Valproic acid–induced hyperammonemia in neuropsychiatric disorders: a 2-year clinical survey

• Published in: Psychopharmacology 2023, Vol.240 (1), p.149-156
• Main Authors: Hosseini, Helia, Shafie, Mahan, Shakiba, Alia, Ghayyem, Hani, Mayeli, Mahsa, Hassani, Matineh, Aghamollaii, Vajiheh
• Format: Article
• Language: English
• Subjects: Adverse and side effects; Ammonia; Ammonia - adverse effects; Anticonvulsants - adverse effects; Biomedical and Life Sciences; Biomedicine; Complications and side effects; Demography; Divalproex; Drug therapy; Drugs; Epilepsy - drug therapy; Humans; Hyperammonemia; Hyperammonemia - chemically induced; Hyperammonemia - drug therapy; Mental disorders; Neurosciences; Organic mental disorder; Original Investigation; Patients; Pharmacology/Toxicology; Psychiatry; Risk factors; Risperidone; Risperidone - therapeutic use; Statistics; Valproic acid; Valproic Acid - adverse effects
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-022-06289-0

Introduction Valproic acid (VPA)–induced hyperammonemia (HA) is a rare adverse effect reported even at therapeutic VPA levels. The present study aimed to investigate the characteristics of VPA-induced HA and its association with the total dose, duration, and level of VPA. This study also investigated whether the use of VPA in combination with other medications has any effect on elevating serum ammonia levels. Methods A total of 316 patients with a history of VPA prescribed for underlying neuropsychiatric disorders were found eligible for the study. Data including demographic information, medical history and diagnosis, VPA dosage, VPA treatment duration, VPA level, and ammonia serum level were extracted and reviewed from our hospital records. The history of other neuropsychiatric medications was also included. Results Among 316 patients receiving VPA, HA was observed in 54 (17%) patients, and 15 patients were symptomatic among them. There was no significant difference in demographics between symptomatic and asymptomatic HA groups except for the number of co-administrated medications ( p  = 0.044). Besides, VPA duration and dose did not show a significant difference between the two groups. Additionally, the VPA level was significantly higher in patients who used risperidone in addition to VPA ( p  = 0.019). Eventually, VPA level showed a significant association with ammonia level ( p  = 0.025) and symptomatic HA ( p  = 0.033) after adjusting for possible confounders. Conclusion VPA level showed a significant association with ammonia level and symptomatic HA. Moreover, co-administrated medications such as risperidone might have an impact on the serum level of VPA. Further studies are recommended to confirm these findings.