From the Guidelines
Yes, valproic acid (Valproate) can cause triphasic waves on electroencephalogram (EEG). This is supported by a study published in Liver International in 2009 1, which notes that triphasic waves can be observed in other types of metabolic encephalopathies or in drug intoxications, including valproate.
Key Points to Consider
- Triphasic waves are characterized by high-amplitude, positive-negative-positive waveforms that typically occur at a specific frequency
- The mechanism likely involves valproic acid's enhancement of inhibitory GABAergic neurotransmission, which can alter normal brain electrical activity, as suggested by the observation that benzodiazepine administration can give rise to similar EEG changes 1
- If triphasic waves are observed in a patient on valproic acid, clinicians should check drug levels, assess liver function, and consider whether the patient is experiencing encephalopathy, given that these EEG changes are usually reversible with dose reduction or discontinuation of the medication
- It's essential to distinguish medication-induced triphasic waves from those caused by metabolic encephalopathy to avoid unnecessary diagnostic workups or treatment changes, highlighting the importance of a thorough clinical assessment in such cases 1
From the Research
Valproic Acid and Triphasic Waves on EEG
- Valproic acid (VPA) has been associated with the presence of triphasic waves on electroencephalogram (EEG) in patients with valproate-induced hyperammonemic encephalopathy 2, 3.
- Triphasic waves are a characteristic EEG finding in severe encephalopathy, and their presence in patients taking VPA should prompt investigation for hyperammonemia and other signs of encephalopathy 3.
- The exact mechanism by which VPA causes triphasic waves is not fully understood, but it is thought to be related to the inhibition of carbamoylphosphate synthetase-I, leading to hyperammonemia and subsequent astrocyte swelling and cerebral edema 3.
- Other factors, such as polytherapy with other antiepileptic drugs, may also contribute to the development of triphasic waves in patients taking VPA 3.
Clinical Significance of Triphasic Waves
- Triphasic waves are often seen in patients with toxic-metabolic encephalopathies, including hepatic, uremic, and sepsis-associated encephalopathies 4.
- The presence of triphasic waves on EEG is highly suggestive of a toxic-metabolic encephalopathy, and their resolution is often associated with clinical improvement 2, 3.
- Atypical triphasic waves have been described in various conditions, including Angelman syndrome, toxic encephalopathies, and cerebrovascular disorders 4.
Management and Prevention
- Discontinuation of VPA is often necessary in patients who develop triphasic waves and hyperammonemic encephalopathy 2, 3.
- Monitoring of serum ammonium levels, liver function tests, and EEG is essential in patients taking VPA, particularly those with predisposing factors for hyperammonemia 3, 5.
- Therapeutic drug monitoring and routine liver biochemistry monitoring may help improve the safety profile of VPA and prevent the progression of liver injury 6, 5.