Generalized Tonic-Clonic Seizures Treatment & Management

A number of antiepileptic drugs (AEDs) are used for the treatment of generalized tonic-clonic seizures. The choice of drug should be tailored to the individual patient and to the epilepsy syndrome, not to the seizure type only.

Go to Epilepsy and Seizures, First Adult Seizure, and First Pediatric Seizure for an overview of these topics.

Valproic acid has been considered the AED of choice for patients who have multiple seizure types, including generalized tonic-clonic seizures (except in female patients with reproductive capability), since it treats a broad spectrum of seizure types, including myoclonic seizures. The unblinded, randomized, controlled Standard Antiepileptic and New Antiepileptic Drug (SANAD) study on the effectiveness of valproate, lamotrigine, or topiramate for generalized and unclassifiable epilepsy supported the primacy of valproate. ^[4]  The selection of AED has to be personalized for each patient due to side-effect profile (e.g., valproic acid can cause weight gain, so if the patient is obese it can worsen that medical issue).

Phenytoin and carbamazepine are reasonable second options among the older group of AEDs for partial to secondarily generalized seizures (focal to bilateral tonic clonic seizures). However, the newer medications (e.g., lamotrigine, topiramate, zonisamide, ^[5] levetiracetam) tend to work as well if not better and have better side-effect profiles, especially regarding long-term side effects. Phenobarbital is still used by many neurologists, though its adverse cognitive effects have led to a decline in its use.

Perampanel (Fycompa) is approved as adjunctive treatment for primary generalized tonic-clonic seizures in adults and children aged 12 years or older. Perampanel has also shown good efficacy in reducing partial seizures with secondary generalization.

The AED rufinamide (Banzel) has been approved as adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (LGS). ^{[6, 7]}  Another AED, clobazam (Onfi/Frisium), has been useful in seizures associated with LGS as well in the United States, but worldwide use of this drug for many years also suggests good coverage for primary generalized tonic-clonic seizures.

For refractory generalized epilepsy, felbamate also is used as an agent of last resort and is very effective. The potential adverse effects of felbamate necessitate very careful monitoring of blood counts and liver function tests.

Special considerations

Certain AEDs are enzyme inducers and decrease the levels of oral contraceptive agents. Warn patients of this and advise them to use additional contraceptive precaution while on enzyme-inducing agents such as phenytoin, carbamazepine, and phenobarbital.

The older first-generation AEDs (e.g., phenytoin, carbamazepine, phenobarbital, valproic acid, and topiramate) have a teratogenic risk that needs to be considered.

The US Food and Drug Administration (FDA) approval for vagus nerve stimulation (VNS) is for the adjunctive treatment of refractory partial seizures. Open-label VNS registry results have also shown that some patients with generalized tonic-clonic seizures respond well. In more than 20 years of clinical use in the United States, VNS has helped reduce seizures in many patients with primary generalized seizures.

No other surgical option exists for pure generalized tonic-clonic seizures. Patients must be carefully evaluated and may necessitate video-EEG because some partial seizures with quick secondary bilateral synchrony may be labeled as primary generalized tonic-clonic.

A ketogenic diet can be tried to improve seizure control in younger patients whose condition is refractory. The ketogenic diet was popularized at Johns Hopkins and spread widely. It was based on the observation that seizures improved during periods of starvation. Studies have shown a substantial reduction in seizure frequency in 50% of patients placed on the diet.

The exact mechanism by which this diet works is not known. The diet typically contains a fat-to-carbohydrate ratio of 4:1. This diet produces a ketotic state but provides adequate calories for nutrition from proteins and fat.

The ketogenic diet is used for intractable epilepsy, especially in childhood. It is less commonly prescribed for adults because the diet, being very restrictive, is very difficult to maintain. In adults, a high-protein low-carbohydrate diet is being studied.

Adverse effects are mainly gastrointestinal and include bloating, constipation, renal stones, and bone and weight loss. Urinary ketones are checked daily and need to be greater than 4+ (80-160 mg/dL.

In general related to diet, avoid excessive amounts of stimulants such as energy drinks.

Driving is restricted if patients are still having seizures affecting safe driving as per particular state laws. In addition, common-sense restrictions for patients with epilepsy should be followed, such as not operating dangerous equipment, not swimming alone, and not taking baths unsupervised, among others. Cooking with open flame may be dangerous, leading to burn injuries.

Surgical options for primary generalized seizures are limited to vagus nerve stimulation (VNS). 

Epileptic individuals should avoid alcohol due to its potential to interact with AEDs. Alcohol use, if sufficient, can also lower the seizure threshold.