From the Guidelines
Absence seizures can lead to significant complications, including learning difficulties and behavioral problems, and treating them with valproic acid (Valproate) may result in serious side effects such as hepatotoxicity and thrombocytopenia. When considering the treatment of absence seizures, particularly with valproic acid, it is crucial to weigh the potential benefits against the risks. The use of valproic acid has been associated with complications such as thrombocytopenia and hepatotoxicity, as noted in a 2021 study published in Neuro-Oncology 1.
Some key points to consider in the management of absence seizures with valproic acid include:
- Monitoring for side effects such as nausea, vomiting, tremor, weight gain, hair loss, and drowsiness
- Regular assessment of liver function and complete blood count to mitigate the risk of hepatotoxicity and thrombocytopenia
- Awareness of the potential for teratogenicity in women of childbearing age, emphasizing the need for effective contraception and pre-pregnancy counseling
- Consideration of alternative treatments for certain patient populations, such as children under two years of age or those with specific metabolic disorders, who may be at higher risk for valproate-induced hepatotoxicity
Given the potential complications associated with valproic acid, it is essential to closely monitor patients and adjust treatment regimens as necessary to minimize risks while effectively managing absence seizures. The dosing of valproic acid typically starts at 10-15 mg/kg/day and may be gradually increased to 30-60 mg/kg/day, divided into 2-3 doses, with therapeutic blood levels maintained between 50-100 μg/mL, although this should be tailored to the individual patient's response and tolerance.
From the FDA Drug Label
The administration of delayed-release divalproex sodium may result in reduction of gastrointestinal side effects in some patients. CNS Effects: Sedative effects have occurred in patients receiving valproate alone but occur most often in patients receiving combination therapy. Several reports have noted reversible cerebral atrophy and dementia in association with valproate therapy
- Complications of Absence Seizures treated with Valproic Acid:
- Gastrointestinal side effects
- CNS effects such as sedation, tremor, hallucinations, ataxia, headache, nystagmus, diplopia, asterixis, dysarthria, dizziness, confusion, and Parkinsonism
- Reversible cerebral atrophy and dementia
- Hyperammonemic encephalopathy, particularly in patients with underlying urea cycle disorders
- Serious skin reactions, including toxic epidermal necrolysis
- Psychiatric effects such as emotional upset, depression, psychosis, aggression, hyperactivity, hostility, and behavioral deterioration
- Hematologic effects such as thrombocytopenia, inhibition of platelet aggregation, and bleeding disorders
- Hepatic effects such as minor elevations of transaminases and potentially serious hepatotoxicity
- Endocrine effects such as irregular menses, secondary amenorrhea, breast enlargement, and galactorrhea
- Pancreatic effects such as acute pancreatitis
- Metabolic effects such as hyperammonemia, hyponatremia, and inappropriate ADH secretion
- Genitourinary effects such as enuresis and urinary tract infection
- Special senses effects such as hearing loss and ear pain 2
From the Research
Potential Complications of Absence Seizures
The potential complications of absence seizures, particularly when treated with valproic acid (Valproate), include:
- Thrombocytopenia, a condition characterized by a low platelet count, which can be a side effect of valproic acid therapy 3
- Antiepileptic hypersensitivity syndrome, a rare but potentially life-threatening condition that can occur with the use of certain antiepileptic drugs, including valproic acid 3
- Hepatotoxicity, a rare but potentially fatal side effect of valproic acid 4
- Hyperammonemia, a condition characterized by elevated levels of ammonia in the blood, which can be a side effect of valproic acid 4
Treatment-Related Complications
The treatment of absence seizures with valproic acid can also be associated with other complications, including:
- Lack of seizure control, which can occur in some patients despite treatment with valproic acid 5
- Intolerable adverse events, which can occur in some patients taking valproic acid 5
- Cognitive side effects, which can be a concern in patients with refractory absence seizures 6
Refractory Absence Seizures
In some cases, absence seizures can be refractory to treatment with valproic acid and other antiepileptic drugs. In these cases, the management of the condition can be challenging, and the priority should be to limit the cognitive side effects of the antiepileptic drugs 6. The treatment of refractory absence seizures may involve the use of alternative therapies, such as gabapentin, levetiracetam, tiagabine, topiramate, and zonisamide 3.