Epilepsy is a disorder of the brain where patients who suffer from it have a tendency to have recurrent, unprovoked seizures. A seizure is a sudden, excessive and rhythmic organization of electrical discharges involving a portion of the brain or the whole brain itself. 1 in 10 people will have 1 seizure in a lifetime – usually provoked (i.e. severe sleep deprivation, EtOH withdrawal, sepsis, metabolic abnormalities, drugs, etc). 1 in 100 people live with a diagnosis of epilepsy.
Epilepsy is not just about seizures. I view it as a spectrum of many different types of presentations. Epilepsy also involves personality changes, changes in cognition, changes in sleep, changes in coordination and mood, etc. Epilepsy can be classified into different categories: 1) focal epilepsies – there is a region of the brain or regions of the brain that are hyperexcitable and capable of seizing, 2) generalized epilepsies – whole brain involved with seizures, 3) epileptic encephalopathies – lennox gastaut syndrome, West Syndrome, Dravet syndrome, Rett syndrome – etc – that have both generalized and focal seizures, etc.
Treatment of epilepsy involves management of seizures as well as management of the mood/sleep/personality disorders that often times occur. At present, the goal of antiseizure drug treatment is to use medications that are either pro-inhibitory or anti-excitatory. In this sense, all of the medications must be able to cross the blood brain barrier and with this quality – many AEDs have some untoward side effects.
While epilepsy itself can create difficulties with cognition (most commonly short term memory loss, attention/concentration deficits), the antiepileptic drugs (AEDs) contribute to cognitive dysfunction as well. For example, commonly prescribed medications for seizure control: phenytoin, valproic acid, zonisamide, topiramate, etc all are known to be associated with cognitive side effects. Some of the newer agents – lamotrigine, lacosamide, eslicarbazepine, levetiracetam, brivaracetam may have less effects on overall cognition.
With many refractory epileptic patients, dual, triple or more AED drug combination therapy may play a role in getting seizures under control. In this population, often times high doses of medications are used and with that, there are more chances of untoward side effects. The role of an epileptologist like myself is to find a good balance between optimal seizure control and side effects as the goal of care is to improve the quality of life for patients.
With Anavex’s approach, it seems that they would like to use 2-73 or 19-144 as an adjunct with lower doses of standard antiepileptic medications in order to potentiate the effectiveness of the dedicated antiepileptic medication, prolonging its effect at the channel/receptor it is meant to bind to, and allowing for further cell membrane stabilization in order to decrease neuronal excitability.
With this approach, it would seem that Anavex is making attempts to show efficacy with its use as adjunct to all antiepileptic medications. Perhaps – combining 19-144 or 2-73 with standard AEDs in a refractory epileptic patient may contribute to decreased seizure frequency and allow for improvement in quality of life.
Once more information is publicized by Anavex- I will be sure to make some time to discuss more about the science behind the medications relative to epilepsy care. I look forward to future progress by Anavex. Good luck to all longs!
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