de Miguel Laura, Ballester Pura, Egoavil Cecilia, Sánchez-Ocaña María Luisa, García-Muñoz Ana María, Cerdá Begoña, Zafrilla Pilar, Ramos Enrique, Peiró Ana M
Pharmacogenetic Unit, Clinical Pharmacology Department, Alicante Institute for Health and Biomedical Research (ISABIAL), General University Hospital of Alicante, c/Pintor Baeza, 12, 03010 Alicante, Spain.
Clinical Pharmacology, Toxicology and Chemical Safety Unit, Institute of Bioengineering, Miguel Hernández University, Avda. de la Universidad s/n, 03202 Elche, Spain.
Pharmaceuticals (Basel). 2023 Oct 20;16(10):1496. doi: 10.3390/ph16101496.
Up to 73% of individuals with autism spectrum disorder (ASD) and intellectual disability (ID) currently have prescriptions for psychotropic drugs. This is explained by a higher prevalence of medical and psychiatric chronic comorbidities, which favors polypharmacy, increasing the probability of the appearance of adverse events (AEs). These could be a preventable cause of harm to patients with ASD and an unnecessary waste of healthcare resources.
To study the impact of pharmacogenetic markers on the prevention of AE appearance in a population with ASD and ID.
This is a cross-sectional, observational study (n = 118, 72 participants completed all information) in the ASD population. Sociodemographic and pharmacological data were gathered. The Udvalg for Kliniske Undersøgelser Scale (UKU Scale) was used to identify AEs related to the use of psychotropic medication. Polymorphisms of , , and were genotyped and correlated with the AE to find candidate genes. Furthermore, a review of all medications assessed in a clinical trial for adults with autism was performed to enrich the search for potential pharmacogenetic markers, keeping in mind the usual medications.
The majority of the study population were men (75%) with multiple comorbidities and polypharmacy, the most frequently prescribed drugs were antipsychotics (69%); 21% of the participants had four or more AEs related to psychotropic drugs. The most common were "Neurological" and" Psychiatric" (both 41%). Statistical analysis results suggested a significant correlation between the neurological symptoms and the genotype, given that they are not equally distributed among its allelic variants. The final review considered 19 manuscripts of medications for adults with ASD, and the confirmed genetic markers for those medications were consulted in databases.
A possible correlation between neurologic AEs and polymorphisms of was observed; therefore, studying this gene could contribute to the safety of this population's prescriptions. The following studies are underway to maximize statistical power and have a better representation of the population.
目前，高达73%的自闭症谱系障碍（ASD）和智力残疾（ID）患者正在服用精神药物。这是由于内科和精神科慢性合并症的患病率较高，这有利于联合用药，增加了出现不良事件（AE）的可能性。这些不良事件可能是对ASD患者造成伤害的一个可预防原因，也是医疗资源的不必要浪费。
研究药物遗传学标志物对预防ASD和ID人群中不良事件出现的影响。
这是一项针对ASD人群的横断面观察性研究（n = 118，72名参与者完成了所有信息）。收集了社会人口统计学和药理学数据。使用乌普萨拉监测中心量表（UKU量表）来识别与使用精神药物相关的不良事件。对、和的多态性进行基因分型，并将其与不良事件进行关联以寻找候选基因。此外，对一项针对成年自闭症患者的临床试验中评估的所有药物进行了综述，以丰富对潜在药物遗传学标志物的搜索，同时考虑常用药物。
研究人群中的大多数为男性（75%），患有多种合并症且联合用药，最常开具的药物是抗精神病药物（69%）；21%的参与者有四种或更多与精神药物相关的不良事件。最常见的是“神经学”和“精神学”不良事件（均为41%）。统计分析结果表明，神经学症状与基因型之间存在显著相关性，因为它们在其等位基因变体中分布不均。最终综述考虑了19篇关于成年ASD患者药物治疗的手稿，并在数据库中查阅了这些药物的已确认基因标志物。
观察到神经学不良事件与的多态性之间可能存在相关性；因此，研究该基因可能有助于提高该人群用药的安全性。后续研究正在进行中，以最大限度地提高统计效力，并更好地代表该人群。
