Second-Generation Anticonvulsants

Second-Generation Anticonvulsants to Treat Epilepsy

Topiramate (Topamax®)—This drug 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. It also is approved to prevent migraine headaches. Its precise mechanism of action is unknown, but 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 is taken twice daily.

In March 2011, the U.S. Food and Drug Administration (FDA) released information indicating that topiramate increases the risk for birth defects such as cleft lip and cleft palate when taken during the first trimester of pregnancy. Prescribing information for this medication now includes a stronger warning about this risk but states that in some women with epilepsy, the potential benefits of the drug might outweigh the higher risk.

There are few drug interactions between topiramate and other medications or other anticonvulsants. Side effects include drowsiness, nausea, dizziness, coordination problems (e.g., loss of balance), impaired speech (e.g., aphasia), changes in taste, weight loss, and kidney stones. Children may have difficulty concentrating and may become aggressive. Acute glaucoma and visual abnormality, a potentially very serious complication, has been reported in a small number of patients. If abnormal visual symptoms occur, patients should notify a physician immediately.

Gabapentin (Neurontin®)—This drug is indicated for the adjunct 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 is taken 3 times daily.

No laboratory monitoring of liver, kidney, or blood (hematologic) function is necessary. Side effects include fatigue, dizziness, and imbalance.

Lamotrigine (Lamictal®)—This drug is indicated for the adjunct treatment of partial seizures and for conversion to monotherapyin adults with partial seizures. Its precise mechanism of action is unknown. It is presently available in oral form and is taken twice daily. No laboratory monitoring of drug levels are necessary.

Side effects include headache, nausea, dizziness, and skin rash. The appearance of the potentially life-threatening skin rash, particularly for patients who also are taking valproate (Depakote®), should be reported immediately to a physician.

Lacosamide (Vimpat®)—This drug is approved as adjunctive therapy for partial onset seizures in people 17 years of age and older. It is available in oral tablets and in an injectable form, and is usually administered twice per day. Side effects of lacosamide include the following:

Dizziness (vertigo)
Double vision
Excessive sleepiness (somnolence)
Fatigue
Headache
Nausea and vomiting

Tiagabine (Gabitril®)—This drug is indicated for adjunct 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 2 to 4 times daily.

No laboratory monitoring of tiagabine levels are necessary. Its metabolism may be altered when taken with other anticonvulsants. Side effects include dizziness and somnolence.

Levetiracetam (Keppra®)—This drug is approved for use in adults and children 4 years of age and older as adjunct therapy for the treatment of partial seizure disorders. It is available in tablet form and as an oral solution for patients who prefer a liquid or cannot swallow tablets, taken twice a day. Side effects can include fatigue, imbalance, and behavioral changes, which often dissipate after the first month of treatment.

Oxcarbazepine (Trileptal®)—This drug is indicated for monotherapy (used alone) and adjunct therapy (in addition to other medications) in adults who have partial seizures and as adjunct therapy in children aged 4 and older who have partial seizures.

Side effects are usually mild or moderate and include the following:

Abdominal pain, nausea, vomiting
Dizziness
Double vision
Drowsiness, fatigue
Hyponatremia
Loss of coordination, abnormal gait

Zonisamide (Zonegram®)—This drug is approved for use in adults as adjunct 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. Zonisamide is taken twice a day. Side effects can include dizziness, imbalance, weight loss, and fatigue. Patients who are allergic to sulfonamide drugs should not use zonisamide because it is a derivative of this class of drug.

Pregabalin (Lyrica®)—This drug is approved for use in adults as adjunct therapy for partial onset seizures. Lyrica, which is also used to treat diabetic peripheral neuropathy and postherpetic neuralgia, can be taken 2 or 3 times a day.

Side effects include the following: