From the Guidelines
Generalized epilepsy, which includes tonic-clonic and absence seizures, should be treated with broad-spectrum antiepileptic drugs (AEDs) such as valproic acid, lamotrigine, and levetiracetam, as these medications have been shown to be effective in controlling seizures and improving quality of life 1.
Treatment Options
- First-line medications include valproic acid (500-2000 mg/day divided twice daily), lamotrigine (100-400 mg/day divided twice daily), and levetiracetam (1000-3000 mg/day divided twice daily) 1.
- For absence seizures specifically, ethosuximide (500-1500 mg/day divided twice daily) is particularly effective.
- Treatment should begin with a single AED at a low dose, gradually increasing until seizures are controlled or side effects occur.
Management and Prevention
- Medication should be taken consistently at the same times each day to maintain therapeutic blood levels.
- Patients should avoid seizure triggers like sleep deprivation, excessive alcohol, and certain medications.
- Regular follow-up appointments are essential to monitor drug levels, assess efficacy, and manage side effects.
- Treatment is typically long-term, with consideration for medication withdrawal only after 2-5 years of seizure freedom and in consultation with a neurologist.
Patient Education
- Patients should wear medical alert identification and be educated about seizure first aid for family members.
- Education on the importance of adherence to medication regimens and lifestyle modifications to reduce seizure risk is crucial.
Recent Guidelines
- The 2024 clinical policy by the American College of Emergency Physicians (ACEP) emphasizes the importance of appropriate dosing of benzodiazepines as first-line treatment for recurrent seizures, with second-line treatment including agents such as phenytoin, levetiracetam, and valproic acid 1.
From the FDA Drug Label
The effectiveness of levetiracetam as adjunctive therapy (added to other antiepileptic drugs)in patients 6 years of age and older with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic (PGTC) seizures was established in one multicenter, randomized, double-blind placebo-controlled study, conducted at 50 sites in 8 countries Table 6: Median Percent Reduction From Baseline In PGTC Seizure Frequency Per Week Placebo(N=84) Levetiracetam(N=78)
- statistically significant versus placebo Percent reduction in PGTC seizure frequency 44.6% 77.6%* The percentage of patients (y-axis) who achieved ≥50% reduction in weekly seizure rates from baseline in PGTC seizure frequency over the entire randomized treatment period (titration + evaluation period) within the two treatment groups (x-axis) is presented in Figure 5 Figure 5: Responder Rate (≥50% Reduction From Baseline) In PGTC Seizure Frequency Per Week
- statistically significant versus placebo
Levetiracetam is effective in treating primary generalized tonic-clonic (PGTC) seizures in patients with idiopathic generalized epilepsy.
- The median percent reduction in PGTC seizure frequency was 77.6% for levetiracetam compared to 44.6% for placebo.
- A statistically significant decrease in PGTC frequency was observed in levetiracetam-treated patients compared to placebo-treated patients.
- The percentage of patients who achieved ≥50% reduction in weekly seizure rates from baseline in PGTC seizure frequency was statistically significant for levetiracetam compared to placebo 2.
Perampanel is also effective in treating primary generalized tonic-clonic (PGTC) seizures in patients with idiopathic generalized epilepsy.
- A statistically significant decrease in seizure rate was observed with perampanel compared to placebo.
- The median percent reduction from baseline in primary generalized tonic-clonic seizure frequency per 28 days during the treatment period was 38% for placebo and 76% for perampanel 3.
From the Research
Generalized Epilepsy
- Generalized epilepsy, including tonic-clonic and absence seizures, can be classified into specific epilepsy syndromes, such as childhood absence epilepsy, juvenile myoclonic epilepsy (JME), or generalized tonic-clonic seizures on awakening 4.
- Idiopathic generalized epilepsy should be distinguished from focal epilepsy with rapid secondary generalization, and diagnosis may require ambulatory EEG, video EEG monitoring, or neuroimaging studies 4.
Treatment Options
- Ethosuximide, valproate, or lamotrigine are appropriate first-line choices in the treatment of childhood absence epilepsy, with the specific medication chosen based on side effect profiles, dosing formulations, and titration schedules 4.
- Valproate is the most effective treatment for JME, although lamotrigine and topiramate may also be appropriate choices 4, 5.
- For generalized tonic-clonic seizures, valproate, lamotrigine, or topiramate may be used, with valproate being the most effective option 4, 5, 6.
Seizure Characteristics
- Absence seizures can evolve into generalized tonic-clonic activity, with EEG onset characterized by generalized 2.5-to 5-Hz spike-and-wave discharges 7.
- Generalized tonic-clonic seizures are common in patients with idiopathic generalized epilepsy, with a prevalence of 86% in one study 8.
- Risk factors for generalized tonic-clonic seizures include time since disease onset, age at onset, and seizure type 8.
Outcome and Management
- Seizure outcome in patients with idiopathic generalized epilepsy is not affected by the presence of generalized tonic-clonic seizures per se, but rather by how they are managed 8.
- Valproate has been shown to reduce the risk of experiencing generalized tonic-clonic seizures, and its use is recommended, particularly in women with idiopathic generalized epilepsy 8.
- Psychiatric comorbidities are common in adolescents and adults with genetic generalized epilepsies, and ongoing management requires consideration of psychosocial and behavioural factors 6.