From the Guidelines
Dose-related adverse reactions of antiseizure medications (ASMs) typically include ataxia and sedation, which are common dose-dependent side effects that can occur when medication levels exceed the therapeutic range. These reactions are predictable and dose-dependent, meaning they can often be managed by dose reduction rather than medication discontinuation. The most recent and highest quality study, 1, provides evidence that specific medications have characteristic adverse effects, such as phenytoin causing ataxia, and carbamazepine producing diplopia and hyponatremia. Other studies, such as 1 and 1, also support the idea that dose-related adverse reactions are a significant concern in the management of ASMs. Some key points to consider when managing ASMs include:
- Blood level monitoring is crucial for medications with established therapeutic ranges like phenytoin (10-20 μg/mL), carbamazepine (4-12 μg/mL), and valproate (50-100 μg/mL) 1.
- Dose adjustments should be made gradually to prevent breakthrough seizures, typically reducing by 25% increments while monitoring for improvement in adverse effects 1.
- The dose-dependent nature of these reactions occurs because higher medication concentrations lead to greater binding to both target and non-target receptors in the brain and other tissues, causing both therapeutic effects and unwanted side effects 1. Overall, the evidence suggests that ataxia and sedation are common dose-related adverse reactions of ASMs, and that careful management of medication levels and dose adjustments are necessary to minimize these effects.
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. Sedation usually abates upon reduction of other antiepileptic medication Tremor (may be dose-related), hallucinations, ataxia, headache, nystagmus, diplopia, asterixis, "spots before eyes", dysarthria, dizziness, confusion, hypesthesia, vertigo, incoordination, and Parkinsonism have been reported with the use of valproate. Table 3 lists treatment-emergent adverse events which were reported by ≥ 5% of patients in the high dose divalproex sodium group, and for which the incidence was greater than in the low dose group, in a controlled trial of divalproex sodium monotherapy treatment of complex partial seizures Nervous System Tremor5719 Somnolence3018 Dizziness1813
The dose-related adverse reactions of Antiseizure Medications (ASMs) are:
- Ataxia
- Sedation
- Tremor (may be dose-related)
- Dizziness
- Somnolence 2
From the Research
Dose-Related Adverse Reactions of Antiseizure Medications (ASMs)
The dose-related adverse reactions of antiseizure medications (ASMs) can vary depending on the specific medication and the individual patient. Based on the available evidence, the following dose-related adverse reactions have been reported:
- Ataxia and sedation are common dose-related adverse reactions of ASMs, particularly at higher doses 3, 4.
- Other dose-related adverse reactions of ASMs include:
- Neutropenia and thrombocytopenia, particularly with valproic acid 5.
- Kidney stones and rash, although these are not as commonly reported as ataxia and sedation 6.
- Weight gain and cognitive deficit, which can occur with certain ASMs, such as valproic acid and topiramate 6, 4.
- Irritability and constipation, which have been reported with some ASMs, although these are not as well-studied as other adverse reactions 7.
Comparison of Adverse Reaction Profiles
The adverse reaction profiles of different ASMs can vary significantly. For example:
- Levetiracetam has been associated with a higher risk of psychiatric adverse reactions, such as aggression, compared to lamotrigine 7.
- Carbamazepine and oxcarbazepine have been associated with higher rates of discontinuation due to adverse reactions, compared to levetiracetam and lamotrigine 7.
- Valproic acid has been associated with a higher risk of hematologic abnormalities, such as thrombocytopenia, compared to other ASMs 5.