Atomoxetine Treatment of Attention Deficit/Hyperactivity Disorder Symptoms in 3-6-Year-Old Children with Autism Spectrum Disorder: A Retrospective Cohort Study.

Atomoxetine is indicated for the management of attention deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6 to 18 years. Few studies have assessed the safety and tolerability of atomoxetine in younger patients. This retrospective cohort study included 133 children aged 3-6 years who were diagnosed with ADHD comorbid with autism spectrum disorder (ASD). The primary endpoint was the evaluation of the safety profile of atomoxetine. In total, 50 patients (37.6%) experienced adverse events (AEs), which led to treatment discontinuation in 23 patients (17.3%). The most common AEs were gastrointestinal (24.1%), aggression or hostility (12.8%), and increased hyperactivity (9.0%). In the 23 patients who discontinued treatment, all the AEs resolved after treatment ceased. Among the 110 patients who completed at least 6 months' treatment, atomoxetine titrated to a dose of 1.2-1.8 mg/kg/day appeared to be well tolerated and effective. The Clinical Global Impression-Improvement score improved to 1 ("very much improved") and 2 ("much improved") in 62.4% and 20.3% of children, respectively, at their last visit. Overall, atomoxetine appeared to be well tolerated in younger children with comorbid ADHD and ASD. Nevertheless, close patient monitoring remains essential, and the study limitations necessitate caution in generalizing these findings to broader populations. Long-term prospective studies are required.

The Role of Clinical Pharmacist in Pediatrics' Adherence to Antiepileptic Drugs.

Background: Rate of nonadherence to antiepileptic drugs (AEDs) in children is about 33%. Engaging clinical pharmacists in the management of patients has proved to increase adherence to medications which will improve the outcomes of treatment. Objectives: To investigate the effect of a clinical pharmacist-led education on the adherence to AEDs in pediatric patients with epilepsy. Secondary outcomes include effectiveness and safety of AEDs, satisfaction with information about AEDs provided to the caregivers, and patients quality of life (QoL). Methods: This was an interventional study where pediatric patients were randomly assigned to the intervention (n = 41) or the control (n = 40) group. A 30-minute clinical pharmacist-led educational interview to the parent/caregiver was provided to the first group as add-on to standard medical care received by latter. Outcomes were measured at baseline and after 8-week follow-up. Results: The intervention group had an increase in mean adherence score from 6 ± 1.09 at baseline to 7.6 ± 0.9 at follow-up (P value < 0.001), while the control group had no significant change (P value > 0.05), the difference between the 2 groups at follow-up was significant (P value < 0.0001). No significant difference was observed between groups at follow-up with regard to effectiveness (P value > 0.05), and safety (P value = 0.08). While higher satisfaction with information (P value < 0.0001), and higher QoL (P value < 0.05) was observed in the intervention group. Conclusion and relevance: Clinical pharmacist-led education had a positive outcome on pediatric patients with epilepsy with regard to adherence, effectiveness, safety, satisfaction with information about AEDs, and QoL.

Genetic Association of Epilepsy and Anti-Epileptic Drugs Treatment in Jordanian Patients.

PURPOSE: The aim of this study was to investigate the possible effects of single-nucleotide polymorphisms (SNPs) within SLC1A1, SLC6A1, FAM131B, GPLD1, F2, GABRG2, GABRA1, and CACNG5 genes on response to anti-epileptic drugs (AEDs) and the genetic predisposition of epilepsy in Jordanian patients. PATIENTS AND METHODS: A total of 299 healthy individuals and 296 pediatric patients from the Jordanian population were recruited. Blood samples are collected, and genotyping was performed using a custom platform array analysis. RESULTS: The SLC1A1 rs10815018 and FAM131B rs4236482 polymorphisms found to be associated with epilepsy susceptibility. Moreover, SLC1A1 rs10815018 and GPLD1 rs1126617 polymorphisms were associated with generalized epilepsy (GE), while FAM131B rs4236482 is associated with the focal phenotype. Regarding the therapeutic response, the genetic polymorphisms of FAM131B rs4236482, GABRA1 rs2279020, and CACNG5 rs740805 are conferred poor response (resistance) to AEDs. There was no linkage of GLPD1 haplotypes to epilepsy, its subtypes, and treatment responsiveness. CONCLUSION: Our findings suggested that SLC1A1, FAM131B, and GPLD1 polymorphisms increasing the risk of generating epilepsy, while FAM131B, GABRA1, and CACNG5 variants may play a role in predicting drug response in patients with epilepsy (PWE).

WITHDRAWN: Evaluation of the factors that may contribute to the responsiveness of anti-epileptic treatments in pediatric patients, a study from Jordan.

This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the publication of this paper, which had been rejected by the editor. This error bears no reflection on the editor. The publisher apologizes to the authors, editor and the readers for this unfortunate error. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Genetic polymorphisms of CYP3A5, CHRM2, and ZNF498 and their association with epilepsy susceptibility: a pharmacogenetic and case-control study.

BACKGROUND: A total of 50 million persons were diagnosed worldwide with epilepsy. One-third of them are experiencing debilitating seizures despite optimum anti-epileptic drugs (AEDs) treatment. Several studies have suggested that CYP3A5, CHRM2, and ZNF498 influence the pharmacokinetics of AEDs. Therefore, the severity of the disease as well as the degree of response to the AEDs could be affected by the genetic polymorphisms within these genes. OBJECTIVES: In this study, we assessed the effect of certain single nucleotide polymorphisms (SNPs) within CYP3A5, CHRM2, and ZNF498 genes on the susceptibility to develop epilepsy and the responsiveness to AEDs treatment. METHODS: A case-control and pharmacogenetic study was conducted on samples of 299 healthy individuals in addition to 296 epileptic patients. Genotypic, allelic, and clinical data association were performed for the selected polymorphisms within the (rs324649, rs420817, rs15524, and rs1859690) in the Jordanian population. RESULTS: The analysis revealed no significant association of the investigated SNPs with epilepsy in general, partial and generalized epilepsy as well as drug responsiveness. CYP3A5 and ZNF498 were associated with family history (P=0.003 and P=0.002, respectively) and the classification of epilepsy for the ZNF498 variant (P=0.009). On the other hand, CHRM2 was not linked to either disease severity or treatment responsiveness. CONCLUSION: Our results failed to confirm the association of CYP3A5, ZNF498, and CHRM2 variants with either disease development or treatment response. Clinical pharmacogenetic studies may contribute to treatment personalization, appropriate drug dose selection, minimizing drug adverse reactions, increasing drug efficacy, and reducing the costive burdens.

Effects of MTHFR and ABCC2 gene polymorphisms on antiepileptic drug responsiveness in Jordanian epileptic patients.

BACKGROUND: Epilepsy is one of the most common neurological diseases with unclear etiology where its genetic background and treatment regime still need further exploration. OBJECTIVES: This study designed to evaluate the pharmacogenomics of MTHFR and ABCC2 genes, and their association with epilepsy susceptibility among Jordanian population. METHODS: A case-control study was conducted on Jordanian cohort of 296 epileptic patients and 299 healthy individuals. Custom platform array was used to genotype the genetic polymorphisms within MTHFR (rs1801133) and ABCC2 (rs717620, rs3740066, rs2273697) genes. RESULTS: This study revealed a significant genetic association of MTHFR rs1801133 polymorphism with susceptibility to generalized in general and generalized tonic-clonic epilepsy (GTCE)(p=0.018 and 0.01, respectively). Regarding ABCC2 gene, rs717620 was of linkage with generalized and GTCE subtypes (p=0.045 and 0.048, respectively), while rs717620 was associated with poor responder patients (p=0.036) with no linkage of the ABCC2 haplotypes. CONCLUSIONS: MTHFR and ABCC2 polymorphisms showed an association with either epilepsy types in general or subtypes and treatment response among Jordanian population. This study also suggested that these gene polymorphisms have an important role in epilepsy development and drug effectiveness and could be of a great impact in the era of epilepsy diagnosis and treatment.

The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy.

This study aims to investigate the effects of the three potassium channel genes KCNA1, KCNA2, and KCNV2 on increased susceptibility to epilepsy as well as on responsiveness to antiepileptic drugs (AEDs). The pharmacogenetic and case-control cohort (n = 595) consisted of 296 epileptic patients and 299 healthy individuals. Epileptic patients were recruited from the Pediatric Neurology clinic at the Queen Rania Al Abdullah Hospital (QRAH) in Amman, Jordan. A custom platform array search for genetic association in Jordanian-Arab epileptic patients was undertaken. The MassARRAY system (iPLEX GOLD) was used to genotype seven single nucleotide polymorphisms (SNPs) within three candidate genes (KCNA1, KCNA2, and KCNV2). Only one SNP in KCNA2, rs3887820, showed significant association with increased risk of susceptibility to generalized myoclonic seizure (p-value < 0.001). Notably, the rs112561866 polymorphism of the KCNA1 gene was non-polymorphic, but no significant association was found between the KCNA1 (rs2227910, rs112561866, and rs7974459) and KCNV2 (rs7029012, rs10967705, and rs10967728) polymorphisms and disease susceptibility or drug responsiveness among Jordanian patients. This study suggests that a significant association exists between the KCNA2 SNP rs3887820 and increased susceptibility to generalized myoclonic seizure. However, the present findings indicate that the KCNA1 and KCNV2 SNPs do not influence disease susceptibility and drug responsiveness in epileptic patients. Pharmacogenetic and case-control studies involving a multicenter and multiethnic approach are needed to confirm our results. To improve the efficacy and safety of epilepsy treatment, further studies are required to identify other genetic factors that contribute to susceptibility and treatment outcome.

Clinical profile of infants with hypsarrhythmia.

OBJECTIVE: The present study was done in order to obtain a baseline profile of infantile spasms and associated neurological disorders. PATIENT AND METHODS: The study included 50 patients with infantile spasm in Queen Rania Hospital for children in Jordan. The following data were obtained: sex, age at onset of spasms, details of seizure, family history of epilepsy, significant pre-/peri/ post-natal insults, Electroencephalography and detailed neuro imaging evaluation , detailed neurological, neuro developmental ,assessment were done by. Broad categories of possible etiologies were used the results were recorded for further study. RESULTS: Age of onset of infantile spasms ranged from 1month to 1 year and 6 months , (mean 4.8 months). The mean time of presentation was 9.4 months . A male preponderance was noted (74 %). flexor spasms (52%) was the commonest . Other types of seizures also accompanied infantile spasm in 44% children . (84%) were born of normal delivery, History of birth asphyxia was obtained in 48%, 3 (6%) had positive family history Developmental delay was recognized prior to onset of spasms in 52%, microcephaly was the commonest associated problem, Imaging studies of the brain revealed abnormality in 18 patients. 78% patients were classified as symptomatic and 22 % as cryptogenic. CONCLUSION: the pattern of infantile spasm in our country do not differ from that of developed countries, further researches is required to prevent both chronic epilepsy and psychomotor retardation and .preventive measurement to prevent birth asphyxia is recommended.