactions such as is seen with oral contraceptives, anticoagulants, antiretrovirals or immunosuppressants.

Measures to take before beginning AEDs

1. Before giving AEDs, monitoring should be started by doing a complete blood count, liver enzymes and renal function tests.
2. Every year, calcium (Ca++), alkaline phosphatase (ALP) and other tests of bone metabolism should be performed in patients taking enzyme-inducing drugs.
3. Regular follow-up should be provided to epileptic patients and they should be advised to maintain a diary in which they log their episodes of seizures.
4. On the basis of the patients seizures control and their side effects, their first follow up can be fixed for anytime between 2-4 weeks after starting treatment; and the next follow ups can be offered every 3–6 months.

Considerations of drug interactions

1. To understand the drug to drug interactions in epilepsy, a thorough knowledge about the pharmacokinetics of AEDs is essential. The metabolism of lipid-soluble drugs and elevations in hepatic enzymes are induced by some AEDs such as PHT, PB, CBZ and OXC.
2. The oral contraceptive pill (OCP) and oral anticoagulants interact with AEDs too.
3. When AEDs are used with drugs in the theophylline group, erythromycin, ciprofloxacin or ofloxacin or with the antitubercular drugs (isoniazid and rifampicin) , the antiretroviral drugs and mefloquin, vital drug interactions are likely to occur.
4. If no seizures are experienced during 2 to 3 years, then AEDs can be withdrawn based on the type and cause of seizures. A discussion with the patient and their family will also be a good idea so that a mutual decision can be taken.
5. In certain epilepsy syndromes such as juvenile myoclonic epilepsy, withdrawal of AEDs is best avoided since a very strong tendency for recurrence is seen after 6 months or longer after withdrawal.

Considerations in pediatric patients

1. Neonates and infants generally have subtle manifestations of seizures which should be treated very cautiously.
2. Maximum importance should be given in the identification of the seizure type, selection of appropriate drugs and the required dosages. Even though the basic treatment principle is same for all cases, there are some special cases in children.
3. Proper diagnosis, treating an acute event of seizure, prophylaxis for future events and family counseling are included in the management of febrile seizures.
4. The use of rectal liquid diazepam (0.5 mg/kg), or buccal or nasal midazolam (0.3 mg/kg) use should be taught to parents for the acute stoppage of seizures lasting for two minutes or more.
5. In infants, phenobarbitone and in older children, valproate can be given for 1-2 years.
6. As prophylaxis during fever, intermittent 0.75 mg/kg oral clobazam for 2-3 days in two divided doses daily can be given to prevent recurrence of seizures. Prophylaxis of febrile seizures only reduces the recurrence of seizure and not the risk of future epilepsy.
7. Majority of children will need an electroencephalogram and neuroimaging studies such as an MRI of the brain for diagnosis. In cases of traumatic brain injury, a plain CT scan is indicated.
8. A contrast enhanced CT scan is indicated to detect the presence of granuloma in children of age 2 years and above, particularly in those presenting with conditions such as convulsive seizures, focal seizures, and cluster of seizures or focal neurological deficits.
9. Children of any age with signs of postictal focal deficit (Todd's paresis) which do not resolve immediately, or return to baseline within a few hours after the seizure, should be given emergent neuroimaging.
10. All children should have their serum calcium, magnesium, electrolytes and glucose levels monitored.
11. In children suspected to have meningoencephalitis and in febrile infants with suspected meningitis, a lumbar puncture should be done.
12. In cases of West syndrome and infantile spasms, first line treatment is given using corticotropin or corticosteroids. Specialist treatment is recommended for these children.
13. Benzodiazepines, VPA, vigabatrin and topiramate are the second choice of drugs for these conditions.
14. In children with cerebral palsy, mental retardation and learning disability, AEDs can be safely used for epilepsy.
15. Children already affected with prior speech and language problems can cautiously be given PB and topiramate (TPM) keeping in mind that PB is related with hyperactivity and TPM is related with word-finding difficulty.
16. In the acute phase of epilepsy due to acute traumatic brain injury, antiepileptic drugs are needed but can be withdrawn in a week. Antiepileptic drugs can also be withdrawn after 3 months in cases when the patient is having diseases involving the parenchyma such as in CNS tuberculosis, and pyogenic meningitis with parenchymal involvement.

Considerations in adult patients

• The patient should be initially stabilised, after which a neurological examination of the patient and a detailed history should be taken to confirm whether the incident was actually a seizure
• Treatment of a patient who has had a seizure for the first time would depend on the risk of recurrence of seizure, and whether the seizure was provoked i.e. acute symptomatic seizure
• In cases when an adult patient has an unprovoked seizure for the first time, they should be informed that the probability of another seizure recurrence is highest (21–45%) within the first 2 years
• Doctors should counsel and encourage patients for immediate AEDs treatment since this lowers the risk of seizures recurrence of within 2 years following the first seizure
• In a few special clinical conditions, monitoring of blood glucose, blood counts, and electrolyte panels especially sodium can be useful
• In certain clinical situations, a toxicological screening can be useful
• If possible an MRI of the brain, and brain imaging using computed tomography (CT) should be done
• A lumbar puncture is not regularly indicated but it can useful in some definite clinical situations such as if the patient has fever
• In pregnancy, drugs that are given once a day should be used with precautions
• Folic acid at a dose of 5 mg/day should be given to all women with epilepsy (WWE) if they are in the reproductive age group when their AED treatment has commenced
• At 34 and 36 weeks of pregnancy, all WWE should receive 10 mg IM doses of vitamin K unless contraindicated
• If seizures occur during labor, they should be stopped immediately by giving lorazepam in a dose of 4 mg IV or diazepam
• Vitamin K 1 mg IM should be given to all infants born to mothers receiving AED treatment