Search

Background: Few biological or clinical predictors guide medication selection and/or dosing for attention-deficit/hyperactivity disorder (ADHD). Accumulating data suggest that genetic factors may contribute to clinically relevant pharmacodynamic (e.g., dopamine transporter—SLC6A3 also commonly known as DAT1) or pharmacokinetic (e.g., the drug metabolizing enzyme Cytochrome P450 2D6 CYP2D6) effects of methylphenidate (stimulant) and atomoxetine (non-stimulant), which are commonly prescribed medications. This is the first study of youth with ADHD exposed to both medications examining the clinical relevance of genetic variation on treatment response. Methods: Genetic variations in DAT1 and CYP2D6 were examined to determine how they modified time relationships with changes in ADHD symptoms over a 4-week period in 199 youth participating in a double-blind crossover study following a stepped titration dose optimization protocol. Results: Our results identified trends in the modification effect from CYP2D6 phenotype and the time–response relationship between ADHD total symptoms for both medications (atomoxetine [ATX]: p = 0.058, Methylphenidate [MPH]: p = 0.044). There was also a trend for the DAT1 3′ untranslated region (UTR) variable number of tandem repeat (VNTR) genotype to modify dose relationships with ADHD-RS total scores for atomoxetine (p = 0.029). Participants with DAT1 9/10 repeat genotypes had a more rapid dose–response to ATX compared to 10/10, while those with 9/9 genotypes did not respond as doses were increased. Regardless of genotype, ADHD symptoms and doses were similar across CYP2D6 metabolizer groups after 4 weeks of treatment. Conclusions: Most children with ADHD who were CYP2D6 normal metabolizers or had DAT1 10/10 or 9/10 genotypes responded well to both medications. While we observed some statistically significant effects of CYP2D6 and DAT1 with treatment response over time, our data indicate that genotyping for clinical purposes may have limited utility to guide treatment decisions for ATX or MPH because both medications were generally effective in the studied cohort after 3 weeks of titration to higher doses. The potential DAT1 association with ATX treatment is a novel finding, consistent with prior reports suggesting an association of the DAT1 in 9/9 genotypes with lower responsive rates to treatment at low and moderate doses. [ABSTRACT FROM AUTHOR]

Norepinephrine–dopamine reputake inhibitors (NDRIs), including bupropion, methylphenidate, atomoxetine, and reboxetine, are commonly prescribed for psychiatric disorders such as narcolepsy, attention-deficit/hyperactivity disorder, and depression. Cardiovascular adverse events have been reported to the FDA despite their effectiveness. This pharmacovigilance study analyzed cardiovascular adverse events associated with NDRIs using the FDA Adverse Event Reporting System data from January 2004 to December 2021. A retrospective analysis of adverse event reports was conducted, employing time-trend analysis and disproportionality evaluation to assess cardiovascular risks. Bupropion had the greatest reported odds ratios (RORs) for tachycardia (ROR = 4.2, 95% CI: 4.0–4.4) and hypertension (ROR = 3.5, 95% CI: 3.3–3.7), while methylphenidate showed greater ROR for arrhythmias (ROR = 2.8, 95% CI: 2.6–3.0) and palpitations (ROR = 3.1, 95% CI: 2.9–3.3). Reboxetine had signals for palpitations (ROR = 3.0, 95% CI: 2.8–3.2) and myocardial infarction (ROR = 2.7, 95% CI: 2.5–2.9), whereas atomoxetine revealed signals for hypertension (ROR = 2.9, 95% CI: 2.7–3.1) and syncope (ROR = 2.5, 95% CI: 2.3–2.7). Time-trend analysis revealed temporal variability in the cardiovascular risks connected with NDRIs. Our research elucidates cardiovascular safety profiles for NDRIs, highlighting the necessity for continuous pharmacovigilance. The observed variations in adverse events emphasize the need for ongoing surveillance to mitigate potential cardiovascular risks and enhance patient safety and treatment outcomes. [ABSTRACT FROM AUTHOR]

Purpose: We previously reported that single doses of the norepinephrine transporter inhibitor, atomoxetine, increased standing blood pressure (BP) and ameliorated symptoms in patients with neurogenic orthostatic hypotension (nOH). We aimed to evaluate the effect of atomoxetine over four weeks in patients with nOH. Methods: A randomized, double-blind, placebo-controlled crossover clinical trial between July 2016 and May 2021 was carried out with an initial open-label, single-dose phase (10 or 18 mg atomoxetine), followed by a 1-week wash-out, and a subsequent double-blind 4-week treatment sequence (period 1: atomoxetine followed by placebo) or vice versa (period 2). The trial included a 2-week wash-out period. The primary endpoint was symptoms of nOH as measured by the orthostatic hypotension questionnaire (OHQ) assessed at 2 weeks. Results: A total of 68 patients were screened, 40 were randomized, and 37 completed the study. We found no differences in the OHQ composite score between atomoxetine and placebo at 2 weeks (−0.3 ± 1.7 versus −0.4 ± 1.5; P = 0.806) and 4 weeks (−0.6 ± 2.4 versus −0.5 ± 1.6; P = 0.251). There were no differences either in the OHSA scores at 2 weeks (3 ± 1.9 versus 4 ± 2.1; P = 0.062) and at 4 weeks (3 ± 2.2 versus 3 ± 2.0; P = 1.000) or in the OH daily activity scores (OHDAS) at 2 weeks (4 ± 3.0 versus 5 ± 3.1, P = 0.102) and 4 weeks (4 ± 3.0 versus 4 ± 2.7, P = 0.095). Atomoxetine was well-tolerated. Conclusions: While previous evidence suggested that acute doses of atomoxetine might be efficacious in treating nOH; results of this clinical trial indicated that it was not superior to placebo to ameliorate symptoms of nOH. Trial registration: ClinicalTrials.gov; NCT02316821. [ABSTRACT FROM AUTHOR]

Non-stimulant atomoxetine is recognized in various current clinical guidelines as an important alternative to stimulants for the pharmacological treatment of attention deficit/hyperactivity disorder (ADHD) in children. While its efficacy and tolerability for core symptoms are established, there is considerable inter-individual variability in response and exposure, highlighting the need for personalized dosing. In this review, we evaluated existing studies and summarized comprehensive evidence supporting the clinical implementation of therapeutic drug monitoring (TDM) and personalized dosing of atomoxetine, organized around a series of logically structured questions. Although there are notable gaps in achieving personalized dosing across multiple critical elements, the available evidence is helpful to endorse personalized dose adjustments based on TDM and CYP2D6 genotyping "whenever possible." We advocate for ongoing improvement and enhancement in clinical practice. Future advancements will rely on a deeper understanding of ADHD, facilitating more precise diagnoses and personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Resistance acquired after radiotherapy is directly related to the failure of various cancer treatments, including GBM. Because the mechanism for overcoming radioresistance has not yet been clearly identified, the development of diagnostic and therapeutic markers to treat radioresistance is necessary. Since increased expression of stemness- and EMT-related markers are reported to be closely correlated with radioresistance, research is underway to develop new drugs targeting these factors. Methods: To develop an anticancer drug that overcomes radioresistance, a library of drugs already approved by the FDA was used. After treating radioresistant GBM cells with each drug, the expression of stemness- and EMT-related markers was confirmed by qRT-PCR, and as a result, Atomoxetine (ATX) was selected. It was confirmed that radioresistance-induced cell migratory, invasive, sphere formation abilities, and tumor growth using a xenograft mouse model were suppressed upon ATX treatment. Using a miRNA prediction tool, we discovered miR-520d-5p, which targets Notch2 and Hey1, key factors in radioresistance, and discovered circATIC targeting this miRNA, revealing its relationship with ATX. We demonstrated the expression regulation mechanism and signaling mechanism between circATIC, miR-520d-5p, Notch2, and Hey1 factors using a luciferase reporter assay. In addition, the results at the cellular level were clinically verified by confirming the correlation between radiation, miR-520d-5p, and circATIC using patient plasma by qRT-PCR. Results: ATX showed potential as a treatment for radioresistance by suppressing the malignant phenotype by regulating the circATIC/miR-520d-5p/Notch2-Hey1 signaling mechanism in vitro and in vivo using radioresistant GBM cells. Conclusions: This study revealed that ATX suppresses radioresistance through the circATIC/miR-520d-5p/Notch2-Hey1 signaling pathway. These results showed the potential of ATX as a new drug that can overcome radioresistance, a major challenge in cancer treatment, and the signaling factors identified in this mechanism suggest the possibility of use as potential targets for the diagnosis and treatment of radioresistance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Atomoxetine (ATX), a selective noradrenaline re-uptake inhibitor, is a preferred drug with sufficient efficacy and favorable safety profile for the treatment of attention-deficit hyperactivity disorder. Ejaculatory dysfunctions have been reported in the patients receiving ATX as sexual side effects, of which underlying mechanisms are largely unknown. The present study aimed to investigate the effect of ATX on mouse isolated vas deferens (VD) contractility as a potential mechanism of ATX-induced ejaculatory dysfunction. Material and Methods: Isolated organ bath studies were performed on prostatic parts of VD obtained from adult male Balb/c mice. The effect of ATX (10-6, 10-5, 3x10-5 and 10-4 M) on KCl (80 mM)-, phenylephrine (PhE, 3x10-4 M)-, adenosine 5'-triphosphate (ATP, 10-2 M)- and electrical field stimulation (EFS; 100 V, 64 Hz)-induced contractions of VD strips were evaluated in concentration dependent manner. Results: ATX at 10-6 and 10-5 did not alter the contractile responses (p > 0.05), however, higher concentrations of ATX (3x10-5 or 10-4 M) significantly inhibited the KCl-, PhE-, ATP- and EFSinduced contractions of VD strips (p < 0.05). Conclusion: The present study demonstrated for the first time that ATX decreased the contractile responses of mouse isolated VD concentration-dependently. Our results suggest that ejaculatory dysfunction might be related to the inhibitory effect of ATX on VD. [ABSTRACT FROM AUTHOR]

Abstract Background Resistance acquired after radiotherapy is directly related to the failure of various cancer treatments, including GBM. Because the mechanism for overcoming radioresistance has not yet been clearly identified, the development of diagnostic and therapeutic markers to treat radioresistance is necessary. Since increased expression of stemness- and EMT-related markers are reported to be closely correlated with radioresistance, research is underway to develop new drugs targeting these factors. Methods To develop an anticancer drug that overcomes radioresistance, a library of drugs already approved by the FDA was used. After treating radioresistant GBM cells with each drug, the expression of stemness- and EMT-related markers was confirmed by qRT-PCR, and as a result, Atomoxetine (ATX) was selected. It was confirmed that radioresistance-induced cell migratory, invasive, sphere formation abilities, and tumor growth using a xenograft mouse model were suppressed upon ATX treatment. Using a miRNA prediction tool, we discovered miR-520d-5p, which targets Notch2 and Hey1, key factors in radioresistance, and discovered circATIC targeting this miRNA, revealing its relationship with ATX. We demonstrated the expression regulation mechanism and signaling mechanism between circATIC, miR-520d-5p, Notch2, and Hey1 factors using a luciferase reporter assay. In addition, the results at the cellular level were clinically verified by confirming the correlation between radiation, miR-520d-5p, and circATIC using patient plasma by qRT-PCR. Results ATX showed potential as a treatment for radioresistance by suppressing the malignant phenotype by regulating the circATIC/miR-520d-5p/Notch2-Hey1 signaling mechanism in vitro and in vivo using radioresistant GBM cells. Conclusions This study revealed that ATX suppresses radioresistance through the circATIC/miR-520d-5p/Notch2-Hey1 signaling pathway. These results showed the potential of ATX as a new drug that can overcome radioresistance, a major challenge in cancer treatment, and the signaling factors identified in this mechanism suggest the possibility of use as potential targets for the diagnosis and treatment of radioresistance.

ObjectiveTo explore the impact of sluggish cognitive tempo (SCT) on the efficacy of atomoxetine in the treatment of attention-deficit/hyperactivity disorder (ADHD). MethodsA prospective study was conducted. Pediatric patients aged 6-12 years with a diagnosis of ADHD were selected from the Department of Psychiatry, Xijing Hospital, Air Force Military Medical University from May 2020 to May 2023. All the patients were treated with atomoxetine for 8 weeks. ADHD symptoms and SCT symptoms were assessed by Swanson, Nolan, and Pelham-Ⅳ rating scale (SNAP-Ⅳ) and SCT rating scale at baseline (before treatment), 4 weeks and 8 weeks after treatment. Pearson correlation analysis was used to analyze the correlation between SCT and SNAP-Ⅳ scores. ResultsA total of 61 pediatric patients were enrolled, including 10 cases of inattentive type and 51 cases of mixed type. Baseline SCT score was positively correlated with baseline SNAP-Ⅳ score (r＝0.490, P＜0.001) and reduction rate of SNAP-Ⅳ score at week 8 (r＝0.670, P＜0.001). The total SCT score at week 8 was positively correlated with total SNAP-Ⅳ score at baseline (r＝0.320, P＝0.012). The baseline SCT score of patients with mixed type was positively correlated with reduction rate of SNAP-Ⅳ score at week 8 (r＝0.578, P＜0.001). ConclusionsThe severity of SCT symptoms is positively correlated with the SNAP-Ⅳ reduction rate 8 weeks after atomoxetine treatment, which could be a predictor of the efficacy of atomoxetine.

The five‐choice serial reaction time task (5CSRTT) is a test of attention that provides a well‐validated ancillary measure of impulsive action, measured by premature responses. The task has been adapted for mice in touchscreen operant boxes, which is thought to offer improved test–retest reliability. Few studies have assessed the long‐term stability of performance, including premature responding in this version of the task. We used the touchscreen 5CSRTT to conduct longitudinal testing of stability of premature responding following repeated behavioral and pharmacological manipulations. Male C57BL/6J mice were trained on a baseline version of the 5CSRTT. They were then tested on versions of the task in which the stimulus duration was reduced, and inter‐trial intervals were elongated or varied within‐session. Premature responding was subsequently tested following administration of pharmacological agents known to bi‐directionally affect attention and impulsive action—cocaine, atomoxetine, and yohimbine. Mice were lastly re‐tested 6 months later using the 5CSRTT with elongated inter‐trial intervals. A reduced stimulus duration impacted attention, with reduced accuracy and increased omissions, but had no effect on premature responding. Both elongating and varying the inter‐trial interval within‐session increased premature responses. Mice showed similar and stable levels of increased premature responding 6 months later. Cocaine increased premature responding, though less than previously reported in rats. Atomoxetine reduced premature responding. Yohimbine had no effect on premature responding in the baseline task but decreased premature responding when tested using an elongated inter‐trial interval. Overall, these results highlight that the touch screen adaptation of the 5CSRTT is an effective method for longitudinal testing of attention and impulsive action and remains sensitive to performance changes arising from repeated pharmacological and behavioral challenges. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the variables that may affect treatment continuation in children aged 6 to 12 years who were newly diagnosed with ADHD. Methods: A total of 132 children diagnosed with ADHD and their parents participated in the study. Sociodemographic and clinical risk factors affecting continuation of treatment were examined using logistic regression analysis. Results: Multiple model examination revealed that greater age increased the risk of treatment discontinuation 1.824 times (p =.003) while a lower total length of paternal education increased the risk of discontinuation (1/0.835) 1.198 times (p =.022). Other variables emerging as significant in the univariate model lost that significance in the multiple model. Conclusions: Understanding the variables associated with medication discontinuation in ADHD in different populations and taking these variables into account in the development of health policies, will be useful in improving the long-term devastating effects of the disorder. [ABSTRACT FROM AUTHOR]

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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder is a childhood-onset neurodevelopmental disorder that frequently persists into adulthood with 3% of adult women having a diagnosis of attention-deficit/hyperactivity disorder. Many women are diagnosed and treated during their reproductive years, which leads to management implications during pregnancy and the postpartum period. We know from clinical practice that attention-deficit/hyperactivity disorder symptoms frequently become challenging to manage during the perinatal period and require additional support and attention. There is often uncertainty among healthcare providers about the management of attention-deficit/hyperactivity disorder in the perinatal period, particularly the safety of pharmacotherapy for the developing fetus. This guideline is focused on best practices in managing attention-deficit/hyperactivity disorder in the perinatal period. We recommend (1) mitigating the risks associated with attention-deficit/hyperactivity disorder that worsen during the perinatal period via individualized treatment planning; (2) providing psychoeducation, self-management strategies or coaching, and psychotherapies; and, for those with moderate or severe attention-deficit/hyperactivity disorder, (3) considering pharmacotherapy for attention-deficit/hyperactivity disorder, which largely has reassuring safety data. Specifically, providers should work collaboratively with patients and their support networks to balance the risks of perinatal attention-deficit/hyperactivity disorder medication with the risks of inadequately treated attention-deficit/hyperactivity disorder during pregnancy. The risks and impacts of attention-deficit/hyperactivity disorder in pregnancy can be successfully managed through preconception counselling and appropriate perinatal planning, management, and support. [Display omitted] [ABSTRACT FROM AUTHOR]

Children and adolescents with attention deficit hyperactivity disorder (ADHD) are at an increased risk of accidents and injuries, and ADHD medication has been shown to mitigate this risk in these populations. However, the injury risk and the influence of ADHD medication in adults with ADHD remain unclear. This study aimed to investigate the injury risk in adults with ADHD and assess the impact of ADHD medication on this risk. Using a nationwide health claims database, we identified 9,417 adult patients with ADHD aged 19–44 years between 2017 and 2018. A retrospective propensity score-matched case-control study was conducted to examine the association between adult ADHD and injury risk across various categories. The effects of two commonly prescribed ADHD medications, methylphenidate and atomoxetine, were evaluated using a Cox proportional hazards model. The results showed that adults with ADHD had an increased risk of sustaining various types of injuries. Methylphenidate demonstrated a protective effect against injury, which persisted after adjusting for potential confounding factors. Similarly, atomoxetine significantly reduced the injury risk. These findings underscore the importance of injury prevention strategies in adults with ADHD and highlight the substantial health benefits of ADHD medications in this population.

Non-stimulant atomoxetine is recognized in various current clinical guidelines as an important alternative to stimulants for the pharmacological treatment of attention deficit/hyperactivity disorder (ADHD) in children. While its efficacy and tolerability for core symptoms are established, there is considerable inter-individual variability in response and exposure, highlighting the need for personalized dosing. In this review, we evaluated existing studies and summarized comprehensive evidence supporting the clinical implementation of therapeutic drug monitoring (TDM) and personalized dosing of atomoxetine, organized around a series of logically structured questions. Although there are notable gaps in achieving personalized dosing across multiple critical elements, the available evidence is helpful to endorse personalized dose adjustments based on TDM and CYP2D6 genotyping “whenever possible.” We advocate for ongoing improvement and enhancement in clinical practice. Future advancements will rely on a deeper understanding of ADHD, facilitating more precise diagnoses and personalized treatment strategies.

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. [ABSTRACT FROM AUTHOR]

This article provides a review of scientific publications addressing studies of the features of the clinical picture and dynamics of the main symptoms in adult patients with attention deficit hyperactivity disorder (ADHD) and analyzes current data on the prevalence of this disorder, its leading clinical manifestations, and the most common comorbid pathologies. Research data on the impact of ADHD in adulthood on educational and professional activities are presented and the economic and criminological aspects of ADHD are considered. The main methods of psychotherapeutic correction and pharmacological therapy are discussed. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder characterized by impairing inattention and/or hyperactivity and impulsivity in children and adults. Although medications have been available to treat ADHD symptoms for decades, many are stimulant formulations. Stimulants, such as amphetamine and methylphenidate, are available in more than two dozen formulations, but all have similar adverse effects and carry a risk of misuse and dependence. In the United States (US), several nonstimulants are available to treat ADHD. Two, including atomoxetine and viloxazine extended-release (ER), are approved by the Food and Drug Administration for the treatment of ADHD in children and adults. Two others, clonidine ER and guanfacine ER, are only approved for children and adolescents in the US. Several other compounds are under investigation. Drugs in Phase 3 trials include centanafadine, solriamfetol, and L-threonic acid magnesium salt. Efficacy and safety data for nonstimulants is presented. Although many effective formulations for the treatment of ADHD are available, more than 33% of children and 50% of adults discontinue treatment during the first year. The lack of individual drug response and tolerability are reasons many stop treatment. The development of new nonstimulants may offer hope for patients who need medication alternatives. [ABSTRACT FROM AUTHOR]

Atomoxetine (ATX) is a non‐stimulant used to treat attention‐deficit/hyperactivity disorder (ADHD) and systemic exposure is highly variable due to polymorphic cytochrome P450 2D6 (CYP2D6) activity. The objective of this study was to characterize the time course of ATX and metabolites (4‐hydroxyatomoxetine (4‐OH); N‐desmethylatomoxetine (NDA); and 2‐carboxymethylatomoxetine (2‐COOH)) exposure following oral ATX dosing in children with ADHD to support individualized dosing. A nonlinear mixed‐effect modeling approach was used to analyze ATX, 4‐OH, and NDA plasma and urine, and 2‐COOH urine profiles obtained over 24–72 hours from children with ADHD (n = 23) following a single oral ATX dose. Demographics and CYP2D6 activity score (AS) were evaluated as covariates. Simulations were performed to explore the ATX dosing in subjects with various CYP2D6 AS. A simultaneous pharmacokinetic modeling approach was used in which a model for ATX, 4‐OH, and NDA in plasma and urine, and 2‐COOH in urine was developed. Plasma ATX, 4‐OH, and NDA were modeled using two‐compartment models with first‐order elimination. CYP2D6 AS was a significant determinant of ATX apparent oral clearance (CL/F), fraction metabolized to 4‐OH, and systemic exposure of NDA. CL/F of ATX varied almost 7‐fold across the CYP2D6 AS groups: AS 2: 20.02 L/hour; AS 1: 19.00 L/hour; AS 0.5: 7.47 L/hour; and AS 0: 3.10 L/hour. The developed model closely captures observed ATX, 4‐OH, and NDA plasma and urine, and 2‐COOH urine profiles. Application of the model shows the potential for AS‐based dosing recommendations for improved individualized dosing. [ABSTRACT FROM AUTHOR]

The rapid serial visual presentation (RSVP) task and continuous performance tasks (CPT) are used to assess attentional impairments in patients with psychiatric and neurological conditions. This study developed a novel touchscreen task for rats based on the structure of a human RSVP task and used pharmacological manipulations to investigate their effects on different performance measures. Normal animals were trained to respond to a target image and withhold responding to distractor images presented within a continuous sequence. In a second version of the task, a false-alarm image was included, so performance could be assessed relative to two types of nontarget distractors. The effects of acute administration of stimulant and nonstimulant treatments for ADHD (amphetamine and atomoxetine) were tested in both tasks. Methylphenidate, ketamine, and nicotine were tested in the first task only. Amphetamine made animals more impulsive and decreased overall accuracy but increased accuracy when the target was presented early in the image sequence. Atomoxetine improved accuracy overall with a specific reduction in false-alarm responses and a shift in the attentional curve reflecting improved accuracy for targets later in the image sequence. However, atomoxetine also slowed responding and increased omissions. Ketamine, nicotine, and methylphenidate had no specific effects at the doses tested. These results suggest that stimulant versus nonstimulant treatments have different effects on attention and impulsive behaviour in this rat version of an RSVP task. These results also suggest that RSVP-like tasks have the potential to be used to study attention in rodents. [ABSTRACT FROM AUTHOR]

Purpose of Research: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most frequently diagnosed neurodevelopmental disorders. It is estimated to occur in approximately 5-10% of children and adolescents. This paper aims to highlight the challenges faced by individuals suffering from ADHD, present risk factors, summarize current treatment methods, and outline the consequences of neglecting treatment. Methods: Databases such as PubMed, Medline, and ResearchGate were used. Basic Results: The goal of ADHD treatment is to reduce the severity of symptoms and improve the social, academic, and emotional functioning of children and adolescents. The choice of treatment and the selection of a specific medication depend on the patient's age and coexisting disorders. Conclusions: ADHD often coexists with other mental disorders, complicating diagnosis and treatment. Lack of or ineffective treatment has consequences such as learning difficulties, disruptions in peer and family relationships. It correlates with higher rates of traffic accidents, accidental injuries, earlier onset, and higher rates of substance abuse.

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.

Introduction: Regular cocaine use has been associated with hormonal dysfunction including hypogonadism, which can lead to fatigue, reduced stamina, sexual dysfunction, and impaired quality of life. However, cocaine's endocrine effects are largely under-reported in the scientific addiction literature and, in many cases, are not addressed within treatment services. The low profile of these adverse effects might be attributable to a lack of awareness and linkage with cocaine use, such that they are recognized only when an acute/emergency problem arises. Methods: We assessed endocrine diurnal function (adrenocorticotrophic hormone [ACTH], cortisol, and testosterone) in 26 healthy and 27 cocaine-dependent men and examined changes in hormone levels in response to a single 40 mg dose of the noradrenaline re-uptake inhibitor atomoxetine in a double-blind, placebo-controlled experimental medicine study. Results: When compared with healthy controls, diurnal and atomoxetine-induced changes in ACTH and cortisol showed greater variability in cocaine-dependent men. Interestingly, despite an exaggerated rise in ACTH following atomoxetine, an attenuated cortisol response was observed, and one-third of cocaine-dependent men had subnormal testosterone levels. Conclusion: Our findings point to a potential disconnection between the pituitary and adrenal responses in cocaine-dependent men, a higher rate of hypogonadism, and a pressing need for more research into the endocrine effects of cocaine and their clinical implications. [ABSTRACT FROM AUTHOR]

Background and Objective: Methylphenidate (MPH) and atomoxetine (ATX) are the most common medications used to treat attention-deficit hyperactivity disorder (ADHD) in China; however, despite this, there is still a paucity of studies comparing their efficacy and safety, particularly for different characteristics. To address the lack of research, a real-world prospective cohort study was conducted to examine these properties of MPH and ATX, and to analyze correlations associated with age, sex, and different ADHD presentation. Methods: Children with ADHD meeting the eligibility criteria were recruited from January 2016 to July 2021. Study participants were treated with either MPH or ATX prescribed in the real-world setting, and were followed up for 26 weeks. Clinical efficacy response and adverse events (AEs) were recorded and measured. Subgroup analysis was performed to examine the efficacy response and AEs associated with age, sex, and different ADHD presentation. Results: A total of 1050 children were recruited and 29 children were lost to follow-up. Of the 1021 children remaining, 533 were treated with MPH and 488 were treated with ATX. No significant differences were found in intelligence quotient, age, sex, or ADHD presentation between the MPH- and ATX-treated groups (p > 0.05). The response rates were 84.6% in the MPH-treated group and 63.3% in the ATX-treated group. Subgroup analysis of response rate demonstrated that the treatment effect of MPH over ATX was consistent across subgroups except in the girls (odds ratio [OR] 2.09, 95% confidence interval [CI] 0.97–4.7) and the hyperactive/impulsive presentation group (OR 2.88, 95% CI 0.77–12.76). A total of 47.8% of children experienced AEs during MPH treatment, significantly lower than the rate of 56.8% during ATX treatment (p < 0.05). The incidence of AEs in the MPH-treated group was higher in young children (<8 years: 56.8%; 8–10 years: 47.2%) and lower in children over 10 years of age (29.0%). Conclusions: Overall, MPH was more effective and better tolerated than ATX. The incidence of AEs in children treated with MPH varied with age, and was higher in young children and lower in children over 10 years of age. [ABSTRACT FROM AUTHOR]

Rationale: Atypical attention orienting has been associated with some autistic symptoms, but the neural mechanisms remain unclear. The human Posner task, a classic attention orienting paradigm, was recently adapted for use with mice, supporting the investigation of the neurobiological underpinnings of atypical attention orienting in preclinical mouse models. Objective: The current study tested mice expressing the autism-associated R451C gene mutation in neuroligin-3 (NL3) on the mouse-Posner (mPosner) task. Methods: NL3R451C and wild-type (WT) mice were trained to respond to a validly or invalidly cued target on a touchscreen. The cue was a peripheral non-predictive flash in the exogenous task and a central spatially predictive image in the endogenous task. The effects of dopaminergic- and noradrenergic-modulating drugs, methylphenidate and atomoxetine, on task performance were assessed. Results: In both tasks, mice were quicker and more accurate in the validly versus invalidly cued trials, consistent with results in the human Posner task. NL3R451C and WT mice showed similar response times and accuracy but responded differently when treated with methylphenidate and atomoxetine. Methylphenidate impaired exogenous attention disengagement in NL3R451C mice but did not significantly affect WT mice. Atomoxetine impaired endogenous orienting in WT mice but did not significantly affect NL3R451C mice. Conclusions: NL3R451C mice demonstrated intact attention orienting but altered responses to the pharmacological manipulation of the dopaminergic and noradrenergic networks. These findings expand our understanding of the NL3R451C mutation by suggesting that this mutation may lead to selective alterations in attentional processes. [ABSTRACT FROM AUTHOR]

Background: Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine. Aims: To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before. Method: This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year. Results: Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24–0.54; P < 0.0001). Conclusions: These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Aripiprazole, risperidone, atomoxetine, and methylphenidate are drugs commonly prescribed for many psychiatric conditions and can be used alone or in combination in children and adolescents. This study aimed to investigate comparatively the possible genotoxic effects or genoprotective potentials of these drugs on human lymphocytes and HepG2 cells. MATERIALS AND METHODS: Cytotoxicity analysis was performed with the cell viability test on human lymphocytes and HepG2 cells, and half-maximal inhibitory concentration (IC50) values of the drugs were determined, and three different doses (1/4 IC50, 1/2 IC50, and IC50) were applied for genetic analysis. For the determined doses, cells with and without DNA damage were examined by comet analysis. RESULTS: In lymphocytes, aripiprazole and risperidone increased DNA damage at moderate and maximum doses, whereas atomoxetine increased DNA damage only at the maximum dose. In HepG2 cells, risperidone reduced DNA damage at all doses, while atomoxetine increased DNA damage at all doses. On the other hand, in the DNA-damaged cells induced by hydrogen peroxide (H2O2), DNA damage decreased at all concentrations of all drugs in both lymphocytes and HepG2 cells. CONCLUSIONS: As a result, the genotoxicity of the drugs was found to be dose-dependent, and all drugs showed a genoprotective effect on DNA-damaged cells. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to meta-analytically estimate the dose-response relationship of atomoxetine for treating children with ADHD. Methods: We systematically searched double-blind randomized placebo-controlled trials that evaluated the effectiveness of atomoxetine for treating ADHD in children. The search was carried out in PubMed, Cochrane Library, CINHAL, and ClinicalTrials.gov databases, covering articles from their inception until January 20, 2023. In addition, a dose-response meta-analysis was conducted. Results: In this dose-response meta-analysis, 12 double-blind randomized placebo-controlled trials involving 2,250 patients were included. The efficacy of atomoxetine increased up to a dosage of 1.4 mg/kg, after which it reached a plateau. Conclusions: The first dose-response meta-analysis of atomoxetine dosing for children with ADHD conducted here enhances the robustness of the Food and Drug Administration and the European Medicines Agency dose recommendations. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between atomoxetine or methylphenidate use and arrhythmia, heart failure (HF), stroke, and myocardial infarction (MI) in attention-deficit/hyperactivity disorder (ADHD) patients mainly focused on the people of working age. Methods: In a self-controlled case series study using a Japanese claims database, we identified events of arrhythmia, HF, stroke, and MI among 15,472 atomoxetine new users and 12,059 methylphenidate new users. Adjusted incidence rate ratios (aIRRs) of outcome events were estimated using multivariable conditional Poisson regression. Results: An increased risk of arrhythmia was observed during the first 7 days after the initial atomoxetine exposure (aIRR 6.22, 95% CI [1.90, 20.35]) and in the subsequent exposure (3.23, [1.58, 6.64]). No association was found between methylphenidate exposure and arrhythmia, nor between atomoxetine or methylphenidate exposure and HF. The limited number of stroke and MI cases prevented thorough analysis. Conclusions: Clinicians should consider monitoring for arrhythmia after patients initiating or re-initiating atomoxetine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

we aimed to compare the effects of atomoxetine and trazodone (A-T) in combination with placebo in patients with obstructive sleep apnea (OSA). This randomized, placebo-controlled, double-blind, crossover trial study was conducted in adults with OSA referred to a Sleep Clinic. Participants with eligibility criteria were recruited. Patients were studied on two separate nights with one-week intervals, once treated with trazodone (50 mg) and atomoxetine (80 mg) combination and then with a placebo and the following polysomnography tests. A total of 18 patients with OSA completed the study protocol, 9(50%) were male, the mean age was 47.5 years (SD = 9.8) and the mean Body mass index of participants was 28.4 kg/m2 (SD = 3.4). Compared with the placebo, the A-T combination resulted in significant differences in AHI (28.3(A-T) vs. 42.7 (placebo), p = 0.025), duration of the REM stage (1.3%TST (A-T) vs. 13.1%TST (placebo), p = 0.001), and the number of REM cycles (0.8 (A-T) vs. 4.7 (placebo), p = 0.001), number of apneas (38.3 (A-T) vs. 79.3 (placebo), p = 0.011), number of obstructive apneas (37.2 (A-T) vs. 75.2 (placebo), p = 0.011), oxygen desaturation index (29.5 (A-T) vs. 42.3 (placebo), p = 0.022) and number of respiratory arousals (43.2 (A-T) vs. 68.5 (placebo), p = 0.048). This decrement effect did not change among those with a low-arousal phenotype of OSA. The A-T combination significantly improved respiratory events' indices compared with placebo in patients with OSA. This combination is recommended to be assessed in a large trial. It could be an alternative for those who do not adhere to the standard available treatments for OSA. • Obstructive sleep apnea severity decreased significantly after the administration of Atomoxetine and Trazodone. • Respiratory and hypoxia indices improved with pharmacological intervention. • Apnea hypopnea index decreased after administration of Atomoxetine and Trazodone combination. • Pharmacologic treatment could be a good alternative for patients with low adherence or no access to standard OSA management. [ABSTRACT FROM AUTHOR]

A cost-effective and innovative reverse phase high performance liquid chromatography (RPHPLC) technique has been devised to accurately and precisely measure the quantity of Atomoxetine Hydrochloride in both large quantities and solid dosage forms. The separation process was conducted using an Xterra RP 18 column with dimensions of 250 mm × 4.6 mm and a particle size of 5 μ. The experiment used the isocratic technique, with a mobile phase consisting of a 70:30 (v/v) mixture of water and methanol. The mobile phase was injected into the column using a pump, with a flow rate of 1.0 mL min-1. The eluent from the column was detected using a UV detector set to operate at a wavelength of 280 nm. The experiment had a duration of 5 minutes, during which the column was consistently kept at the ambient temperature. The determined retention time for Atomoxetine Hydrochloride was 3.08 minutes. The standard curves exhibited a linear relationship throughout the concentration range of 02-10 μg/ml, with a high coefficient of determination (R2 = 0.9997). The study resulted in a variety of percentage recoveries, ranging from 99% to 101%. Moreover, the Relative Standard Deviation (RSD) was computed to be 0.290%. The measured percentage composition of a commercially available formulation of Atomoxetine Hydrochloride was determined to be 100.18%. The approach was verified in accordance with the requirements set out by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The suggested RP-HPLC technique has been validated via research, showcasing its characteristics of simplicity, specificity, speed, reliability, and uniformity. Therefore, the approach suggested in this study may be used for the regular analysis of Atomoxetine Hydrochloride in both its concentrated and solid states, specifically with the aim of assuring quality control. [ABSTRACT FROM AUTHOR]

• Refractory hypotension is common in critically ill patients. • Intravenous vasoactive medications limit discharge from the intensive care unit. • Oral vasoactive medication could facilitate weaning of these medications. • Midodrine has limited supporting evidence for intravenous vasopressor liberation. • Droxidopa or atomoxetine may be options in critically ill patients with hypotension. To evaluate the effects of droxidopa or atomoxetine on intravenous (IV) vasoactive agent discontinuation in cardiothoracic intensive care unit (ICU) patients with hypotension refractory to midodrine. Single-center, retrospective cohort study. Tertiary- and quaternary-care university teaching hospital. Included patients who received at least 4 consecutive doses of droxidopa or atomoxetine and remained on concurrent midodrine. Patients were excluded if they received study medication before admission, had clinical deterioration after study medication initiation requiring additional vasoactives/escalation of IV vasoactive dosage for at least 12 hours, had a diagnosis of hepatorenal syndrome, were prisoners, or were pregnant. Droxidopa, atomoxetine, or both. The primary endpoint was time to discontinuation of IV vasoactive agents after initiation of study medication, analyzed using a Kaplan–Meier estimate with the Wilcoxon method, censoring death within 24 hours of the last dose of study medication. No adjustment for repetitive analyses was made, as the analysis was hypothesis-generating. Of the 72 charts reviewed, 45 patients met inclusion criteria (18 atomoxetine, 17 droxidopa, and 10 both). There were no differences in median time to discontinuation of IV vasoactive agents (21.9 days v 8.0 days v 13.9 days, respectively; p = 0.259) or ICU or hospital length of stay between groups. A higher percentage of patients who survived to hospital discharge received both study medications or droxidopa alone (90% v 76.5%) than atomoxetine alone (44.4%, p = 0.028). Droxidopa and atomoxetine are oral vasoactive agents with potential mechanisms to facilitate IV vasopressor weaning for patients in the ICU with hypotension refractory to midodrine, but further prospective research is needed. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Faculty of Pharmacy of Ankara University / Ankara Üniversitesi Eczacilik Fakültesi Dergisi is the property of Ankara University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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.

Abstract The psychoanaleptic medication atomoxetine (ATX) is prescribed to cure attention-deficit hyperactivity syndrome. ATX works by selective prevention of norepinephrine reuptake. It acts by raising the brain’s natural level of norepinephrine, which is necessary for behavior regulation. In this study, a sensitive and practical experimental method was employed to analyze the presence of ATX. The approach utilized a green chemistry-compatible technique, known as a one-pot experiment. The main principle behind this method was the use of molecular-size-dependant resonance Rayleigh scattering (RRS) phenomenon, which occurred due to the interaction between the dual complex of Cilefa Pink B and ATX. When ATX medication and Cilefa Pink B were combined in an acidic environment, they formed an association complex, leading to an amplification of the RRS signal. This amplification directly correlated with the concentration of ATX, specifically within the range of 40-1250 ng/mL. The RRS signal was monitored at a wavelength of 352 nm. The sensitivity of the method was demonstrated by the determination of the limit of detection (LOD) at 12.9 ng/mL and the limit of quantitation (LOQ) at 39.2 ng/mL. The variables of the method were thoroughly investigated and optimized. To ensure the reliability of the method, it was validated according to the International Council for Harmonisation (ICH) guidelines. Furthermore, the method was successfully applied to analyze ATX in its prescribed dosage form. The achievement of using the established resonance Rayleigh scattering (RRS) technology to analyze the target drug in plasma and ensure content uniformity was a remarkable feat.

The psychoanaleptic medication atomoxetine (ATX) is prescribed to cure attention-deficit hyperactivity syndrome. ATX works by selective prevention of norepinephrine reuptake. It acts by raising the brain's natural level of norepinephrine, which is necessary for behavior regulation. In this study, a sensitive and practical experimental method was employed to analyze the presence of ATX. The approach utilized a green chemistry-compatible technique, known as a one-pot experiment. The main principle behind this method was the use of molecular-size-dependant resonance Rayleigh scattering (RRS) phenomenon, which occurred due to the interaction between the dual complex of Cilefa Pink B and ATX. When ATX medication and Cilefa Pink B were combined in an acidic environment, they formed an association complex, leading to an amplification of the RRS signal. This amplification directly correlated with the concentration of ATX, specifically within the range of 40-1250 ng/mL. The RRS signal was monitored at a wavelength of 352 nm. The sensitivity of the method was demonstrated by the determination of the limit of detection (LOD) at 12.9 ng/mL and the limit of quantitation (LOQ) at 39.2 ng/mL. The variables of the method were thoroughly investigated and optimized. To ensure the reliability of the method, it was validated according to the International Council for Harmonisation (ICH) guidelines. Furthermore, the method was successfully applied to analyze ATX in its prescribed dosage form. The achievement of using the established resonance Rayleigh scattering (RRS) technology to analyze the target drug in plasma and ensure content uniformity was a remarkable feat. [ABSTRACT FROM AUTHOR]

Objectives: A simple, sensitive, selective, and cost-effective colorimetric method has been established for the quantitative estimation of atomoxetine hydrochloride in bulk and formulation. Materials and Methods: It was established based on the visible reaction between atomoxetine hydrochloride and 1,2-naphthoquinone-4-sulfonic acid sodium salt in a basic medium (potassium hydroxide). The resulting orange colored chromogen exhibited an absorption maximum at 474 nm. Results: Based on the optimization studies, distilled water as the solvent, 1% w/v potassium hydroxide (2 mL), and 0.3% w/v 1,2-naphthoquinone-4-sulfonic acid sodium salt (2 mL) were used in the method. The developed method was validated per the International Council for Harmonization (ICH) guidelines. The linearity was found at a concentration of 10-50 µg/mL. The method showed a good correlation between the concentration of atomoxetine hydrochloride and its absorbance. The correlation coefficient (r2) of 0.999 evidenced the same. The limits of detection and quantification were 0.20 and 0.606 µg/mL, respectively, for atomoxetine hydrochloride. The accuracy and precision of the method were also evaluated and the results obtained were within the acceptance criteria (relative standard deviation % < 2.00). The percentage assay of atomoxetine hydrochloride proved to be 101.52, which is in accordance with its label claim. Conclusion: The developed method is non-complex and can be effectively employed in the analytical practices of atomoxetine hydrochloride in pharmaceutical dosage forms. [ABSTRACT FROM AUTHOR]

Research Question and Objective: While the number of pharmacoepidemiological studies on stimulant-based ADHD medications has expanded rapidly in recent years, likely due to the stimulant shortage, few studies have analyzed non-stimulant ADHD medications from a pharmacoepidemiological perspective. Such research is important because a significant number of individuals with ADHD have medical or psychiatric conditions that preclude stimulant use. Furthermore, no studies, to our knowledge, have analyzed atomoxetine exchanges on the black market. In this report, we seek to fill both these gaps in the research by analyzing black market diversions of atomoxetine, a non-stimulant medication for ADHD. As ADHD medication diversion is a growing issue, we also hypothesize the pharmacoepidemiologic contributors to and implications of such diversion. Method: This study analyzed black market atomoxetine purchases entered on the web-based platform StreetRx between January 2015 and July 2019. Data included the generic drug name, dosage, purchase price, date, and location in the United States. The mean price per milligram was determined and a heatmap was generated. Results: The average price per milligram of 113 diverted atomoxetine submissions was USD 1.35 (±USD 2.76 SD) (Median = USD 0.05, Min = USD 0.01, Max = USD 20.00). The states with the most submissions included Michigan (11), Pennsylvania (9), Indiana (8), and Ohio (8). Conclusion: The cost per milligram of atomoxetine on the black market is over 50 times the cost per milligram of the generic prescribed form. Future qualitative studies should investigate reasons why individuals are motivated to purchase atomoxetine, a non-stimulant medication, on the black market (recreational vs. nootropic vs. other clinical uses). [ABSTRACT FROM AUTHOR]

We have examined the effect of atomoxetine and Xiaoer Huanglong granules combined with psycho-behavioral modification therapy on attention-deficit/hyperactivity disorder children. Children diagnosed with attention-deficit/hyperactivity disorder were treated with atomoxetine + Xiaoer Huanglong granules (control group) or atomoxetine + Xiaoer Huanglong granules and received psycho-behavioral modification therapy (treatment group). The results show that the treatment group presented a higher overall response rate and a shorter duration of hyperactivity, inattention, and emotional instability than the control group (P < 0.05). After treatment, higher correct scores and serum levels of glial cell line-derived neurotrophic factor, lower error scores and error rate, as well as lower Abbreviated Symptom Questionnaire and Swanson, Nolan, and Pelham, version IV Scale scores, were observed in the treatment group (P < 0.05). Moreover, the incidence of adverse reactions in both groups was similar (P > 0.05). To sum up, atomoxetine, Xiaoer Huanglong granules, and psycho-behavioral modification therapy can effectively improve the learning concentration of attention-deficit/hyperactivity disorder children. [ABSTRACT FROM AUTHOR]

An unknown impurity was identified using the HPLC technique at relative retention time ~1.07 with a peak area of 0.45% during the commercial synthesis of atomoxetine. The profile of the new impurity was established using 1H NMR and LCMS spectroscopy and found to be N,N-dimethyl-3-phenyl-2,3-dichloropropylamine. Adetailed analysis was made using different experimental techniques to find the cause of dichloro impurity. It has been recognized that thionyl chloride (SOCl2) was the potential cause of the formation of the dichloro impurity. The mechanism of the formation of the impurity using retrosynthetic analysis and synthetic strategy was also discussed. The synthesized impurity was compared with the formed impurity by employing LCMS, IR, and NMR spectroscopy. Astrategy for minimizing this potential dichloro impurity was discussed. [ABSTRACT FROM AUTHOR]

The objective of the study was to compare the use of attention deficit hyperactivity disorder (ADHD) medication among children and adolescents in Scandinavia 2010–2020. Using aggregated prescription data for individuals aged 5–19 years, we calculated annual prevalence proportions of ADHD medication (users/1000 inhabitants) for each country, overall and stratified by age and sex. Overall, use of ADHD medication increased during 2010–2020 in all countries. The increase was pronounced in Sweden reaching 35 users/1000 inhabitants in 2020 (119% increase), whereas it reached 22/1000 in Denmark and Norway (equivalent to a 38% and 16% increase, respectively). Methylphenidate was the most frequently used drug and Sweden had the highest use reaching 25/1000 in 2020 compared to 16/1000 and 18/1000 in Denmark and Norway, respectively. Lisdexamfetamine use increased steadily and was also highest in Sweden (13/1000 in 2020). In 2020, atomoxetine use was higher in Sweden (4.6/1000) and Denmark (4.5/1000) compared to Norway (2.2/1000). From 2015, use of guanfacine increased in Sweden reaching 4.4/1000 in 2020 but remained low in Denmark (0.4/1000) and Norway (0.7/1000). Use of dexamphetamine was low (ranging from 0.47 to 0.75/1000 in 2020) in the three countries. ADHD medication use was highest in Sweden across all age groups. In all countries, the prevalence was higher in males compared to females. In conclusion, use of ADHD medication among children and adolescents in Scandinavia is increasing. The prevalence of use is higher in Sweden for all drug groups compared to Norway and Denmark. [ABSTRACT FROM AUTHOR]