Drug of first choice for focal epilepsy? The quick and dirty

This question pertains to the discussion yesterday Newly diagnosed focal epilepsy; be prepared for a battle

When selecting an antiseizure medication, there are a few issues that should enjoy priority, including:

1. Efficacy

2. Side effects, including teratogenicity

3. Dosing schedule

4. Cost

Potential efficacy and potential cognitive and mood side-effects weigh most heavily with me in the selection of antiseizure medications for patients. Based upon randomised controlled trials looking at these outcomes and real-world experience, lamotrigine has been my go-to medication for people with focal epilepsy for at least 25 years. When levetiracetam arrived on the scene number of years ago, it quickly became the go-to medication in North America and, if my understanding of it is correct, it is still the antiseizure medication of choice for adults with newly diagnosed focal epilepsy. I suspect that American neurologists are fearful of being sued for Stevens-Johnson syndrome and therefore prescribe levetiracetam more often than lamotrigine, as I can see no other good reason for relegating lamotrigine to second choice. About six or 12 months ago I read an interview with Jacqueline French, one of the pre-eminent epileptologists in the field of antiseizure medications in North America. During the interview she said something along the lines of "levetiracetam is the antiseizure medication that we recommend to neurologists, but when you ask neurologists which medication they would take, lamotrigine is the first choice".

There is a substantial body of scientific evidence regarding the efficacy and side effects of various antiseizure medications; therefore, this forum is not the appropriate place to present that data in detail. You can do worse than reading the following from the Health Technology Assessment group in the UK, which informs UK guidelines. It is a summary of the well-known, pragmatic SANAD randomised controlled trials that were published in the Lancet, if I recall correctly.

Lamotrigine versus levetiracetam or zonisamide for focal epilepsy and valproate versus levetiracetam for generalised and unclassified epilepsy: two SANAD II non-inferiority RCTs | NIHR Journals Library

Lacosamide is my second choice after lamotrigine, except in women of childbearing age, where levetiracetam is currently preferred, but that is a discussion for another day. The above discussion is an oversimplification of a complex topic, which has many nuances. Given the prevalence of drug-resistant epilepsy and the potential for side effects, it is fortunate that we have access to more than 20 antiseizure medications.

Here is a real-world study looking at side effects of commonly prescribed antiseizure medications in adults with newly diagnosed focal epilepsy

The Adverse Effects of Commonly Prescribed Antiseizure Medications in Adults With Newly Diagnosed Focal Epilepsy | Neurology