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Anti-epileptic Drug Therapy – Drug Choices

What Are the Best Medications for Seizures – How Long is Epilepsy Treatment – Major Side Effects of Anti-epileptic Drugs

Anti-epileptic Drug Therapy
Statistically, 37% of epilepsy patients become seizure free on the first medication and 47% will become seizure free on subsequent medication(s). The rest will have a variable degree of freedom from epileptic seizures.

Drug therapy, with rare exceptions, depends on the type of epileptic seizures more than on the underlying cause of epilepsy. Some forms of epilepsy have more than one type of seizures. For example, JME might cause myoclonic seizures, absences, generalized tonic-clonic seizures, which limits the choices, because the drug, ideally, has to be effective for all of them. In reality, some medications, while controlling one type of seizures, might worsen other types.

Antiepileptic medications can be divided into broad spectrum (they work for multiple seizure types) and narrow spectrum – those that control only specific types of seizures.

Epilepsy treatment is often lifelong and the choice of medications also depends on additional factors, such as other medical problems and gender. For instance, Valproate is very female-unfriendly drug, especially for childbearing age due to high rate of birth defects.

Anti-epileptic Drug Choice Depends on the Type of Seizures

Treatment of Classical Absences

Ethosuximide is an excellent drug for classical absences. It is appropriate exclusively for Childhood Absence Epilepsy because other types of seizures are unlikely in this form of epilepsy.

Valproate (better) and Lamotrigine are the drugs of choice for all other epilepsy syndromes with absences because of their broad spectrum of activity. Occasionally, however, Lamotrigine may worsen absences.

The following drugs are contraindicated for absences: Oxcarbazepine, Carbamazepine, Tiagabine, Gabapentin, Vigabatrin.

Drugs for Myoclonic Seizures

Levetiracetam and Valproate (avoid in females whenever possible) are the drugs of choice.

Other options: Topiramate, Clobazam, Clonazepam, Felbamate (last resort due to potential side effects). Lamotrigine may be effective in some patients while exacerbating myoclonic seizures in other patients.

Contraindicated in patients with myoclonic seizures: Oxcarbazepine, Carbamazepine, Tiagabine, Vigabatrin

Drug Therapy for Focal Seizures

Carbamazepine, Oxcarbazepine, Eslicarbazepine, Gabapentin, Pregabalin, Tiagabine, Vigabatrin, Lacosamide are all indicated for focal epilepsy with or without secondary generalized seizures. These drugs are narrow spectrum, and they are either not recommended or contraindicated for other types of seizures.

Broad spectrum drugs effective for focal seizures: Valproate, Lamotrigine, Levetiracetam, Topiramate, Zonisamide, Felbamate, Phenobarbital, Primidone, Benzodiazepines

Generalized Convulsive Seizures

Valproate, Lamotrigine, Levetiracetam, Topiramate, Zonisamide, Felbamate, Phenobarbital, Primidone, Benzodiazepines, Phenytoin are broad spectrum drugs. Besides generalized tonic-clonic seizures, they are usually effective for focal epilepsy and some of them work for myoclonic seizures as well.

The full spectrums of effectiveness for Lacosamide, Ezogabine (Reigabine), and Perampanel remain undetermined.

Anti-Epilepsy Drugs for Special Circumstances
Individual ARDs choice may be dictated by additional circumstances:

  • Childbearing age – Avoid Valproate
  • Asians – Avoid Carbamazepine
  • Kidney stones – Avoid Topiramate and Zonisamide
  • Tendency to skin reactions – Avoid Lamotrigine and Carbamazepine
  • Migraine – Topiramate and Valproate are preferred
  • Obesity – Avoid Gabapentin, Pregabalin and Valproate;
  • Topiramate and Zonisamide may offer weight loss as a side effect
  • Depression/Bipolar Disorder – Lamotrigine, Valproate, and Carbamazepine might be beneficial
  • Chronic pain syndrome – Gabapentin, Pregabalin, Carbamazepine, Oxcarbazepine, Lacosamide also used in chronic pain syndromes
  • Polyneuropathy in AIDS – Lamotrigine
Major Anti-epileptic Drugs Side Effects
Please, do not perceive the following information as a complete listing of side effects. Only the most devastating and most common side effects are mentioned here.

  • Valproate – birth defects, acute hemorrhagic pancreatitis, thrombocytopenia, liver toxicity, elevated ammonia, hair loss, tremor, weight gain, nausea, vomiting
  • Lamotrigine – Stevens-Johnson syndrome especially in children, in combination with Valproate and rapid dose increase
  • Topiramate – acute glaucoma, kidney stones, liver failure, decreased sweating leading to heat shock at high air temperatures, metabolic acidosis, numbness and tingling are common, feeling dull and drowsy – “zombie-like”, weight loss
  • Levetiracetam – dizziness, sleepiness, fatigue, depression, psychosis, behavioral problems
  • Carbamazepine – Stevens-Johnson syndrome, hyponatremia, low white blood cells, liver toxicity, rash, weight gain, nausea, dizziness, drowsiness, double vision
  • Oxcarbazepine – Stevens-Johnson syndrome, hyponatremia, low white blood cells, rash, weight gain, nausea, vomiting, dizziness, drowsiness, double vision, fatigue
  • Gabapentin and Pregabalin – dizziness, fatigue, sleepiness, weight gain
  • Vigabatrin – permanent peripheral vision loss, depression, dizziness, fatigue
  • Tiagabine – nonconvulsive status epilepticus, stomachache, thinking problems, anxiety, tremor
  • Zonizamide – aplastic anemia, kidney stones, Stevens-Johnson syndrome, decreased sweating leading to heat shock at high air temperatures, altered thinking, dizziness, sleepiness
  • Ethosuximide – blood abnormalities, multiple individual hypersensitivities, nausea, loss of appetite, drowsiness
  • Rufinamide – status epilepticus and aggravated seizures, vomiting, loss of appetite, fatigue, sleepiness
  • Lacosamide – nausea, headache, dizziness, double vision
  • Perampanel – severe mood change – homicidal ideation, anger, aggression, irritability, falls, dizziness, sleepiness
  • Ezogabine – urine retention, confusion, fatigue, dizziness, vertigo, tremor, lack of balance
  • Phenobarbital – blood abnormalities, depression, sleepiness, hyperactivity in children
  • Phenynoin – aplastic anemia, lupus-like syndrome, liver toxicity, acne, gum hyperplasia, hirsutism, double vision, dizziness, tremor, sleepiness
  • Felbamate – aplastic anemia, liver failure, weight loss, nausea, headache, dizziness
How Long is Epilepsy Treatment?
There is no one-fit-all answer to this question. Structural epilepsies often persist, unless surgically cured. Some genetic epilepsy syndromes are age locked, others are lifelong.

There are no universal recommendations regarding the length of treatment.

Long lasting remissions are not unusual even in genetic forms of epilepsy. So, lack of seizures, even without treatment, does not mean much long-term. Some epilepsies tend to moderate in over years, while others get worse.