Anti-epileptic drugs (AEDs) include many types of medications but all act as anticonvulsants. Many newer AEDs are better tolerated than the older, standard AEDs, although they can still have troublesome side effects. Newer AEDs often cause less sedation and require less monitoring than older drugs. Although newer AEDs are generally FDA-approved for use as add-ons to standard drugs that have failed to control seizures, they are often prescribed as single drugs. Specific choices usually depend on the patient’s particular condition and the specific side effects of the AED.
All antiepileptic drugs can increase the risks of suicidal thoughts and behavior (suicidality). Research has shown that the highest risk of suicide can occur as soon as 1 week after beginning drug treatment and can continue for at least 24 weeks. Patients who take these drugs should be monitored for signs of depression, changes in behavior, or suicidality.
There are dozens of anti-epileptic drugs. The following are some of the most commonly prescribed.
Valproate sodium (Depacon, generic), valproic acid (Depakene, generic), and divalproex sodium (Depakote, generic) are anticonvulsants that are chemically very similar to each other. (In this report, they are collectively referred to as valproate.) Valproate products are the most widely prescribed anti-epileptic drugs worldwide. They are the first choice for patients with generalized seizures and are used to prevent nearly all other major seizures as well.
Side Effects. These drugs have a number of side effects that vary depending on dosage and duration. Most side effects occur early in therapy and then subside. The most common side effects are upset stomach and weight gain. Less common side effects include dizziness, hair thinning and loss, and difficulty concentrating.
Serious side effects include:
- A higher risk for serious birth defects than other AEDs especially if taken during the first trimester of pregnancy. In particular, these drugs are associated with facial cleft deformities (cleft lip or palate) and cognitive impairment. [See "Treatment During Pregnancy" in Treatment section.]
- Liver damage or failure is a rare but extremely dangerous side effect that usually affects children under 2 years of age who have birth defects and are taking more than one antiseizure drug.
- Pancreatitis (inflammation of the pancreas) and kidney problems are also rare but serious side effects.
Carbamazepine (Tegretol, Equetro, Carbatrol, and generic) is used for many types of epilepsy including partial seizures, generalized tonic-clonic (grand mal) seizures, and mixed seizures. A chewable form is available for children.
Side Effects. Common side effects of carbamazepine include dizziness, drowsiness, problems with walking and coordination, nausea, and vomiting.
Carbamazepine can make hormonal forms of birth control less effective. It can also interact with many types of prescription medication.
More serious side effects may include:
- Rare but life-threatening skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome. These skin reactions cause rash, mouth sores, peeling and blistering skin, and other severe symptoms. People of Asian ancestry have a 10 times greater risk for skin reactions than other ethnicities.
- Bone marrow blood disorders such as aplastic anemia and agranulocytosis.
- Patients should be sure to inform their doctors if they have any sign of sore throat, fever, easy bruising, or unusual bleeding, or severe fatigue,
- Long-term therapy may cause bone density loss (osteoporosis) in women.
- Birth defects can occur if taken during pregnancy. This drug may also be passed through breast milk.
Note: Grapefruit, Seville oranges, and tangelos can increase carbamazepine's blood levels and risk of adverse effects.
Phenytoin (Dilantin, generic) is often prescribed as a first-line drug to treat generalized tonic-clonic (grand mal) seizures and complex partial seizures. This drug may be used alone or in combination with other AEDs.
Side Effects. The most common side effects of phenytoin include problems with walking and coordination, slurred speech, confusion, dizziness, trouble sleeping, and tremor.
More serious side effects may include:
- Softening of the bones (osteomalacia), which can lead to fractures;
- Severe and rare life-threatening skin reactions (Stevens-Johnson syndrome, toxic epidermal necrosis)
- Birth defects if taken during pregnancy
- Drug interactions with other prescription medications
Barbiturates (Phenobarbital and Primidone)
Phenobarbital (Luminal, generic), also called phenobaritone, is a barbiturate anticonvulsant. Primidone (Mysoline, generic) is converted in the body to phenobarbital, and has the same benefits and adverse effects.
Barbiturates may be used to prevent grand mal (tonic-clonic) seizures or partial seizures. They are no longer typically used as first-line drugs, although they may be the initial drug prescribed for newborns and young children.
Side Effects. Phenobarbital has fewer toxic effects on other parts of the body than most anti-epileptic drugs, and drug dependence is rare, given the low doses used for treating epilepsy. Nevertheless, many patients experience difficulty with side effects.
Patients sometimes describe their state as "zombie-like." The most common and troublesome side effects are:
- Memory problems
- Problems with tasks requiring sustained performance
- Problems with motor skills
- Hyperactivity in some patients, particularly in children and the elderly
- Depression in some adults
When taken during pregnancy, phenobarbital, like phenytoin and valproate, may lead to impaired cognitive function in the child. There is some evidence that phenobarbitol may cause heart problems in the fetus.
Ethosuximide and Similar Drugs
Ethosuximide (Zarontin, generic) is used for petit mal (absence) seizures in children and adults when the patient has experienced no other type of seizures. Methsuximide (Celontin), a drug similar to ethosuximide, may be suitable as an add-on treatment for intractable epilepsy in children.
Side Effects. This drug can cause stomach problems, dizziness, loss of coordination, and lethargy. In rare cases, it may cause severe and even fatal blood abnormalities. Periodic blood counts are recommended for patients taking this drug.
Clonazepam (Klonopin, generic) is recommended for myoclonic and atonic seizures that cannot be controlled by other drugs and for Lennox-Gastaut epilepsy syndrome. Although clonazepam can prevent generalized or partial seizures, patients generally develop tolerance to the drug, which causes seizures to recur.
Side Effects. People who have had liver disease or acute angle glaucoma should not take clonazepam, and people with lung problems should use the drug with caution. Clonazepam can be addictive, and abrupt withdrawal may trigger status epilepticus. Side effects include drowsiness, imbalance and staggering, irritability, aggression, hyperactivity in children, weight gain, eye muscle problems, slurred speech, tremors, skin problems, and stomach problems.
Lamotrigine (Lamictal, generic) is approved as add-on (adjunctive) therapy for partial seizures, and generalized seizures associated with Lennox-Gastaut syndrome, in children aged 2 years and older and in adults. Lamotrigine is also approved as add-on therapy for treatment of primary generalized tonic-clonic (PGTC) seizures, also known as “grand mal” seizures, in children aged 2 years and older and adults. Lamotrigine can be used as a single drug treatment (monotherapy) for adults with partial seizures. Birth control pills lower blood levels of lamotrigine.
Side Effects. Common side effects include dizziness, headache, blurred or double vision, lack of coordination, sleepiness, nausea, vomiting, insomnia, and rash. Although most cases of rash are mild, in rare cases the rash can become very severe. The risk of rash increases if the drug is started at too high a dose or if the patient is also taking valproate. (Serious rash is more common in young children who take the drug than it is in adults.) Rash is most likely to develop within the first 8 weeks of treatment. Be sure to immediately notify your doctor if you develop a rash, even if it is mild.
Lamotrigine may cause aseptic meningitis. Symptoms of meningitis may include headache, fever, stiff neck, nausea, vomiting, rash, and sensitivity to light. Patients who take lamotrigine should immediately contact their doctors if they experience any of these symptoms.
Gabapentin (Neurontin, generic) is an add-on drug for controlling complex partial seizures and generalized partial seizures in both adults and children.
Side Effects. Side effects include sleepiness, headache, fatigue, and dizziness. Some weight gain may occur. Children may experience hyperactivity or aggressive behavior. Long-term adverse effects are still unknown.
Pregabalin (Lyrica) is similar to gabapentin. It is approved as add-on therapy to treat partial-onset seizures in adults with epilepsy.
Side Effects. Dizziness, sleepiness, dry mouth, swelling in hands and feet, blurred vision, weight gain, and trouble concentrating may occur.
Topiramate (Topamax, generic) is similar to phenytoin and carbamazepine and is used to treat a wide variety of seizures in adults and children. It is approved as add-on therapy for patients 2 years and older with generalized tonic-clonic seizures, partial-onset seizures, or seizures associated with Lennox-Gastaut syndrome. It is also approved as single drug therapy.
Side Effects. Most side effects are mild to moderate and can be reduced or prevented by beginning at low doses and increasing dosage gradually. Common side effects may include numbness and tingling, fatigue, abnormalities of taste, difficulty concentrating, and weight loss. Serious side effects may include acute glaucoma and other eye problems. Tell your doctor right away if you have blurred vision or eye pain. If used during pregnancy, topiramate may increase the risk for cleft lip or palate birth defects.
Oxcarbazepine (Trileptal, generic) is similar to phenytoin and carbamazepine but generally has fewer side effects. It is approved as single or add-on therapy for partial seizures in adults and for children ages 4 years and older.
Side Effects. Serious side effects, while rare, include Stevens-Johnson syndrome and toxic epidermal necrolysis. These skin reactions cause a severe rash that can be life threatening. Rash and fever may also be a sign of multi-organ hypersensitivity, another serious side effect associated with this drug. Oxcarbazepine can reduce sodium levels (hyponatremia). Your doctor may want to monitor the sodium (salt) level in your blood. This drug can reduce the effectiveness of birth control pills. Women who take oxcarbazepine may need to use a different type of contraceptive.
Zonisamide (Zonegran, generic) is approved as add-on therapy for adults with partial seizures.
Side Effects. Zonisamide increases the risk for kidney stones. It may reduce sweating and cause a sudden rise in body temperature, especially in hot weather. Other side effects tend to decrease over time and may include dizziness, forgetfulness, headache, weight loss, and nausea.
Levetiracetam (Keppra, generic) is approved both in oral and intravenous forms as add-on therapy for treating many types of seizures in both children and adults.
Side Effects. These tend to occur mostly in the first month. They include sleepiness, dizziness, and fatigue. More serious side effects may include muscle weakness and coordination difficulties, behavioral changes, and increased risk of infections.
Tiagabine (Gabitril) has properties similar to phenytoin and carbamazepine.
Side Effects. Tiagabine may cause significant side effects including dizziness, fatigue, agitation, and tremor. The FDA has warned that tiagabine may cause seizures in patients without epilepsy. Tiagabine is only approved for use with other anti-epilepsy medicines to treat partial seizures in adults and children 12 years and older
Ezogabine (Potiga), a potassium channel opener, was approved in 2011 for treatment of partial seizures in adults. Ezogabine is used as an add-on (adjunctive) medication. Its most serious side effect is urinary retention. Patients should be monitored for symptoms such as difficulty initiating urination, weak urine stream, or painful urination. Other side effects may include coordination problems, memory problems, fatigue, dizziness, and double vision. In 2013, the FDA warned that this drug may cause retina abnormalities, vision loss, and skin discoloration.
Perampanel (Fycompa) was approved in 2012 as add-on treatment for partial onset seizures in patients age 12 years and older. Perampanel is the first in a new class of AEDs for uncontrolled partial epilepsy. It targets the AMPA glutamate receptor, which is involved in seizure activity. Perampanel is taken as a once-daily tablet. Common side effects may include dizziness, drowsiness, and fatigue. Perampanel also has a boxed warning to alert about potential risks of serious mood changes and mental disturbances including irritability, aggression, anxiety, and violent thoughts or behaviors.
Less Commonly Used AEDs
Felbamate. Felbamate (Felbatol) is an effective antiseizure drug. However, due to reports of deaths from liver failure and from a serious blood condition known as aplastic anemia, felbamate is recommended only under certain circumstances. They include severe epilepsy, such as Lennox-Gastaut syndrome, or as monotherapy for partial seizures in adults when other drugs fail.
Vigabatrin. Vigabatrin (Sabril) has serious side effects, such as vision disturbances, and is generally prescribed only in specific cases. It is sometimes given in low doses for patients with Lennox-Gastaut syndrome. Vigabatrin is also prescribed as a low-dose oral solution to treat infantile spasms in children ages 1 month to 2 years.
Clobazam. Clobazam (Onfi) is a benzodiazepine drug prescribed as add-on treatment for children with Lennox-Gastaut syndrome. In 2013, the FDA warned that clobazam can cause rare but serious skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. The risk for these reactions is highest during the first 8 weeks of treatment. While these types of serious skin reactions can occur with other AEDs, they are not usually associated with benzodiazepine drugs.