Anticonvulsants Used For Partial Seizures

Partial seizures originate in a focal region of the cortex and can be subdivided into those that do not impair consciousness (simple partial) and those that do (complex partial). Both types of partial seizure can spread rapidly to other cortical areas, resulting in secondary generalized tonic-clonic seizures.
See relevant articles on managing epilepsy in primary care and in different age groups.

• Simple partial seizures:
  • Presentation depends on the site of origin of the discharge. e.g. 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 deja vu or jamais vu, or fear, panic or euphoria.
• Complex partial seizures:
  • Previously called temporal lobe or psychomotor seizures. They are the most common seizure type in adults and the most difficult to control with treatment. There may be a warning aura immediately preceding loss or reduction of awareness.
  • Complex partial seizures typically last less than 3 minutes. During that time, patients may appear awake, but lose contact with their environment and do not respond normally to instructions or questions.
  • Patients usually stare and either remain motionless or engage in repetitive semi-purposeful behaviour called automatisms, including facial grimacing, gesturing, chewing, lip smacking, snapping fingers, repeating words or phrases, walking, running or even undressing. Patients cannot remember behaving in this manner. If restrained, they may become hostile or aggressive. In some cases it can be difficult for an unexperienced observer to recognising a fit is occurring at all!
  • After a seizure, patients are often sleepy and confused, and complain of a headache. This post-ictal state can vary from minutes to hours.

• Carbamazepine, lamotrigine, sodium valproate and phenytoin can be used in monotherapy for secondarily generalised tonic-clonic seizures and for partial (focal) seizures; alternatively, oxcarbazepine monotherapy can be used. Phenobarbital (phenobarbitone) and primidone are also effective but they are more sedating and are not used as first-line drugs.
• Where a single drug has failed to control the seizures, combination therapy can be tried with the above drugs or with additional drugs, such as gabapentin, tiagabine, topiramate or vigabatrin; alternatives include acetazolamide, clobazam and clonazepam.
• Systematic reviews found no reliable evidence on which to base a choice among antiepileptic drugs in terms of seizure control.
• Other antiepileptic drugs:
  • There are no random controlled trials of other antiepileptic drugs used as monotherapy in people with partial epilepsy.
  • Systematic reviews in people with drug resistant partial epilepsy found that adding gabapentin, levetiracetam, lamotrigine, oxcarbazepine, tiagabine, topiramate, vigabatrin, or zonisamide to usual treatment reduced seizure frequency compared with adding placebo.
  • Adding any of these drugs increases the frequency of adverse effects compared with placebo. There is no good evidence from RCTs on which to base a choice among drugs.

• Interactions between antiepileptics are complex and may enhance toxicity without a corresponding increase in antiepileptic effect.
• Interactions are usually caused by hepatic enzyme induction or hepatic enzyme inhibition.
• Displacement from protein binding sites is not usually a problem.
• These interactions are very variable and unpredictable. Plasma monitoring is therefore often advisable with combination therapy.

• Lamotrigine, controlled-release carbamazepine, topiramate or sodium valproate are options for partial seizures.
• The currently recommended first-line drugs in treating the majority of childhood epilepsies are sodium valproate and carbamazepine.
• Syndromes associated with partial seizures are less common than generalised seizures in children. Carbamazepine is the usual preferred treatment for partial seizures.

Indications for drug monitoring include:

• When drug therapy is initiated and after dosage adjustments (sampling at trough level at steady-state).
• Suspected therapeutic failure: identify inappropriate dosage, non-compliance, altered absorption, altered clearance (sampling at trough level at steady-state).
• Therapeutic confirmation (i.e. after optimum seizure control so that a drug level can serve as a reference point in the event that seizure control is lost or side effect occur) (sampling at trough level at steady-state).
• Signs of clinical intoxication (sampling at peak level or when symptoms are present).
• Suspected drug interaction (sampling at trough level).
• Monitoring of pharmacologically active metabolites.
• Special risk groups where drug pharmacokinetics is altered: neonates, elderly patients, pregnant women, patients with compromised elimination e.g. renal, hepatic disease (sampling at trough level).
• Suspected drug overdose.

• As many as 70-80% of patients on antiepileptic drug treatment will eventually become seizure free
• Because of the possible long-term side effects of the drugs, it is common clinical practice to consider drug withdrawal after a patient has been in seizure free for three or more years.
• The probability of relapse after stopping treatment has varied between 11-41% in different studies. The risk is less for children than for adults. Most relapses occur within the first year of treatment reduction or withdrawal.
• The more severe and long lasting the patient's epilepsy before remission the greater the risk of relapse
• Juvenile myoclonic epilepsy or the presence of a structural lesion underlying the epilepsy also enhance the risk of relapse.
• Whether EEG is helpful is controversial. Only those EEGs taken after a period of remission are likely to be of value. In children there seems little doubt that the presence of persisting EEG abnormalities has an adverse prognostic influence but whether this is true in adults remains uncertain.
• Social complications of failed drug withdrawal increase with adulthood and trials of drug withdrawal should ideally take place before school-leaving age. After this a number of factors may influence the decision, e.g. employment, driving, leisure activities, contraception and pregnancy.
• The final decision to come off drug treatment should be taken by the patients and their families following advice from the physician. If a decision to withdraw medication is made, discontinuation of treatment should be undertaken slowly, possibly over a period of months, to minimise the risks of relapse.