processing.... Drugs & Diseases > Neurology Epilepsy and Seizures Treatment & Management Updated: Jul 26, 2022 Author: David Y Ko, MD; Chief Editor: Selim R Benbadis, MD more...
Share Email Print Feedback Close Facebook Twitter LinkedIn WhatsApp webmd.ads2.defineAd(id: 'ads-pos-421-sfp',pos: 421); Sections Epilepsy and Seizures Sections Epilepsy and Seizures Overview Practice Essentials
Background Pathophysiology Etiology Epidemiology Prognosis Patient Education Show All Presentation History
Physical Examination Overview of Epileptic Seizures Classification Focal-Onset Seizures Generalized-Onset Seizures Classification of Epileptic Syndromes Show All DDx Workup Approach Considerations
Prolactin Study Serum Studies of Anticonvulsant Agents Electroencephalography and Video-Electroencephalography Show All Treatment Approach Considerations
Anticonvulsant Therapy Anticonvulsants for Specific Seizure Types Anticonvulsants in Specific Patient Populations Discontinuing Anticonvulsant Agents Nonpharmacologic Management Lobectomy and Lesionectomy Activity Modification and Restrictions Long-Term Monitoring Show All Medication Medication Summary
Anticonvulsants, Other Anticonvulsants, Barbiturates Anticonvulsants, Benzodiazepine Anticonvulsants, Succinimide Anticonvulsants, Neuronal Potassium Channel Opener Anticonvulsants, Hydantoins GABA Receptor Positive Modulators Show All Questions & Answers References Treatment Approach Considerations The goal of treatment in patients with epileptic seizures is to achieve a seizure-free status without adverse effects. This goal is accomplished in more than 60% of patients who require treatment with anticonvulsants. Many patients experience adverse effects from these drugs, however, and some patients have seizures that are refractory to medical therapy. A 2017 study found that fewer than two thirds of patients with newly diagnosed epilepsy are seizure-free after 1 year. A smaller study published in 2000 found the seizure-free rate to be 64%, which is almost identical to the rate found in the newer study. [31]
For patients who have had more than 1 unprovoked seizure, treatment with an anticonvulsant is recommended. However, the standard of care for a single unprovoked seizure is avoidance of typical precipitants (eg, alcohol, sleep deprivation); anticonvulsants are not recommended unless the patient has risk factors for recurrence.
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The risk of recurrence in a person with 1 generalized tonic-clonic seizure, a normal EEG, a normal brain MRI, and no evidence of focal onset is about 15%; in this case, the patient is not treated. If a patient has all risk factors, the risk is approximately 80%, and the patient is treated.
The major unresolved question is how to treat patients with 1 abnormality, whose recurrence risk is 30-50%. One approach is to base the decision on a discussion with the patient that includes the risk of seizure recurrence, the risk of toxic effects from the anticonvulsant, and the benefits of avoiding another seizure. The clinician should also describe seizure precautions, including not driving for a specific time. Treatment with anticonvulsants does not alter the natural history of seizure recurrence; it only reduces the risk for the duration of treatment.
The First Seizure Trial Group randomly selected 397 patients with an unprovoked, generalized tonic-clonic first seizure to either receive prophylaxis with a conventional anticonvulsant (ie, carbamazepine, phenobarbital, phenytoin, valproic acid) or to receive no treatment and reported that about 18% of treated patients had seizure recurrence within 1 year, compared with 39% of untreated patients. [32] Therefore, patients must be told that anticonvulsants can reduce their risk of having another seizure but will not eliminate that risk.
The mainstay of seizure treatment is anticonvulsant medication. The drug of choice depends on an accurate diagnosis of the epileptic syndrome, as response to specific anticonvulsants varies among different syndromes. The difference in response probably reflects the different pathophysiologic mechanisms in the various types of seizure and the specific epileptic syndromes.
This section discusses the use of anticonvulsant agents for absence, tonic or atonic, myoclonic, and tonic-clonic seizures. A discussion of treatment for focal-onset seizures, including refractory cases, also follows, with some findings from the Veterans Administration (VA) Cooperative Studies and Standard and New Antiepileptic Drugs (SANAD) trial.
If only absence seizures are present, most neurologists treat them with ethosuximide. If absence seizures are present along with other seizure types (eg, generalized tonic-clonic seizures, myoclonic seizures), the choices are valproic acid, lamotrigine, or topiramate. Do not use carbamazepine, gabapentin or tiagabine, because these drugs may exacerbate absence seizures. It is uncertain whether pregabalin, a medication related to gabapentin, may also exacerbate this type of seizure.
Myoclonic seizures have a bimodal distribution. Infants with myoclonic epilepsies usually have a poor prognosis; however, in late childhood and adolescence, the syndrome of juvenile myoclonic epilepsy (JME) is often the cause of myoclonic seizures. The seizures associated with JME are usually readily controlled with the appropriate broad-spectrum antiepileptic drug (AED), but JME has a high recurrence rate of approximately 80-90% after discontinuation of anticonvulsants.
The best medications for JME and myoclonic seizures are valproic acid, lamotrigine, and topiramate. Levetiracetam is approved by the FDA for adjunctive therapy of JME; this is the first medication approved for this syndrome. Anecdotal evidence suggests that zonisamide might be helpful in JME. Note that if partial seizure medications, such as phenytoin and carbamazepine, are used to treat JME, these agents may not only be ineffective, but in certain cases they may exacerbate the seizures.
In focal-onset seizures, there are many AED choices with monotherapy indications, including carbamazepine, cenobamate, lacosamide, lamotrigine, oxcarbazepine, and topiramate. (see Anticonvulsants in Specific Patient Populations, below). Adjunctive therapy with levetiracetam, tiagabine, gabapentin, pregabalin, lacosamide, cenobamate, or ezogabine may be considered if the first or second monotherapy trial with first-line treatments fails. Discussing the adverse-effect profiles of anticonvulsants with patients is important, because the efficacies of anticonvulsants appear to be similar. [46]
The focal seizures arm of the SANAD trial demonstrated that although carbamazepine is the standard drug treatment, lamotrigine is clinically better with respect to time to treatment failure. [50] This study also determined that lamotrigine is a cost-effective alternative to carbamazepine for patients with focal-onset seizures. Carbamazepine, gabapentin, lamotrigine, oxcarbazepine, and topiramate were included for comparison. [50] However, the cost-effectiveness of medications has changed, as many new AEDs also have generic formulations.
Of the new anticonvulsants, lamotrigine and topiramate appear to have broad spectrum of action in many seizure types. [51, 52] The American Academy of Neurology and the American Epilepsy Society assembled a task force that reviewed the literature and provided evidence-based recommendations for monotherapy, adjunctive therapy, treatment of primary generalized seizures, treatment in children, and treatment of subgroups of new-onset and refractory epilepsy. [51, 52]
Although the term medically refractory epilepsy has been used for cases that fail to respond to three antiepileptic drugs, the International League Against Epilepsy (ILAE) has proposed defining drug-resistant epilepsy as the failure to achieve sustained seizure freedom despite adequate trials of two antiepileptic drugs, either as monotherapy or in combination. [56, 57] The drugs must have been appropriately chosen and used, and failure must have occurred because of lack of efficacy and not because of adverse effects.
A study of the ILAE criteria in pediatric epilepsy patients found that the probability of achieving seizure freedom was 65%, 29%, 27% and 21%, respectively, with trials of successive therapeutic regimens. [56, 57] Patients with medically refractory epilepsy should be referred to an epileptologist.
Immunotherapy may be a viable treatment strategy in a subset of epileptic patients whose seizures are refractory to management with conventional AEDs and whose poor seizure control may result from the presence of neural-specific antibodies. [59, 60] Iorio et al found autoantibodies specific to neural antigen in 2 of 29 patients with epilepsy and other neurologic symptoms and/or autoimmune diseases (group 1) and in 9 of 30 patients with AED-resistant epilepsy (group 2).
The recurrence rate during adulthood for patients with juvenile myoclonic epilepsy (JME) is about 80-90% in 2 years, even in patients who have spent many years being seizure free on low doses of appropriate anticonvulsants.
According to the manufacturer's registry, efficacy of the stimulating device at 18 months is 40-50%, where efficacy is defined as a seizure reduction of 50% or more. Many patients report improvement in seizure intensity and general mood. However, seizure-free rates for pharmacologically intractable focal-onset epilepsy are less than 10%.
Positive predictors of a favorable outcome with VNS therapy include posttraumatic epilepsy and tuberous sclerosis. Few patients achieve complete seizure freedom with VNS, and about a quarter of patients receive no benefit in their seizure frequency. [69] Some patients have clinical improvement in terms of milder and shorter seizures. 2ff7e9595c
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