The medications used to treat patients with epilepsy are called anticonvulsants. Many of these drugs are available and each has a different mechanism of action, but all serve to reduce the frequency of epileptic seizures. These medications can be given for long periods of time.
Treatment options are evaluated initially based on seizure subtype, as certain anticonvulsants may be indicated for treating some forms of epilepsy and contraindicated for others. When making decisions about treatment with a particular agent, the physician should always take into account the patient’s entire medical and medication histories, age and gender, and side-effect profile. It is important to evaluate the risks and benefits of treatment for each individual. That said, some general principles apply to treatment.
Monotherapy, treatment with a single agent, is the goal. Seizures can be controlled with one agent in approximately 75% of patients. Management becomes complicated when patients are given medications in combinations. This also risks increasing the number and frequency of side effects, making it less likely that patients will take their medication appropriately.
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.
Divided doses may be preferable with some medications, ensuring a more constant level of medication in the bloodstream.
Appropriate dosing levels depend on many factors, including the patient’s body weight, concomitant medications, and reaction to treatment.
Many neurologists believe brand-name medications are preferable to generic products. Generic medications may be produced by different companies without rigorous standards regarding adequate drug level at a particular dose. Patients who use these medications may therefore be exposed to fluctuating levels of medication. For some people with epilepsy, this can result in loss of seizure control. Brand-name anticonvulsants, meeting stringent standards, provide more confidence in the dose-blood level relationship.
Any medication can cause an allergic reaction. Dermatological problems, including “, are not uncommon. Life-threatening reactions, such as the Stevens-Johnson syndrome, can occur. It is essential that patients report any suspected reactions to their physician.
When medications are to be discontinued, it is almost always recommended that they be slowly tapered down in dosage strength because abrupt withdrawal can produce seizures.
Kidney and liver function testing should be performed to evaluate the ability of these organs to metabolize the medication; some drugs will require changing the dosage if function is impaired.
There is still some controversy over whether to treat a patient who has had only a single seizure. Approximately 75% of seizure sufferers have only one seizure and no reoccurrence. In making treatment decisions, it is helpful to look at risk factors that may predict a second seizure. These include lesions of the brain, an abnormal EEG, or a family history of seizure disorders.
Anticonvulsants can reduce the risk of further seizure activity. People who have had more than one seizure should probably be treated with anticonvulsants.
It is convenient to divide some of the existing medications into first-generation anticonvulsantsВ—older medicationsВ—and second-generationВ—more recently developedВ—drugs. Pharmaceutical research of new drugs is ongoing, with exciting developments in progress. The following medications are commonly prescribed for epilepsy.
Phenytoin (DilantinВ®) was first used in the late 1930s. It has become one of the more commonly used agents and often is considered the first-line drug to treat seizures. It is thought to work by suppressing electrical activity in brain nerve cells. It can be given orally or intravenously (IV), and a newer form of the drug, fosphenytoin (CerebryxВ®) can be injected into muscle. The oral form has the benefit of once-a-day dosing.
Phenytoin is a first-line agent for treating partial and generalized tonic-clonic (grand mal) seizures. It is also one of the main agents used with patients who present with status epilepticus. Phenytoin drug levels need to be monitored with laboratory testing. The therapeutic concentration recommended is between 10-20mg/L. 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 its use include gingival hyperplasia (overgrowth of the gums), hirsuitism/hypertrichosis (excessive hair growth), imbalance, lethargy, anemia, and, in long-term use, peripheral neuropathy (weakness).
Carbamazepine (TegretolВ®/CarbatrolВ®) has been in use for over 30 years. It is commonly prescribed for the treatment of partial and generalized tonic-clonic (grand mal) seizures. The mechanism by which it works is not well understood. In oral form, it can be taken 2 to 3 times a day; a recent development of the drug in sustained-release form allows for twice-a-day dosing.
Carbamazepine levels need to be followed with laboratory testing. The recommended therapeutic level is between 8-12mg/L. Liver function tests and CBC also need to be 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.
Recognized side effects include drowsiness, imbalance, nausea, anemia, and neutropenia (low, white blood cell count). Carbamazepine is also used to treat trigeminal neuralgia, or tic douloureux, a painful nerve disorder of the face, and other neuropathic pain syndromes.
Phenobarbital is the oldest of this group of anticonvulsants. It can be used to treat both partial and generalized seizures. It also is used as part of the protocol after phenytoin use in status epilepticus as well as in neonatal epilepsy. It is available in oral and intravenous forms.
Levels need to be monitored. The recommended therapeutic level is 15-40mg/L. A complete blood analysis also should be routinely conducted. 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.
Valproate (DepakoteВ®) has been in use for more than 20 years. It can be prescribed for a broad spectrum of anticonvulsant needs, including partial seizures, generalized tonic-clonic (grand mal) seizures, absence (petit mal), and myoclonic epilepsy. Its mechanism of action is thought to be related to the effect of a brain substance known as GABA (gamma-aminobutyric acid). It is available in oral form and must be taken 2 to 3 times per day for adequate dosing.
Drug levels must be monitored, as well as liver function, and blood count. The drug’s suggested therapeutic window is 50-100mg/L. Side effects include hepatotoxicity (liver damage), nausea, weight gain, allopecia (hair loss), and tremor.
Topiramate (TopamaxВ®) is used with other anticonvulsant drugs in the treatment of partial seizures and generalized tonic-clonic seizures in adults and children aged 2 to 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), a neurotransmitter that inhibits excitation of nerve cells in the brain. It is available in oral form, including sprinkles for children, and should be taken twice daily.
Major side effects include drowsiness, nausea, dizziness, and coordination problems. Children may have difficulty concentrating and may become agressive. Acute glaucoma and visual abnormality, a potentially very serious complication, has been reported in a small number of patients. If any abnormal visual symptoms occur, patients should notify their physician immediately. There are few drug interactions between TopamaxВ® and other medications or other anticonvulsants.
Gabapentin (NeurontinВ®) is indicated for the adjunctive treatment of partial seizures, with or without secondary generalization. Although it is structurally related to the substance GABA (gamma-aminobutyric acid), it does not interact with GABA receptors in the brain, and its mechanism of action is unknown. It is available in oral form and should be taken three times daily.
No laboratory monitoring of liver, kidney, or hematologic (blood) function is necessary with NeurontinВ®. Its major side effects are fatigue, dizziness, and imbalance. NeurontinВ® also has been used successfully in patients with neuropathic
Lamotrigine (LamictalВ®) is used for the adjunctive treatment of partial seizures. Its precise mechanism of action is unknown. It is presently available in oral form. LamictalВ® should be taken twice daily. No laboratory monitoring of Lamictal levels are necessary. Its major side effect is the appearance of a potentially life-threatening skin rash, particularly for patients who also are taking valproate (DepakoteВ®). Any patient taking Lamictal who develops a rash should immediately report it to his or her physician. Other side effects include headache, nausea, and dizziness.
Tiagabine (GabitrilВ®) is indicated for adjunctive therapy in adults with partial seizures. Its mechanism of action may be related to its effect on the brain substance GABA (gamma-aminobutyric acid). It is available in oral
form and should be given in divided doses two to four times daily. No laboratory monitoring of Gabitril levels are necessary. Some interaction likely exists when Gabitril is taken with other anticonvulsants, in that its metabolism may be altered. Side effects include dizziness and somnolence.
KeppraВ® (levetiracetam) Keppra is approved for use in adults as adjunctive therapy for the treatment of partial seizure disorders. The side effects can include fatigue, imbalance and behavioral changes, which often dissipate after the first month of treatment.
TrileptalВ® (oxcarbazepine) is indicated for monotherapy (used alone) in adults who have partial seizures and can be used in children as add-on therapy for partial seizures. The most common side effects include dizziness, sleepiness, nausea, and imbalance, but these do not warrant clinical observation.
Zonegram (Zonisamide) is approved for use in adults as adjunctive therapy for partial seizures. It has however, 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 drugs should not use Zonisamide since it is a derivative of this class of drug
Surgical resection of epileptogenic areas of the brain in patients with partial seizures sometimes is considered when seizure activity fails to respond to even the most aggressive medical management. Patients considered for these procedures are those with intractable seizures, even when given high levels of anticonvulsant drugs. Video-EEG monitoring on a long-term basis is used to determine where in the brain the seizures occur.
In some patients, placing electrodes beneath the scalp may help to define epileptogenic areas of the brain. Specialized centers throughout the country have multidisciplinary teams to aid in the evaluation of potential candidates for these procedures.
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