ANTIEPILEPTIC DRUG IN CHILDREN: WHERE DO WE STAND?
Dr. Utpal Kant Singh*, Dr. B.P. Jaiswal ,MD, DCH**
MD, PhD, FRCPCh (London) FRCP (London) FIAP Nalanda Medical College, Patna *, Department of Pediatrics.**
Seizure is one of the most frequently occurring neurological problem in children of all ages and often poses a challenge to the treating physician in terms of cause, management and prognosis.
  • Seizure is disorder characterized by chronic, recurrent, paroxysmal changes in neurological function and or behavior caused by abnormalities of electrical activity of the brain.
  • Epilepsy: two asymptomatic seizure of at least 24 hrs apart.
  • Convulsion: any seizure accompanied by motor manifestation is known as convulsion.

To Treat Or Not To Treat
The decision to start antiepileptic drugs should be guided by the risk of seizure recurrence and the potential morbidity of antiepileptic drug therapy. According to risk factors, the risk of recurrence after a first unprovoked seizure varies from 23% - 80% 4. The risk is higher in patients with a neurologic insult. Seizure etiology and EEG are the strongest predictors of recurrence 5 - the risk being low (24%) in idiopathic epilepsy and normal EEG and high (85%) in symptomatic epilepsy and abnormal EEG 5. Routine treatment after first unprovoked seizure is not indicated. The decision is to treat should be individualized. In a neurologically normal child with idiopathic generalized tonic-clonic seizure, there is no need to start treatment.

Conditions in which first unprovoked seizure should be treated:

  • Remote symptomatic seizures
  • Children with partial seizure (except rolandic)
  • Prior acute symptomatic seizure
  • Sibling with epilepsy
  • Todd's palsy
  • First seizure during sleep


Monotherapy Versus Polytherapy
The goal or therapy is restoration of a normal life through complete control of seizures using a single drug with least side effects. A single drug is capable to providing satisfactory seizure control in 40-75% of patient with epilepsy.

Advantage of Monotherapy:

  • Less adverse effects
  • No problem of drug interaction
  • Lower cost
  • Better compliance

Initiation and Adjustment of AED(s):
Generally treatment should be started with a small dose of a proper drug to minimize side effects and gradually increased to the anticipated maintenance dose over a few weeks. Starting dose should be half the proposed maintenance dose for the first 1-2 weeks and then give the full dose. Phenytoin can be started with maintenance dose right away. Drug level may be checked after an optimal time (5 times the half life to see if steady state concentration has been reached).
Management Protocol of Refractory Seizures:
The initial drug of choice should be increased to the maximum dose that is tolerated without clinical toxicity (even if the drug level goes above therapeutic range). If still there is no control, a second drug is added and similarly increased. Only when seizures are will controlled, or maximum dose/toxicity is reached, the first drug may be slowly withdrawn.

Choice of Antiepileptic drug according to Seizure type & Epilepsy syndrome
Type of seizures epileptic syndrome

First choice AED

Second choice AED Consider
Partial seizures with/without generalization Carbamazepine
   Phenytoin
Valproate
   Phenobarbitone
   Lamotrigine
   Gabapentin
   Vigabatrin
Clobazam
Generalized tonic clonic seizures Valproate
   Phenytoin
   Carbamazepine
Phenobarbitone
   Primidone
Clobazam
   Felbamate
   Lamotrigine
   Gabapentin
   Tiagabine
   Vigabatrine
Absence seizure Valproate
   Ethosuximide
Clobazam   Lamotrigine  
Juvenile myoclonic
epilepsy
Valproate Phenobarbitone
Progressive myoclonic
epilepsy
Valproate Carbamazepine
Lennox Gastaut syndrome Valproate Clobazam
    Lamotrigine
Clobazam
   Felbamate
   Topiramate
Infantile spasm ACTH or oral   steroid Vigabatrin Benzodiazepines
   Felbamate
   Topiramate
Rolandic epilepsy Carbamazepine
   Valproate
Phenytoin  


If both drugs are ineffective in maximally tolerated doses, only then polytherapy with two drugs should be initiated .Using more drugs normally does not help: on the other hand, toxicities increase.
The possibility of pyridoxine dependency should be considered in every child with refractory seizures up to the age of two years, including those with infantile spasms. This diagnosis can be confirmed by giving 50-100 mg of intravenous pyridoxine under EEG control, during clinical seizure activity. A positive response is seen within minutes to hours and should be followed by an oral maintenance dose of 50-1000 mg/day.
Steroids, deep brain stimulation and ketogenic diet are sometimes used in refractory seizures particularly in Lennox Gastaut syndrome. The other drugs that may be tried are adjunctive drugs, namely, acetazolamide and newer AEDs. Some children with refractory seizures my benefit from surgery which is available only in specialized epilepsy surgery units.
In general, if there is no satisfactory response within three months, it is advisable to refer the patient to an expert.


Indications of Antiepileptic Drug Monitoring
Drug dosage should be determined clinically by the degree of seizure control and the appearance of side effects. It should never be adjusted up and down to keep blood level in the therapeutic range. Therapeutic ranges are more useful for phenytoin, carbamazepine and phenobarbitone, and less useful for valproate. Indication for getting drug levels include:

  • If seizures are not controlled inspite of using maximum dose of appropriate AED (look for trough levels);
  • If seizures recur in a well controlled child where compliance is ensured;
  • Symptoms or signs of AED toxicity (look for peak level);
  • In polytherapy when an AED is being added or discontinued;
  • When it is not clear if clinical deterioration is related to disease or drug;
  • Regimen (dose, drug or other medication);
  • Significant systemic diseases that may alter the drug metabolism, for example, renal or hepatic failure; and
  • Detection of non compliance.
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Singh K U D, DCH , J B D.. Available From : http://www.pediatriconcall.com/fordoctor/ Conference_abstracts/report.aspx?reportid=457
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