ArticleFrontiers in pharmacology2025
What drives hyperammonemic encephalopathy in AED users: monotherapy risks or polypharmacy perils?
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Renally Generated Ammonia as a Cause of Hyperammonaemic Non-Hepatic Encephalopathy.Nephrology (Carlton, Vic.) · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background and objectives: Hyperammonemic encephalopathy (HE) is a serious side effect linked to sodium valproate (VPA). Recent case studies indicate that newer antiepileptic drugs (AEDs) might also trigger HE, whether used alone or alongside VPA. This study investigated the risk factors of HE linked to 10 AEDs using data from the FDA Adverse Event Reporting System (FAERS), focusing on VPA co-administration effects. Methods: FAERS reports from the first quarter of 2013 to the third quarter of 2024 were examined for ten frequently prescribed antiepileptic drugs (AEDs): VPA, perampanel (PER), phenytoin (PHT), carbamazepine (CBZ), topiramate (TPM), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXA), clonazepam (CZP), and zonisamide (ZNS). Hepatic event (HE) signals were evaluated using reporting odds ratios (ROR). A multivariate logistic regression analysis was conducted to assess risk factors (age, gender, indication, drug combinations). Particular attention was given to the effects of VPA in combination with LEV, TPM, olanzapine (OLZ), or quetiapine (QTP) on the risk of HE. Results: A total of 1,456 HE-related events were identified, with 93.06% of these events linked to AEDs. VPA had the highest association with HE (ROR = 122.14, 95% CI: 110.16-135.41), followed by PER, which was independent of VPA (ROR = 52.62). Eight additional AEDs also indicated positive associations, mainly influenced by VPA (such as TPM and LEV). Identified risk factors for HE included age (with a lower risk observed in minors, OR = 0.61, 95% CI [0.50-0.76]) and clinical indication (with a lower risk in psychiatric disorders, OR = 0.74, 95% CI [0.62-0.89]). The combination of VPA+TPM significantly raised the risk of HE (OR = 3.38, 95% CI [2.25-5.06]) without negatively impacting outcomes. Furthermore, combinations of antipsychotic medications with VPA also indicated an increased risk of HE (OLZ+VPA: OR = 1.65, 95% CI [1.18-2.30], QTP+VPA: OR = 1.95, 95% CI [1.39-2.75]). Conclusion: This research underscores the possible danger of HE related to AEDs, with a particular focus on the risks tied to VPA and PER when used alone, as well as VPA in conjunction with TPM, OLZ, or QTP. It emphasizes the need to monitor ammonia levels in patients on AEDs, particularly those on polypharmacy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.