What Is Seizure?
A seizure is an abnormal synchronization and excessive excitation of a population of cortical neurons.
What Is An Epilepsy?
Epilepsy is a tendency towards repetitive seizures unprovoked by acute systemic or neurologic insults.
What Are Antiepileptic Drugs?
Antiepileptic drugs (AEDs) are one of the most common medications used to treat seizure disorders. Antiseizure or antiepileptic drugs are targeted to inhibit neurotransmission, which can be achieved by blocking sodium or calcium excitatory channels, enhancing the inhibitory activity of gamma-aminobutyric acid (GABA), or by blocking glutamate receptors.
The antiepileptic drug decreases the frequency and severity of seizures in people with epilepsy. It can treat the symptom of seizures and not the underlying epileptic condition. The goal of therapy is to maximize the quality of life by minimizing seizures and adverse drug effects.
The first effective AED (Antiepileptic drug) was potassium bromide, discovered in the mid-nineteenth century. Phenobarbital (PHB), which came into use in the early twentieth century, is used to induce sleep and was found to have antiseizure activity and became the drug of choice for many years. Several medications similar to Phenobarbital were developed, including Primidone.
What Is The Pharmacokinetics of Antiepileptic Drugs?
Absorption of Antiepileptic Drugs:
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Absorption is essentially complete for all the Antiepileptic drugs except Gabapentin, which is dose-dependent.
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The absorption timing varies widely by drug, formulation, and patient characteristics.
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Absorption of AEDs is generally slowed by food in the stomach, except Carbamazepine (CBZ) and Lamotrigine, which are not slowed by food.
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Therapeutic levels will usually take several hours.
Elimination of Antiepileptic Drugs:
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Metabolism generally occurs in the liver.
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Excretion is done by the kidneys, both active and inactive metabolites.
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Differences in metabolism - Age and systemic disease.
How To Select An Antiepileptic Drug?
The selection of Antiepileptic drugs is usually based on a range of factors, including:
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Seizure type.
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Age.
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Gender (mainly if you are a woman living with epilepsy and of childbearing age).
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General health.
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How well a person can tolerate the medication.
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Other associated health-related conditions.
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Other medications.
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The impact of seizure activity on a person's life and wellbeing.
It is a common misconception that only neurologists are entitled to prescribe anticonvulsants (antiepileptic agents). The field of psychiatry has utilized antiepileptics in treating a host of conditions, predominantly mood disorders. Anticonvulsants are also used to stabilize the mood of individuals in aggression, personality disorders, and bipolar affective disorder, previously called manic-depressive illness.
Research has shown that some of the routinely used anticonvulsants show great promise in affective disorders. For example, we all know that Sodium Valproate is the first-line agent to treat seizures of all types, except focal seizures, for which Lamotrigine or Carbamazepine are the first-line agents.
Surprisingly, all the three agents mentioned above are utilized to treat a host of neuropsychiatric conditions.
First-Generation AEDs:
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Carbamazepine.
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Ethosuximide.
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Phenobarbital.
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Phenytoin.
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Primidone.
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Valproic acid or Sodium Valproate.
Newer Anticonvulsants:
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The newer anticonvulsants being tried in treating bipolar disorder include Gabapentin, Topiramate, Tiagabine, Felbamate, Eslicarbazepine Acetate, Lacosamide, Oxcarbazepine, Pregabalin, Rufinamide, Stiripentol, Tiagabine, Vigabatrin, and Zonisamide and Levetiracetam.
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However, more large-scale studies are needed before we can routinely use these agents, in the same vein as one uses Sodium Valproate, Lamotrigine, or Carbamazepine.
Sodium Valproate:
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Valproate is the drug of choice in dysphoric mania or irritable mania.
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Mania is a phase in the course of a bipolar disorder patient. The individual is unusually cheerful and jocular, talks at a furious pace that cannot be interrupted, displays high energy levels, is irritable and restless, and has a decreased need for sleep.
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Sodium Valproate or Valproic acid is the agent that is most commonly used in dysphoric mania.
Lamotrigine:
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Similarly, Lamotrigine is used when depressive spells or episodes predominate the illness (bipolar disorder).
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It works wonders, provided it is initiated at a low dose and slowly titrated.
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'Start low, go slow' is a common dictum that one comes across, as far as the usage of Lamotrigine is concerned.
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As much as it is a wonder drug, Lamotrigine can be the harbinger of a fatal skin rash, called the Steven-Johnson syndrome, if titrated rapidly.
Carbamazepine:
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Carbamazepine can be used to treat acute mania if the manic episode is refractory or recalcitrant to Lithium.
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Some clinicians utilize Carbamazepine as a first-line agent also, in treating an acute manic episode.
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Some studies have reported that several factors associated with non-response to Lithium might predict response to Carbamazepine.
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These include dysphoric mania, greater severity of mania, a negative family history of bipolar disorder, and those with greater decrements in thyroxine levels during treatment.
What Are The Uses Of Antiepileptic Drugs?
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Carbamazepine, Lamotrigine, Valproate, and Oxcarbazepine appear to have mood stabilizing properties.
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Gabapentin, Tiagabine, and Pregabalin have anxiolytic benefits.
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Pregabalin, Carbamazepine, Gabapentin, and Oxcarbazepine have been used to treat neuropathic pain like postherpetic neuralgia, and diabetic polyneuropathy.
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Topiramate and Divalproex Sodium have been used in the prophylaxis or acute treatment of migraine.
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Carbamazepine, Oxcarbazepine, Sodium Valproate are effective in acute mania. At the same time, Lamotrigine is effective in acute bipolar depression and prophylaxis but is ineffective in treating acute mania or preventing mania.
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Levetiracetam is promising but needs studies on a larger scale. Topiramate and Gabapentin do not appear to provide benefits in treating core manic or depressive symptoms.
Taking your AEDs as prescribed by your physician is essential for maintaining good seizure control. AEDs will work best when taken at the same time every day, and this will also help to keep the medication at a steady level in the body.
Some reasons why people may not take their AEDs as prescribed by the physician include:
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Forgetting to take a dose.
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Accidental intake of two doses.
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Stopping the medication due to side effects.
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Reduced effect of the medication due to illness (for example, vomiting or diarrhea).
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Using a different brand.
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Running out of medication.
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Stopping the medication without medical advice since the person has not had a seizure for a long time.
Conclusion:
The newer drugs have provided us with improved safety profiles and novel mechanisms of action. This vast choice of AEDs has made it desirable to offer tailored treatment plans based on the patient's unique profile. Even though there is an increase in the selection of medications, we can still only treat the symptoms of seizures. We cannot make any significant progress in reversing or stopping the underlying mechanism of epileptogenesis or offering neuroprotection from epileptogenesis. Therefore, it is not surprising that the prevalence of drug-resistant epilepsy has not improved despite the vast array of AED choices.
