Hosseini Helia, Shafie Mahan, Shakiba Alia, Ghayyem Hani, Mayeli Mahsa, Hassani Matineh, Aghamollaii Vajiheh
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
NeuroTRACT Association, Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Psychopharmacology (Berl). 2023 Jan;240(1):149-156. doi: 10.1007/s00213-022-06289-0. Epub 2022 Dec 2.
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.
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.
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.
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.
丙戊酸（VPA）诱发的高氨血症（HA）是一种罕见的不良反应，即使在治疗性VPA水平时也有报道。本研究旨在调查VPA诱发HA的特征及其与VPA总剂量、持续时间和水平的关联。本研究还调查了VPA与其他药物联合使用是否对血清氨水平升高有任何影响。
共有316例因潜在神经精神疾病而开具VPA处方的患者符合本研究条件。从我们医院的记录中提取并审查了包括人口统计学信息、病史和诊断、VPA剂量、VPA治疗持续时间、VPA水平和血清氨水平在内的数据。还包括其他神经精神药物的使用史。
在316例接受VPA治疗的患者中，54例（17%）观察到HA，其中15例有症状。除联合用药数量外，有症状和无症状HA组之间的人口统计学无显著差异（p = 0.044）。此外，两组之间的VPA持续时间和剂量无显著差异。此外，除VPA外还使用利培酮的患者的VPA水平显著更高（p = 0.019）。最终，在调整可能的混杂因素后，VPA水平与氨水平（p = 0.025）和有症状的HA（p = 0.033）显示出显著关联。
VPA水平与氨水平和有症状的HA显示出显著关联。此外，联合使用的药物如利培酮可能会影响VPA的血清水平。建议进一步研究以证实这些发现。
