Clin Psychopharmacol Neurosci.  2022 Aug;20(3):536-547. 10.9758/cpn.2022.20.3.536.

Blood Levels of Ammonia and Carnitine in Patients Treated with Valproic Acid: A Meta-analysis

• Yokoyama S
• Sugawara N
• Maruo K
• Yasui-Furukori N
• Shimoda K

• KMID: 2532818
• DOI: http://doi.org/10.9758/cpn.2022.20.3.536

Abstract

Objective
Long-term valproic acid (VPA) administration is associated with adverse metabolic effects, including hyperammonemia and hypocarnitinemia. However, the pathogeneses of these adverse events remain unclear, and not enough reviews have been performed. The aim of this study was to conduct a meta-analysis of studies examining blood levels of ammonia and carnitine in patients treated with VPA.
Methods
We conducted database searches (PubMed, Web of Science) to identify studies examining blood levels of ammonia and carnitine in patients treated with VPA. A meta-analysis was performed to conduct pre- and post-VPA treatment comparisons, cross-sectional comparisons between groups with and without VPA use, and estimations of the standardized correlations between blood levels of ammonia, carnitine, and VPA.
Results
According to the cross-sectional comparisons, the blood ammonia level in the VPA group was significantly higher than that in the non-VPA group. Compared to that in the non-VPA group, the blood carnitine level in the VPA group was significantly lower. In the meta-analysis of correlation coefficients, the blood VPA level was moderately correlated with blood ammonia and blood free carnitine levels in the random effects model. Furthermore, the blood ammonia level was moderately correlated with the blood free carnitine level.
Conclusion
Although the correlation between ammonia and free carnitine levels in blood was significant, the moderate strength of the correlation does not allow clinicians to infer free carnitine levels from the results of ammonia levels. Clinicians should measure both blood ammonia and free carnitine levels, especially in patients receiving high dosages of VPA.

Keyword

Bipolar disorder; Valproic acid; Free carnitine; Acylcarnitine; Ammonia