Anticonvulsant, or antiepileptic, medications are the treatment of choice for epilepsy and seizure disorders. Treatment options with anticonvulsants are evaluated initially based on seizure subtype, as certain anticonvulsants may be used for treating some forms of epilepsy. When making decisions about treatment with a particular agent, the doctor will take into account the patient's entire medical and medication histories, age, and gender as well as the side-effect profile of the medicine. Anticonvulsants are generally given life-long.
Treatment with one anticonvulsant drug, called monotherapy, is the goal. Seizures can be controlled with one agent in approximately 75% of individuals with epilepsy. It is very important for individuals with epilepsy and seizure disorders to take their medications as prescribed. For medications to work effectively, a relatively constant level of medication must be maintained in the body. This is accomplished by taking medication regularly as directed, without missing doses. The consequences of missed doses may be a single seizure, more devastating multiple seizures, or status epilepticus.
Phenytoin: Phenytoin (Dilantin®) has been used as an anticonvulsant medication for seizures since the late 1930s. Phenytoin is thought to suppress electrical activity in brain nerve cells, helping to control seizures. It can be given orally or intravenously (IV) and a newer form of the drug, fosphenytoin (Cerebryx®), can be injected into muscle.
Phenytoin is used in treating partial and generalized tonic-clonic (grand mal) seizures. Phenytoin is used with individuals with status epilepticus, although benzodiazepine drugs, such as diazepam (Valium®), are the drugs of choice for this condition. Phenytoin drug levels are monitored closely with laboratory testing, as altered levels of phenytoin may cause side effects such as lethargy and weakness. In addition, liver function testing and a complete blood count (CBC) need to be followed. Phenytoin has many interactions with other medications, and its own level can fluctuate when other drugs are taken.
Some of the side effects associated with phenytoin use include gingival hyperplasia (overgrowth of the gums), hirsuitism/hypertrichosis (excessive hair growth), imbalance, lethargy, anemia, and, in long-term use, peripheral neuropathy (nerve damage causing weakness).
Carbamazepine: Carbamazepine (Tegretol® or Carbatrol®) is commonly prescribed for the treatment of partial and generalized tonic-clonic (grand mal) seizures. Carbamazepine levels are followed closely with laboratory testing. Liver function tests and complete blood count (CBC) are also checked routinely. Carbamazepine can affect the levels of a number of other drugs in the body, and its own level can fluctuate when other agents are taken.
Side effects include drowsiness, imbalance, nausea, anemia, neutropenia (a low white blood cell count), and agranulocytosis (a lack of white blood cells).
Phenobarbital: Phenobarbital is a barbiturate medication that is used to treat both partial and generalized seizures. Phenobarital, or phenobarb, is available in oral and intravenous forms. Blood levels are monitored closely. A complete blood analysis and liver function tests are also routinely monitored. Phenobarbital can cause changes in the metabolism of other drugs through its actions on liver enzymes. Side effects may include drowsiness, cognitive impairment, and irritability.
Valproic acid: Valproic acid (Depakene®, Depakote®) is used for partial seizures, generalized tonic-clonic (grand mal) seizures, absence (petit mal), and myoclonic epilepsy. Valproic acid seems to affect the brain with a neurotransmitter known as GABA (gamma-aminobutyric acid). GABA inhibits the excitation of nerve cells in the brain. Drug levels are monitored closely. A complete blood analysis and liver function tests are also routinely monitored. Side effects include hepatotoxicity (liver damage), nausea, weight gain, alopecia (hair loss), and tremor.
Topiramate: Tomipramate (Topamax®) is used with other anticonvulsant drugs in the treatment of partial seizures and generalized tonic-clonic seizures in adults and children aged 2-16. Although its precise mechanism of action is unknown, one theory suggests that its anticonvulsant activity may be due in part to increasing GABA (gamma-aminobutyric acid). Side effects include drowsiness, nausea, dizziness, and coordination problems. Children may have difficulty concentrating and may become aggressive.
Gabapentin: Gabapentin (Neurontin®) is indicated for the treatment of partial seizures, with or without secondary generalization. The precise mechanism of action is unknown. No laboratory monitoring of liver, kidney, or hematologic (blood) function is usually necessary with gabapentin. The major side effects are drowsiness, fatigue, dizziness, and imbalance. Gabapentin has also been used successfully in individuals with neuropathic pain syndromes. When an individual begins therapy with gabapentin, it is recommended by healthcare professionals to use caution when driving or operating heavy machinery until drowsiness and fatigue subsides, which make take 2-4 weeks.
Lamotrigine: Lamotrigine (Lamictal®) is used in the treatment of partial seizures. The precise mechanism of action is unknown. No laboratory monitoring of lamotrigine levels are usually necessary. The major side effect is the appearance of a potentially life-threatening skin rash (called Stevens-Johnson syndrome), particularly for patients who also are taking valproic acid (Depakote®). Any individuals taking lamotrigine who develops a rash should immediately report it to a doctor. Other side effects include headache, nausea, and dizziness.
Tiagabine: Tiagabine (Gabitril®) is used in adults with partial seizures. Its mechanism of action may be related to its effect on GABA (gamma-aminobutyric acid). No laboratory monitoring of tiagabine levels are usually necessary. Some interaction likely exists when tiagabine is taken with other anticonvulsants, in that its metabolism may be altered. Side effects include dizziness and somnolence.
Levetiracetam: Levetiracetam (Keppra®) is used in adults along with other anticonvulsants as treatment for partial seizure disorders. The side effects can include fatigue, imbalance, and behavioral changes, which often dissipate after the first month of treatment.
Oxacarbazine: Oxcarbazepine (Trileptal®) is used alone in adults who have partial seizures and can be used in children for partial seizures. Oxacarbazine is usually taken with other anticonvulsant medications for seizure control. The most common side effects include dizziness, sleepiness, nausea, and imbalance.
Zonisamide: Zonisamide (Zonegram®) is approved for use in adults as adjunctive therapy for partial seizures. It has been used fairly extensively in other countries for use in other seizure types including generalized seizures, myoclonic seizures, and absence seizures. Side effects can include dizziness, imbalance, and fatigue. Individuals who are allergic to sulfonamide (sulfa) drugs should not use zonisamide.
Benzodiazepines belong to the group of medicines called central nervous system (CNS) depressants (medicines that slow down the nervous system). Most benzodiazepines are used to relieve anxiety and insomnia (lack of sleep). Clonazepam (Klonopin®), clorazepate (Tranxene®), diazepam (Valium®), and lorazepam (Ativan®) are used in the treatment of status epilepticus. Benzodiazepines may cause drowsiness and sedation. Benzodiazepines also have the potential for abuse and may cause physical addiction.
Other conventional treatments
Ketogenic diet: A ketogenic diet is a diet high in fat content and is usually reserved for epilepsy patients that have tried two anti-convulsant medications without relief from seizures. Ketogenic diets seem to alter brain function and decrease seizure activity.
The goal of the diet is to get the body to produce ketones, which cause the body to use fat instead of glucose for energy. Ketone bodies are compounds that are produced as by-products when fatty acids are broken down for energy.
If carbohydrates (which are composed of sugars) are eliminated from the diet, and a diet very high in fat is substituted, the body has no dietary sources of glucose. In the event of low blood glucose, most other tissues have additional energy sources besides ketone bodies (such as fatty acids) but the brain does not. After the diet has been changed to lower blood glucose for three days, the brain gets 30% of its energy from ketone bodies. After four days, this goes up to 70%.
As a result, ketones are made from the available sources and these are used as fuel instead. Even a very small amount of sugar can cause the body to shift to glucose production and use, which it prefers to ketones. For example, this restriction is such that children on the diet have to be careful to take sugarless daily multivitamins. Some children with epilepsy have been helped by adopting a rigid diet that is high in fat and protein and low in carbohydrates.
Elevated levels of ketones in the body of individuals with epilepsy may be associated with seizure control and seizure freedom.
Surgery: Surgical removal of areas of the brain where partial seizures are occurring is used when seizure activity fails to respond to even the most aggressive medical anticonvulsant therapies. Patients considered for these procedures are those with intractable seizures, even when given high levels of anticonvulsant drugs. During the procedure, the surgeon makes an incision in the scalp and removes a piece of the skull bone. The area(s) responsible for seizure activity are then removed. Some individuals will be able to reduce the medications after the surgery. In some cases, surgery for epilepsy can cause complications such as permanently altering cognitive abilities. It is important to discuss all options with a doctor.
Vagus nerve stimulation: The vagus nerve is a cranial nerve controlling muscles involved with swallowing, speaking, and coughing. The nerve is also involved with receiving input from and sending information about the heart, stomach, and lungs to the brain. A device called a vagus nerve stimulator is implanted into the chest under the collarbone. Wires from the stimulator are wrapped around the vagus nerve in the neck. The device turns on and off according to an adjustable program. The device has been reported to reduce seizures by about 20-40%. Most individuals still need to take anticonvulsant medication, but a reduction in dosage is possible.
Good scientific evidence
Yoga: Yoga is an ancient system of relaxation, exercise, and healing with origins in Indian philosophy. Several human studies report a reduction in the number of monthly seizures with the use of Sahaja yoga, when it is added to standard anti-seizure drug treatment, or a yoga meditation protocol. This research is preliminary, and better studies are needed.
Unclear or conflicting scientific evidence
Atkins Diet®: The Atkins Diet® proposes that, in order to lose weight, one should adopt an eating style that radically departs from the U.S. Food and Drug Administration's (FDA) food pyramid. It proposes the elimination of most carbohydrates as a source of energy; in the place of carbohydrates, the diet advocates the significantly increased consumption of fats, including trans fats and hydrogenated oils. The high protein diet has been used traditionally by individuals with epilepsy. The efficacy of the Atkins Diet® in individuals with epilepsy has been investigated in two open label studies. Preliminary evidence suggests that seizure frequency may be reduced in some patients. Well designed controlled studies are needed. Patients should consult a qualified healthcare professional before beginning any new diet or adjusting their current regimen.
Bacopa: Bacopa (Bacopa monnieri) is a traditional herb used in Indian or Ayurvedic medicine. Although bacopa is traditionally used in Ayurvedic medicine for epilepsy, high-quality clinical trials are lacking. One methodologically weak study found some evidence that bacopa reduces seizure frequency. However, more research is needed before using bacopa in epilepsy and seizure disorders.
Caprylic acid: Caprylic acid is an eight-carbon fatty acid naturally found in palm and coconut oil and in the milk of humans and cows. Some forms of epilepsy respond to diets that are high in fat and low in carbohydrates. Currently, the effects of caprylic acid alone to treat epilepsy in children are not well studied. Additional study is needed in this area.
Chiropractic: Chiropractic is a healthcare discipline that focuses on the relationship between musculoskeletal structure (primarily the spine) and body function (as coordinated by the nervous system), and how this relationship affects the preservation and restoration of health. Chiropractic manipulation may help decrease pressure on nerves that may be causing seizure activity.
Euphorbia: Euphorbia alkaloid, which is the active ingredient in Euphorbia fisheriana, may have anticonvulsant effects. Thus, this alkaloid might be useful in patients with epilepsy. Additional study is needed in this area.
Meditation: Various forms of meditation have been practiced for thousands of years throughout the world, with many techniques originating in Eastern religious practices. In modern times, numerous meditation types are in use, often outside of their original religious and cultural contexts. Yoga meditation may help prevent seizures in epileptics, although higher quality clinical studies are needed.
Melatonin: Melatonin is a neuro-hormone produced in the brain by the pineal gland from the amino acid tryptophan. The synthesis and release of melatonin are stimulated by darkness and suppressed by light, suggesting the involvement of melatonin in circadian rhythm and regulation of diverse body functions. Levels of melatonin in the blood are highest prior to bedtime. The role of melatonin in seizure disorder is controversial. There are several reported cases of children with intractable seizures or neurological damage who improved with regular nighttime melatonin administration. Limited animal research also suggests possible anti-seizure effects. However, there has also been a report that melatonin may actually lower seizure threshold and increase the risk of seizures. Better evidence is needed in this area before a clear conclusion can be drawn regarding the safety or effectiveness of melatonin in seizure disorder.
Taurine: Taurine is a nonessential amino acid-like compound. Taurine is found in high abundance in the tissues of many animals, especially sea animals, and in much lower concentrations in plants, fungi, and some bacteria. Taurine is important in several metabolic processes of the body, including stabilizing cell membranes in electrically active tissues, such as the brain and heart. In animal studies, taurine has been suggested to have an antiepileptic action. The effect of taurine on seizures in humans has been investigated several clinical studies. Taurine may be beneficial in these patients. However, well-designed, randomized clinical trials need to be conducted.
Vitamin D: Vitamin D is found in numerous dietary sources such as fish, eggs, fortified milk, and cod liver oil. The sun is also a significant contributor to our daily production of vitamin D and as little as 10 minutes of exposure is thought to be enough to prevent deficiencies. Supplementation with vitamin D has been reported to reduce seizure frequency in initial research. Further study is needed to confirm these results.
Vitamin E: Vitamin E is a fat-soluble vitamin with antioxidant properties. Vitamin E has been evaluated as an addition to other drugs used to prevent seizures, particularly in refractory epilepsy. The evidence is not conclusive.
Fair negative scientific evidence
5-HTP: 5-HTP, or 5-hydroxytryptophan, is the precursor of the neurotransmitter serotonin. It is obtained commercially from the seeds of the plant Griffonia simplicifolia. 5-HTP has been studied as a treatment for various myoclonic syndromes and epilepsy, but available research does not support the use of 5-HTP for these conditions at this time.
Traditional or theoretical uses which lack sufficient evidence
Integrative therapies traditionally used in seizure disorders, but that lack sufficient scientific evidence include: abuta (Cissampelos pareira), homeopathic aconite (Aconitum napellus), acupressure (Shiatsu), African wild potato (Hypoxis hemerocallidea), aromatherapy, bitter orange (Citrus aurantium), black currant (Ribes nigrum), blue cohosh (Caulophyllum thalictroides),choline, creatine, ginseng (Panax ginseng), kava kava (Piper methysticum), massage, music therapy, niacin (Vitamin B3, Nicotinic acid), passion flower (Passiflora incarnata), reishi mushroom (Ganoderma lucidum), resveratrol, SAMe, valerian (Valeriana officinalis), and zinc.