Background Valproic acid (VPA) is widely prescribed by paediatric neurologists as an antiepileptic drug. VPA-induced hyperammonaemia can lead to encephalopathy and coma; it is well documented among the paediatric population. Severe urea cycle enzyme deficiencies are often revealed in early youth when VPA is administered. Such mild genetic deficiencies can remain unnoticed until adulthood and be discovered if VPA is taken for bipolar disorder.
Purpose To evaluate the frequency of VPA-induced hyperammonaemia in adult psychiatric settings and to sensitise the medical community to a potentially severe adverse effect of a widely-prescribed drug.
Materials and Methods The study was carried out a two-week period in a psychiatric hospital. It included every full-time hospitalised patient treated with VPA for at least 4 days (corresponding to 5 drug half-lives). Ammonia and VPA blood measurements were performed once and an electroencephalogram when ammonia exceeded 70 µM (normal range: 10 to 35 µM). Ethics committee approval was obtained before starting the study.
Results 122 patients were included in this study. 68 patients (55.8%) presented ammonia blood levels exceeding 35 µM and 4 of them (3.3%) exceeded 70 µM. One patient reached 118 µM one week after VPA initiation. No encephalographic abnormalities were observed. No correlation was found between ammonia and total VPA levels. Different oral forms of VPA were used and this study showed that they affected VPA blood levels.
Conclusions VPA-induced hyperammonaemia is a frequent, generally well-tolerated, adverse effect. Ammonia blood level monitoring combined with clinical monitoring are essential to avoid hyperammaonemic encephalopathy. Communication within the hospital led to the medical community becoming aware of the problem and new monitoring recommendations were defined including initial ammonia level measurement after VPA initiation and biannual monitoring of this biological parameter. Total VPA level determination doesn’t seem to be useful for predicting hyperammonaemia whereas the importance of measuring the free VPA has recently been highlighted.
No conflict of interest.
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