UNASSIGNED: Atomoxetine, a selective norepinephrine reuptake inhibitor for attention-deficit hyperactivity disorder, may lead to severe complications, notably cardiac issues, upon overdose. We present a unique case of venoarterial extracorporeal membrane oxygenation (VA-ECMO) rescue for atomoxetine-induced cardiogenic shock.
UNASSIGNED: We report a 30-year-old man who, after ingesting a significant overdose of atomoxetine, experienced seizures and severe cardiogenic shock, necessitating VA-ECMO for resuscitation. While prior reports have noted cardiovascular complications like QTc prolongation and Takotsubo cardiomyopathy following atomoxetine overdose, this case is notable for its life-threatening circulatory failure, which required ECMO intervention. Swift recognition coupled with VA-ECMO initiation, endoscopic medication removal, intravenous lipid emulsion, and activated charcoal may have played a pivotal role in stabilizing the patient and facilitating recovery.
UNASSIGNED: Healthcare practitioners should recognize the severe cardiac complications of atomoxetine overdose. Careful monitoring with ECG and echocardiography, along with providing intensive care, is crucial in managing critical cases.

Mice of two strains selected for successful solution of \"object permanence\" test and for lack of such solution demonstrated the differential reaction to injections of two drugs. The effects of injections of atomoxetine. which blocks the noradrenaline reuptake, and of \'non-benzodiazepine\" anxiolytic afobazol was different. The success of solutions increased in mice selected for this test \"non-solution\": and decreased or was inefficient in mice, selected for successful solution of object permanence cognitive test.

Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that has long been considered a concern only in the pediatric population. However, symptoms often sustain into adulthood and may require medication. For women with ADHD, this also means dealing with the disorder during the reproductive period. Medication safety during pregnancy and breastfeeding is a critical concern, and the potential transfer of ADHD medication to infants remains a topic of scientific interest. The quantification of ADHD medications in both maternal blood and breast milk are vital for understanding their pharmacokinetics and potential exposure risks for (nursing) infants. This review aims (1) to compile and critically assess existing research on the transfer of ADHD medications into breast milk and the potential implications for nursing infants and (2) to provide a comprehensive overview and discussion of the literature regarding the quantification of methylphenidate, amphetamine, atomoxetine, viloxazine, guanfacine, clonidine and bupropion in the blood, urine, oral fluid, and breast milk with liquid chromatography. A literature search was conducted using PubMed, Scopus, and Web of Science, to identify relevant articles published from January 2014 up to December 2023. We illustrate the lack of methods to simultaneously monitor multiple ADHD medications as well as the lack of developed methods for breast milk. Finally, we highlight the need for continued research to refine our understanding of medication transfer into breast milk and potential risks, and to develop clinical guidelines to support mothers with ADHD in making informed choices regarding medication use during pregnancy and lactation.

Prader-Willi syndrome (PWS) is a multisystemic disorder. Notably, many characteristic symptoms of PWS are correlated with locus coeruleus norepinephrine system (LC-NE) dysfunction, including impairment in arousal, learning, pain modulation, and stress-induced negative affective states. Although electrophysiological experiments in necdin-deficient mice, an established PWS animal model, have revealed decreased spontaneous neuronal firing activity in the LC and impaired excitability, the behavioral phenotypes related to LC-NE dysfunction remain unexplored. In this study, heterozygous necdin-deficient mice (B6.Cg-Ndntm1ky) were bred from wild-type (WT) females to generate WT (+m/+p) and heterozygous (+m/-p) animals. Compared to WT mice, Ndn + m/-p mice demonstrated impaired visual-spatial memory in the Y-maze test, reduced social interaction, impaired sexual recognition, and shorter falling latency on the Rotarod. Using the open field test (OFT) and elevated plus maze (EPM), we observed similar locomotion activity of Ndn + m/-p and WT mice, but Ndn + m/-p mice were less anxious. After acute restraint, Ndn + m/-p mice exhibited significant impairment in stress-induced anxiety. Additionally, the plasma norepinephrine surge following exposure to acute restraint stress was also impaired. Pretreatment with atomoxetine, a norepinephrine reuptake inhibitor aimed to enhance LC function, restored Ndn + m/-p mice to exhibit a normal response to acute restraint stress. Furthermore, by employing chemogenetic approaches to facilitate LC neuronal firing, post-stress anxious responses were also partially rescued in Ndn + m/-p mice. These data strongly suggest that LC dysfunction is implicated in the pathogenesis of stress-related neuropsychiatric symptoms in PWS. Manipulation of LC activity may hold therapeutic potential for patients with PWS.

BACKGROUND: There is insufficient replicated data to establish a relationship between the polymorphisms of SLC6A2 and CYP2D6 and the treatment responses of atomoxetine (ATX) in ADHD. We focused on evaluating the effect of top-line single nucleotide polymorphisms (SNPs) in SLC6A2 and CYP2D6 on the ATX treatment response in attention deficit and hyperactivity disorder (ADHD).
METHODS: Of 160 patient records, 34 patients who met the inclusion criteria were evaluated to determine the relationship between genotypes of ten SNPs (six of SLC6A2 and four of CYP2D6) and ATX treatment response. Additionally, the connection between SNPs of CYP2D6 and the severity of side effects associated with ATX was analyzed in 37 patients, including the 34 study patients, and three patients discontinued because of ATX-dependent side effects.
RESULTS: All six polymorphisms we studied in SLC6A2 were associated with the treatment response of ATX. Clinical improvement in oppositional defiant disorder symptoms of patients with ADHD was only observed in carriers of the homozygous \"C\" allele of rs3785143 (podd = 0.026). We detected an association between higher CGI-side-effect severity scores and the \"TT\" genotype of rs1065852 polymorphism in CYP2D6 (p = 0.043).
CONCLUSIONS: The findings of this study suggest that genotypes of polymorphisms within the SLC6A2 and CYP2D6 may play an influential role in treatment response or the severity of side effects associated with ATX in ADHD patients.

Attention deficits are frequently reported within the clinical autism population. Despite not being a core diagnostic feature, some aetiological theories place atypical attention at the centre of autism development. Drugs used to treat attention dysfunction are therefore increasingly prescribed to autistic patients, though currently off-label with uncertain efficacy. We utilised a rodent-translated touchscreen test of sustained attention in mice carrying an autism-associated R451C mutation in the neuroligin-3 gene (Nlgn3R451C). In doing so, we replicated their cautious but accurate response profile and probed it using two widely prescribed attention-modulating drugs: methylphenidate (MPH) and atomoxetine (ATO). In wild-type mice, acute administration of MPH (3 mg/kg) promoted impulsive responding at the expense of accuracy, while ATO (3 mg/kg) broadly reduced impulsive responding. These drug effects were absent in Nlgn3R451C mice, other than a small reduction in blank touches to the screen following ATO administration. The absence of drug effects in Nlgn3R451C mice likely arises from their altered behavioural baseline and underlying neurobiology, highlighting caveats to the use of classic attention-modulating drugs across disorders and autism subsets. It further suggests that altered dopaminergic and/or norepinephrinergic systems may drive behavioural differences in the Nlgn3R451C mouse model of autism, supporting further targeted investigation.

Atomoxetine is a psychostimulant drug used for the treatment of attention-deficit/hyperactivity disorder (ADHD) symptoms in people with autism. Herein, eco-friendly fluorescent carbon quantum dots (CQDs) were synthesized using black-eyed pea beans and characterized for the purpose of quantifying atomoxetine in pharmaceutical capsules and human plasma. The selectivity of these CQDs towards atomoxetine was improved by functionalizing their surface with an atomoxetine-tetraphenylborate ion complex. The quantification of atomoxetine is based on measuring the fluorescence quenching of the functionalized CQDs in response to varying concentrations of atomoxetine. The Stern-Volmer plot was employed to investigate the mechanism through which atomoxetine quenches the fluorescence intensity of the CQDs. The outcomes indicated a dynamic quenching mechanism. The applied method was optimized and validated in compliance with ICH requirements, resulting in excellent linearity across the concentration range of 50-800 ng/mL. The developed method was successfully used to quantify atomoxetine in pharmaceutical dosage form and human plasma with acceptable accuracy and precision outcomes. In addition, the method was applied for clinical pharmacokinetic study of atomoxetine in the plasma of children diagnosed with both autism and ADHD. Atomoxetine was rapidly absorbed after a single oral dose of 10 mg, reaching maximum concentration within two hours and having a half-life (t1/2) of 3.11 h. Moreover, the method demonstrates a notable degree of eco-friendliness, as evidenced by two greenness evaluation metrics; Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE).

Many children with autism spectrum disorder (ASD) also have attention-deficit/hyperactivity disorder (ADHD). ADHD in children is associated with increased risk of negative outcomes, and early intervention is critical. Current guidelines recommend psychosocial interventions such as behavioral training as the first line of therapy in managing ADHD symptoms in children with or without ASD. Where symptoms are refractory to these interventions, medications such as stimulants, α2-adrenergic agonist inhibitors, selective norepinephrine reuptake inhibitors, and second-generation antipsychotics are recommended. However, these pharmacotherapies do not have regulatory approval for use in children of preschool age, and evidence on their safety and efficacy in this population has historically been very limited. Since publication of the current guidelines in 2020, several new randomized controlled trials and real-world studies have been published that have investigated the efficacy and tolerability of these medications in preschool children with ADHD, with or without comorbid ASD. Here, we provide a review of the key findings of these studies, which suggest that there is growing evidence to support the use of pharmacological interventions in the management of ADHD in preschool children with comorbid ASD.

Intradialytic hypotension significantly affects patient safety and clinical outcomes during hemodialysis. Despite various pharmacological and nonpharmacological interventions, effective management remains elusive. In this report, we detail a case of intradialytic hypotension in a male patient in his 40s, undergoing hemodialysis with a history of polycystic kidney disease. Eight years ago, the patient underwent bilateral nephrectomy because of a severe cystic infection, after which his systolic blood pressure (BP) persistently remained at 50-70 mm Hg during dialysis sessions. The initial treatment strategy for hypotension included fludrocortisone, midodrine, and prednisolone, leading to a slight temporary increase in BP, which subsequently declined. As the patient\'s condition deteriorated, the administration of norepinephrine or dopamine became necessary to sustain BP during dialysis. Given the patient\'s resistance to these treatments, a daily dose of 25 mg of atomoxetine was introduced. Following this treatment, there was a gradual improvement in the patient\'s vertigo, weakness, and BP. This case illustrates that low-dose atomoxetine can alleviate symptoms and elevate BP in patients experiencing severe intradialytic hypotension during hemodialysis.

UNASSIGNED: Stimulants, including methylphenidate and amphetamines, are the first-line pharmacological treatment of ADHD in adults. However, in patients who do not respond or poorly tolerate stimulants, non-stimulant medications are usually recommended.
UNASSIGNED: The authors provide a narrative review of the literature on non-stimulant treatments for adult ADHD, including controlled and observational clinical studies conducted on adult samples. Atomoxetine has been extensively studied and showed significant efficacy in treating adult ADHD. Issues related to dosing, treatment duration, safety, and use in the case of psychiatric comorbidity are summarized. Among other compounds indicated for ADHD in adults, antidepressants sharing at least a noradrenergic or dopaminergic component, including tricyclic compounds, bupropion, and viloxazine, have shown demonstratable efficacy. Evidence is also available for antihypertensives, particularly guanfacine, as well as memantine, metadoxine, and mood stabilizers, while negative findings have emerged for galantamine, antipsychotics, and cannabinoids.
UNASSIGNED: While according to clinical guidelines, atomoxetine may serve as the only second-line option in adults with ADHD, several other nonstimulant compounds may be effectively used in order to personalize treatment based on comorbid conditions and ADHD features. Nevertheless, further research is needed to identify and test more personalized treatment strategies for adults with ADHD.