There are no official guidelines to assist in answering this question. I will search for relevant research papers instead.
From the FDA Drug Label
The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.
The FDA drug label does not directly answer whether elevated valproate levels can cause seizures. However, it does mention that the benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions, implying that higher doses may not always be beneficial and could potentially lead to adverse effects, but it does not specifically state that elevated valproate levels can cause seizures 1.
From the Research
Elevated Valproate Levels and Seizure Risk
- Elevated valproate levels can be associated with adverse effects, but the relationship between high valproate levels and seizure risk is complex 2, 3, 4.
- Studies suggest that valproate has a low potential for pharmacodynamic paradoxical seizure aggravation, and most cases of seizure aggravation occur in specific clinical contexts such as overdose, encephalopathy, hepatopathy, or metabolic disorders 3.
- Valproate is a broad-spectrum antiepileptic drug effective against various seizure types, and its efficacy is comparable to other antiepileptic drugs in patients with newly diagnosed partial seizures and/or primarily generalized tonic-clonic seizures 4.
Factors Influencing Valproate-Associated Seizure Risk
- Certain genetic polymorphisms, such as CYP2C9*2 and *3, may influence the risk of valproate-associated adverse drug reactions, including seizures, in individuals with epilepsy 5.
- However, the presence of these polymorphisms does not appear to significantly affect steady-state plasma valproate concentrations 5.
- Other factors, such as patient tolerance, dosage, and concomitant medication use, may also impact the risk of seizures associated with valproate treatment 4, 6.
Clinical Considerations
- Valproate is generally well-tolerated, but it can cause adverse effects such as gastrointestinal disturbances, tremor, and body weight gain 4.
- Serious adverse effects, including hepatotoxicity and teratogenicity, can occur, especially in high-risk patient populations 2, 4, 6.
- Clinicians should carefully monitor patients receiving valproate, especially those with intellectual disability or other underlying medical conditions, to minimize the risk of adverse effects and optimize treatment outcomes 6.