Drug treatment of epilepsy

British Medical Journal, Jan 9, 1999 by Morgan Feely

It is conventional to speak of someone having epilepsy, but it might be better--particularly in relation to promoting better drug treatment--if we were to think in terms of one of the epilepsies. Appropriate management requires not only that doctors differentiate between epilepsy and other similar attacks but also that they identify correctly patients' seizure types and, in some cases, the syndrome (for example, juvenile myoclonic epilepsy). A detailed discussion of the differential diagnosis is outside the scope of this review. However, it is worth emphasising that the diagnosis is usually made from the description of the episodes obtained from the patient or eyewitnesses, or both. This information is often, but not always, supported or supplemented by findings from electroencephalography. Information on diagnosis, investigations, and general principles of treatment can be found in textbooks,[1 2] and videos illustrating different types of seizure are now fairly readily available. Ideally, the diagnosis should be made or confirmed by a specialist, who will also advise on treatment. Nonetheless, doctors who do not have a specialist interest in epilepsy will often be required to take a hand in treatment. This brief review is intended primarily for them.

Methods

As a clinical pharmacologist with some training in neurology, I have been running an epilepsy clinic for many years. This review is based on a synthesis of my personal experience, information from published studies, and opinions imparted by other epilepsy specialists in publications and at recent conferences. I have selected references to support important points and to provide access to additional information, including opinion that differs (in shade at least) from my own.

Choosing a drug

Even in this era of evidence based medicine, there is an art as well as a science in choosing the best drug treatment for patients with epilepsy. The choice of treatment needs to be matched to the patient--for example, whether they are pregnant or potentially childbearing, elderly, or overweight--and to the type(s) of seizure they have (table 1). Often, the most suitable treatment for an individual can be established only by a process of trial and error. Table 2 gives an overview of the current drugs used in treating epilepsy.

Table 1 Choices for early treatment of the more common types
of epilepsy

Seizure type                        Drug(s) of choice

Partial seizures                    Carbamazepine(*) or valproate

                                    Lamotrigine?([dagger])

Generalised tonic-clonic (grand
 mal) seizures:

  Secondary to partial seizures     As for partial seizures

  With absences or/and myoclonic
   seizures                         Valproate

  Without evidence of other
   seizure type(s) or
   focal onset([double dagger])     Valproate[sections] or
                                     carbamazepine

                                    Lamotrigine?([dagger])

Absence (petit mal) seizures        Valproate

Seizure type                        Alternative drug(s)

Partial seizures                    Valproate
                                    Carbamazepine
                                    Lamotrigine

Generalised tonic-clonic (grand
 mal) seizures:

  Secondary to partial seizures     As above

  With absences or/and myoclonic
   seizures                         Lamotrigine

  Without evidence of other
   seizure type(s) or
   focal onset([double dagger])     The other or
                                    lamotrigine

Absence (petit mal) seizures        Ethosuxemide or
                                    lamotrigine

Seizure type                        Reasons for using (examples)

Partial seizures                    Elderly patients
                                    Women taking contraceptive
                                     pill
                                    Carbamazepine "failures"

                                    Obese patients
                                    Valproate failures

                                    Carbamazepine or valproate
                                     not suitable
                                    Childbearing women

Generalised tonic-clonic (grand
 mal) seizures:

  Secondary to partial seizures     As above

  With absences or/and myoclonic
   seizures                         Valproate not suitable
                                    Childbearing women

  Without evidence of other
   seizure type(s) or
   focal onset([double dagger])     As for patients with partial
                                     seizures (above)

                                    As for patients with partial
                                     seizures (above)

Absence (petit mal) seizures

(*) Some studies[18] (but not all[19]) suggest that carbamazepine is somewhat more effective than valproate for partial seizures.

([dagger]) Specialists, familiar with the drug, now (sometimes) use lamotrigine as a first choice.

([double dagger]) Electroencephalogram may be normal or show an abnormality that suggests "primary generalised" epilepsy.