What are antiepileptic drugs?
Antiepileptic drugs aim to rebalance the chemo-electric activity in the brain, the dysfunction of which causes seizures.
Antiepileptic drugs (AED) are medications given to control epileptic seizures and convulsions. Antiepileptic drugs do not cure epilepsy, but may reduce the frequency, duration, and severity of seizures. Most people must continue taking antiepileptic drugs for their entire lives.
Seizures may also be caused by high fevers and psychological distress. Antiepileptic drugs are prescribed only for seizures from epilepsy and not for other kinds of seizures.
What is epilepsy?
Epilepsy is a disorder that causes abnormal electrical activity in the brain’s nerve cells (neurons), resulting in recurrent, unprovoked seizures. Epilepsy is a spectrum disorder and may happen in people of any age, though it is more common in young children.
Epileptic seizures may be generalized, affecting the whole brain, or partial, localized to one part of the brain. Localized epileptic seizures may or may not spread to other parts of the brain.
A seizure is a sudden burst of abnormal electrical activity in the brain, which may induce abnormal behavior and uncontrolled muscle movements in a person. A seizure may or may not be accompanied by convulsions.
What is the best antiepileptic drug?
There is no single best antiepileptic drug, and the choice of antiepileptic drug depends on factors such as:
- The type of epilepsy
- The age of the patient
- Chance of pregnancy
- Toleration of side effects
- Other coexisting conditions
- Lifestyle habits, such as alcohol consumption
Antiepileptic drugs may be of two kinds:
- Narrow spectrum AEDs: Designed for specific types of seizures such as
- Partial
- Focal
- Absence
- Myoclonic
- Broad spectrum AEDs: Treat patients who have more than one type of seizures.
A patient may respond to a single antiepileptic drug (monotherapy), or may require a combination of drugs, depending on the type of epilepsy. Antiepileptic drug regimens are usually started using just one medication in a low dosage. The dosage is increased slowly to reach the maximum therapeutic effect with the fewest side effects.
How do antiepileptic drugs work?
Different classes of antiepileptic drugs use different mechanisms to prevent a seizure, some of which are not clearly understood. Some of the primary ways antiepileptic drugs work are:
- Sodium channel blockers alter the electrical state of the neuron by blocking the sodium ion channels, to prevent them from firing electrical signals.
- Calcium channel blockers stop the transmission of electrical signals between neurons by calcium ion channels, by blocking the release of chemicals which transmit the signals (neurotransmitters).
- GABA (Gamma-aminobutyric acid) enhancers: GABA is the brain’s natural neurotransmitter that stops transmission of electrical signals. GABA enhancers work by
- Increasing GABA production
- Reducing GABA metabolic breakdown
- Increasing the transmission of GABA between neurons
- Glutamate blockers block the action of glutamate, a neurotransmitter that promotes the brain’s electrical activity by facilitating the flow of sodium, calcium, and potassium ions through a neuron. Much like a battery has a positive and negative charge, this ion balance maintains the electrical polarity of the nerve cell.
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What are the side effects of antiepileptic drugs?
The first-generation antiepileptic drugs can have severe side effects and are known to cause liver damage. People taking these AEDs require regular blood tests to monitor kidney and liver functions. Some antiepileptic drugs may also adversely interact with other drugs.
Though side effects cannot be eliminated, newer drugs have been developed with:
- Better efficacy
- Fewer side effects
- Less toxicity
If given during pregnancy, many of the antiepileptic drugs can cause birth defects in the child, such as:
- Cleft palate
- Cleft lip
- Congenital heart disease
- Slowed growth rate
- Mental deficiency
Some of the common antiepileptic drugs and their main possible side effects are listed below.
Brivaracetam (Briviact)
Adjunct or monotherapy for partial-onset seizures.
Side effects include:
Cannabidiol (Epidiolex)
For seizures associated with Lennox-Gastaut syndrome or Dravet syndrome.
Side effects include:
- Lethargy,
- sleepiness,
- fatigue,
- increased appetite,
- diarrhea, and
- sleep disorders.
Carbamazepine (Carbatrol or Tegretol)
For partial, and generalized tonic-clonic seizures.
Side effects include:
Cenobamate (Xcopri)
Adjunct therapy to reduce seizure frequency.
Side effects include:
- Insomnia,
- dizziness,
- fatigue,
- double vision (diplopia), and
- headache.
Clobazam (Onfi)
For partial and generalized epilepsy and as intermittent and preventive treatment.
Side effects include:
- Dizziness,
- lack of muscle coordination (ataxia),
- blurred vision,
- diplopia,
- irritability,
- depression,
- muscle fatigue and
- weakness.
Clonazepam (Klonopin)
For myoclonic seizures and emergency treatment.
Side effects include:
- Ataxia,
- loss of appetite,
- restlessness,
- depression,
- cardiovascular or respiratory depression.
Children may have hyperactivity and drooling.
Diazepam (Valium)
For short-term treatment of frequent, acute repetitive seizures.
Side effects include:
- Ataxia,
- loss of appetite,
- restlessness,
- depression,
- cardiovascular or respiratory depression.
Children may have hyperactivity and drooling.
Eslicarbazepine (Aptiom)
For partial-onset seizures.
Side effects include:
Ethosuximide (Zarontin)
Treatment for absence seizures.
Side effects include:
- Nausea,
- vomiting,
- decreased appetite, and
- weight loss.
Ezogabine (Potiga)
Adjunct therapy for uncontrolled partial-onset seizures.
Side effects include:
- Drowsiness,
- dizziness,
- memory problems,
- fatigue,
- weakness, and
- trouble concentrating.
Felbamate (Felbatol)
Restricted to treatment of severe uncontrolled partial epilepsy or Lennox-Gastaut syndrome, because of potentially fatal toxic side effects.
Side effects include:
- Decreased appetite,
- weight loss,
- insomnia,
- headache,
- depression, and
- rarely bone marrow or liver failure.
Fosphenytoin (Cerebyx)
For short term administration via injection or IV.
Side effects include:
- Nausea,
- vomiting,
- headache,
- dizziness,
- fatigue,
- slurred speech,
- acne,
- rash,
- increased hair growth,
- involuntary eye movements (nystagmus), and
- osteoporosis if taken over a long time.
Gabapentin (Neurontin)
For partial and secondary generalized tonic-clonic seizures.
Side effects include:
- Drowsiness,
- dizziness,
- ataxia,
- nystagmus,
- headache,
- tremor,
- fatigue,
- diplopia,
- rhinitis,
- nausea, and
- vomiting.
Lacosamide (Vimpat)
Adjunct and monotherapy for partial onset seizures in adults and adolescents over 17 years old.
Side effects include:
- Dizziness,
- fatigue,
- nausea, and
- diplopia.
Lamotrigine (Lamictal)
Inhibits release of glutamate and used as an adjunct therapy for partial onset and secondary generalized tonic-clonic seizures, transition to monotherapy and Lennox-Gastaut syndrome. Used during pregnancy because of fewer side effects.
Side effects include:
- Dizziness,
- insomnia,
- headache,
- ataxia,
- diplopia,
- tremor,
- hypersensitivity and,
- potentially fatal Stevens-Johnson rash in children.
Levetiracetam (Keppra)
Adjunct treatment for primary generalized tonic-clonic seizures, partial onset seizures, and myoclonic seizures.
Side effects include:
- Weakness,
- drowsiness,
- dizziness,
- headache,
- convulsion,
- infection,
- pharyngitis,
- flu-like symptoms.
Midazolam (Nayzilam)
For short-term treatment of frequent, acute, repetitive seizures.
Side effects include:
- Drowsiness,
- dizziness headache,
- nose pain,
- runny nose and
- throat irritation.
Oxcarbazepine (Oxtellar XR, Trileptal)
For partial seizures.
Side effects include:
- Sleepiness,
- headache,
- dizziness,
- rash,
- weight gain,
- gastrointestinal problems,
- fatigue,
- ataxia, and
- hair loss (alopecia).
Perampanel (Fycompa)
For partial onset seizures and primary generalized tonic-clonic seizures in 12 years and older patients.
Side effects include:
- Aggression,
- hostility,
- irritability,
- anger,
- paranoia,
- euphoric mood,
- agitation, and
- mood swings.
Phenobarbital
Low-cost broad-spectrum drug effective for many types of seizures and first-line treatment for continuous seizures (status epilepticus).
Side effects include:
- Cognitive and behavior changes,
- sleepiness,
- poor concentration,
- irritability,
- ataxia, and
- decreased libido.
Long-term use may cause vitamin D and folate deficiency.
Phenytoin (Dilantin)
For partial and secondary generalized seizures, controls spread of seizures.
Side effects include:
- Nausea,
- vomiting,
- headache,
- dizziness,
- fatigue,
- slurred speech,
- acne,
- rash,
- vitamin K and folate deficiency,
- loss of libido,
- hormonal dysfunction,
- bone marrow hyperplasia and osteoporosis if taken over a long time
Pregabalin (Lyrica)
Adjunct therapy for partial-onset seizures in adults and children over one month old.
Side effects include:
- Dizziness,
- drowsiness,
- dry mouth,
- peripheral edema,
- blurred vision,
- weight gain and
- difficulty concentrating.
Primidone (Mysoline)
For partial onset and secondary generalized seizures.
Side effects include:
- Sleepiness,
- dizziness,
- nausea,
- cognitive and
- behavior changes.
Rufinamide (Banzel)
Adjunct therapy for Lennox-Gastaut syndrome.
Side effects include:
- Drowsiness,
- dizziness,
- lack of coordination,
- trouble walking,
- fatigue,
- headache,
- nausea,
- vomiting,
- loss of appetite, and
- double/blurred vision.
Stiripentol (Diacomit)
Adjunct therapy for Dravet syndrome.
Side effects include:
- Sleepiness,
- loss of appetite,
- weight loss,
- ataxia,
- agitation,
- nausea,
- tremor,
- low muscle tone, and
- speech difficulties.
Tiagabine (Gabitril)
Adjunct treatment for refractory partial seizures.
Side effects include:
- Dizziness,
- sleepiness,
- fatigue,
- weakness,
- irritability,
- anxiety,
- depression,
- mood swings,
- psychosis,
- confusion,
- tremor,
- diarrhea,
- abdominal pain,
- headache,
- ataxia,
- pharyngitis, and
- rash.
Topiramate (Topamax)
For partial onset and secondary generalized tonic-clonic seizures, primary generalized tonic-clonic seizures, and Lennox-Gastaut syndrome.
Side effects include:
- Ataxia,
- lack of concentration,
- confusion,
- dizziness,
- fatigue,
- tingling (paresthesia) in the extremities,
- sleepiness,
- memory problems,
- depression,
- agitation, and
- slowness of speech.
Valproate, valproic acid (Depakene, Depakote)
For primary generalized seizures, photosensitive epilepsy, Lennox-Gastaut syndrome and partial seizures. Not to be used if pregnant.
Side effects include:
- Dizziness,
- nausea,
- vomiting,
- tremor,
- hair loss,
- weight gain,
- depression in adults,
- irritability in children and slowness in thinking.
Long-term use can cause bone thinning, ankle swelling and menstrual irregularity.
Hearing loss, liver damage, pancreatitis and low platelet counts are more dangerous but rare side effects.
Vigabatrin (Sabril, Vigadrone)
Adjunct therapy for adults and children over 2 years with refractory complex partial seizures and monotherapy for infantile spasms in children under 2 years of age.
Side effects include:
- Drowsiness,
- dizziness,
- difficulty concentrating,
- nausea,
- vomiting,
- diarrhea,
- headache,
- fatigue,
- weight gain, and
- vision loss.
Zonisamide (Zonegran)
Adjunct therapy for partial seizures in patients who are over 12 years old.
Side effects include:
- Dizziness,
- drowsiness,
- fatigue,
- anorexia,
- headache,
- ataxia,
- speech abnormalities,
- irritability,
- mental slowing,
- weight gain,
- kidney stones and
- Stevens-Johnson rash.