Search Results (45)

Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental condition, and pharmacogenetic studies aim to clarify interindividual variability in treatment responses and adverse effects. Despite increasing research, the field remains fragmented. This review provides a bibliometric analysis of ADHD pharmacogenetics (2005–2025), identifying its intellectual foundations, thematic structure, and global distribution. Methods: A bibliometric search was conducted in Scopus and Web of Science, retrieving 711 documents published between 2005 and July 2025. Data were analyzed with the Bibliometrix R package and Biblioshiny interface, applying bibliometric mapping, Bradford’s Law, co-word analysis, and thematic mapping. Only peer-reviewed journal articles, books, and book chapters were included to ensure scientific rigor. Results: The dataset shows a modest annual growth rate but strong impact, with an average of 29.6 citations per article. Highly cited works converge into four domains: (i) clinical guidelines and pharmacological treatments; (ii) cognitive heterogeneity and subtypes; (iii) neurodevelopmental and genetic mechanisms; (iv) environmental and health-related influences. Geographically, the United States leads with 24.8% of publications, followed by Brazil, China, and European countries. Keyword analysis reveals two main clusters: a clinical–therapeutic pole (methylphenidate, atomoxetine, child) and a genetic–molecular pole (dopamine transporter, SNPs, genotype). Conclusions: ADHD pharmacogenetics shows consolidation with strong clinical and genetic cores but limited integration of comorbidity, adult populations, and non-stimulant treatments. Future research should prioritize multi-center cohorts, multi-omic designs, and stronger international collaboration to advance precision medicine in ADHD. Full article

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) in adults is frequently accompanied by psychiatric comorbidities that worsen outcomes and complicate treatment. Pharmacological management is central in care, yet its impact on co-occurring disorders remains uncertain. This systematic review evaluated the effectiveness of commonly prescribed medications for adult ADHD (methylphenidate, atomoxetine, bupropion, and lisdexamfetamine) on comorbid mood, anxiety, personality, and substance use disorders. Tricyclic antidepressants were also included in the search strategy; however, no eligible adult studies assessing imipramine or desipramine in patients with ADHD and psychiatric comorbidity were identified. Methods: A systematic search of the literature was conducted to identify studies examining these medications in adults with ADHD and at least one psychiatric comorbidity. Eligible studies reported clinical outcomes for both ADHD symptoms and the co-occurring disorder. Data were extracted and narratively synthesized, with particular attention paid to treatment effects and sources of heterogeneity. Results: Across the included studies, pharmacological treatments consistently improved core ADHD symptomatology. Their effects on psychiatric comorbidity were more variable. Some evidence suggested beneficial outcomes for selected anxiety disorder subtypes and for features of Cluster B personality disorders, possibly related to reductions in emotional dysregulation and impulsivity. Findings regarding substance use disorders were mixed: several studies reported reduced craving or substance use, but long-term stabilization was inconsistent. Marked heterogeneity in study design, populations, and outcome measures limited comparability. Conclusions: Current pharmacological treatments for adult ADHD show reliable efficacy for core symptoms but inconsistent benefits across comorbid psychiatric conditions. While targeted improvements may occur in specific domains, the evidence base is insufficient to define optimal long-term strategies for adults with ADHD and complex comorbidity. Rigorous, longitudinal studies are needed to clarify medication effects on distinct comorbid profiles and to inform integrated treatment planning. Full article

Background/Objectives: Interpersonal violence is an increasing public health concern, and its prediction and prevention remain global challenges. This study aimed to identify prescribed medications associated with interpersonal violence in Spain. Methods: A descriptive, longitudinal and retrospective study and case-non case study of spontaneous reports of adverse drug reactions corresponding to interpersonal violence recorded in the Spanish Pharmacovigilance Database (FEDRA^®) from 1984 to 31 March 2021. Results: 533 cases were reported in the study period. The mean age was 46.70 years with ages ranging from 1 to 99 years. There were no sex differences except in child and adolescent age group where most reports were from male. Main therapeutic groups involved were nervous system (62.3%), anti-infectives for systemic use (10%) and respiratory system (8.6%). Mostly drugs reported were montelukast, levetiracetam, bupropion, donepezil, perampanel, quetiapine, fluoxetine, and lorazepam. A statistically significant association/disproportion in the notification has been found in the reporting of interpersonal violence and different drugs according to the literature, notably atomoxetine, perampanel, memantine, donepezil, montelukast and methylphenidate. Conclusions: The results highlight that interpersonal violence, while rare, could occur as a clinically relevant adverse reaction to a small subset of medications. They underscore the importance of careful prescribing, especially in vulnerable populations and in individuals with a history of psychiatric disorders. Full article

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition frequently treated with pharmacological interventions, most commonly stimulants such as methylphenidate and amphetamines, alongside non-stimulant options. This narrative review, based on 31 publications and five national drug utilization registers, summarizes global trends in ADHD medication use since 2000. Across most countries, prevalence of ADHD medication use increased steadily, with the sole exception of the Netherlands, where recent declines were observed. The highest prevalence of ADHD medication use was consistently found among older children and adolescents. While boys showed higher values of prevalence of ADHD medication use than girls in childhood, faster increases among females resulted in reversed gender ratios in several adult populations. Methylphenidate remained the most widely prescribed drug, although the use of lisdexamfetamine and guanfacine has expanded in recent years. Variations in national guidelines, diagnostic frameworks, healthcare access, and sociocultural acceptance of pharmacotherapy contributed to observed differences across regions. Increasing use of ADHD medications raises important questions about equitable access to treatment, potential overdiagnosis, and the risk of stimulant misuse. These findings highlight the need for continued monitoring of utilization patterns to ensure safe, rational, and equitable ADHD care worldwide. Full article

Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized for its impact on social functioning, including deficits in social cognition and empathy. Emerging neurobiological evidence highlights the potential role of oxytocin in these impairments. However, the influence of pharmacotherapy, particularly methylphenidate (MPH) and atomoxetine (ATX), on these domains remains underexplored. This study aimed to examine the effects of MPH and ATX on social cognition, empathy, and serum oxytocin levels in children with ADHD. Methods: This study included 152 children aged 6–12 years diagnosed solely with ADHD. The patient group consisted of 102 children, comprising n = 52 receiving MPH and n = 50 receiving ATX for at least 3 months. The control group comprised 50 newly diagnosed, untreated children. A sociodemographic form, the Social Skills Rating Scale (SRSS), the Reading the Mind in the Eyes Test (RMET), the Bryant Empathy Index (BEI), and the Swanson, Nolan, and Pelham Questionnaire (SNAP-IV) were applied. Serum oxytocin levels were measured via venous blood samples. Results: Medicated children exhibited significantly elevated SRSS scores, irrespective of the pharmacotherapy administered. RMET scores were significantly higher in the ATX group. No significant differences were found between the three groups in terms of empathy scores and serum oxytocin levels. A significant negative correlation was identified between ADHD symptom severity and RMET and SRSS-Total scores. Regular medication use was a significant predictor of SRSS scores, while empathy and serum oxytocin levels were nonsignificant predictors. Conclusions: Pharmacotherapy may enhance social cognition among children with ADHD. Longitudinal studies are warranted to assess the long-term effects of medication on social cognition and empathy. Full article

Background: Public discourse on social media plays an increasingly influential role in shaping health-related perceptions and behaviours. Individuals share experiences, concerns, and opinions beyond clinical settings around different issues. X (formerly Twitter) provides a unique lens through which to examine how different treatments are perceived, used, and debated across diverse communities over time. Objective: The study aims to (a) identify the types of ADHD medications mentioned in posts, depending on language and user type; (b) evaluate the popularity of content related to these medications, considering language and user type; (c) analyse temporal changes in the frequency of mentions between 2006 and 2022; and (d) examine the distribution of tweets across different content categories. By addressing these objectives, this study provides insights into public perceptions of ADHD medications, which may help healthcare professionals better understand online discussions and improve their communication with patients, facilitating more informed treatment decisions. Methods: An observational study was conducted analysing 254,952 tweets in Spanish and English about ADHD medications from January 2006 to December 2022. Content analysis combined inductive and deductive approaches to develop a categorisation codebook. BERTWEET and BETO models were used for machine learning classification of English and Spanish tweets, respectively. Descriptive statistical analysis was performed. Results: Overall, stimulant medications were posted more frequently and received higher engagement than non-stimulant medications. Methylphenidate, dextroamphetamine, and atomoxetine were the most commonly mentioned medications, especially by patients, who emerged as the most active users among the English tweets. Regarding medical content, tweets in English contained more than twice the number of mentions of inappropriate use compared to those in Spanish. There was a high content of online medication requests and offers in both languages. Conclusions: In this study, conducted on X, discussions on ADHD medications highlighted concerns about misuse, adherence, and trivialisation, with clear differences between English and Spanish tweets regarding focus and type of user participation. These findings suggest that monitoring social media can provide early signals about emerging trends, helping clinicians address misconceptions during consultations and informing public health strategies aimed at the safer and more responsible use of ADHD medications. Full article

Chronic stress induces mood disturbances, disrupts gut barrier function, and promotes low-grade systemic inflammation. This study assessed the therapeutic effects of atomoxetine (ATX), escitalopram (ESC), cannabidiol (CBD), and CBD-loaded lipid nanoparticles (CBD/LNP) in male rats exposed to repeated restraint stress. Stressed rats exhibited a 2.03-fold increase in interleukin-6 and a 1.89-fold increase in TNF-α, a 1.20-fold decrease in brain-derived neurotrophic factor, a 1.36-fold decrease in osteocalcin, accompanied by alterations in gut metabolites, particularly short-chain fatty acids (SCFAs; from 155.3 to 94.83 μmol/L), polyamines (from 273.6 to 192.4 μmol/L), and bile acids (BAs; from 21.19 to 14.53 μmol/L), compared with the control group. Protein analysis revealed gut barrier disruption and microglial/macrophage activation, accompanied by reduced synaptic plasticity. ATX improved gut permeability and reduced glial activation but did not restore osteocalcin. ESC provided neuroimmune benefits with limited and BA gut restoration and modulated the gut–brain axis and improved anxiety-like behaviors, partly by altering gut microbiota and metabolites. CBD and CBD/LNP treatment restored intestinal barrier function, as indicated by intestinal permeability in the range of 1.15–1.61-fold. These treatments also normalized bile acids (1.0–1.38-fold) and osteocalcin (1.0–1.28-fold) and significantly reduced glial activation (0.63–1.12-fold) as opposed to the non-treated stressed group. All treatments were found to be effective in correcting SCFA and polyamine levels. Histological analysis confirmed that CBD/LNP, ATX, and ESC ameliorated tissue alterations. These findings highlight CBD/LNP as a promising intervention for stress-induced gut–brain–bone axis disruption, supporting its potential as a therapeutic alternative through modulation of microbiota-driven gut–brain communication in stress-associated disorders. Full article

Background/Objectives: The growing interest in personalized medicine has accelerated the exploration of three-dimensional (3D) printing technologies in pharmaceutical applications. This study investigates the potential of selective laser sintering (SLS) as a flexible, small-scale manufacturing method for atomoxetine tablets tailored for individualized therapy, comparing it with conventional direct compression. Methods: Atomoxetine tablets were produced using SLS 3D printing with varying laser scanning speeds and compared to tablets made via a compaction simulator. Formulations were based on hydroxypropyl methylcellulose (HPMC) as the primary matrix former. The physical properties, drug content, disintegration time, and dissolution profiles were evaluated. The structural and chemical integrity were assessed using SEM, FTIR, DSC, and XRPD. Results: The SLS tablets exhibited comparable mechanical properties and drug content to those made by compaction. Lower laser speeds produced harder tablets with slower disintegration, while higher speeds yielded more porous tablets with ultra-rapid drug release (>85% in 15 min). All tablets met the European Pharmacopoeia dissolution criteria. No significant drug–excipient interactions or changes in crystallinity were detected. Conclusions: SLS printing is a viable alternative to traditional tablet manufacturing, offering control over drug release profiles through parameter adjustment. The technique supports the development of high-quality, patient-specific dosage forms and shows promise for broader implementation in personalized pharmaceutical therapy. Full article

Background/Objectives: The co-occurrence of Attention-deficit/hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) is very common and worsens adaptive functioning. This systematic review evaluates both pharmacological and non-pharmacological interventions in this underserved population. Methods: Registered on PROSPERO (CRD42024526157), a systematic search was conducted on PubMed, Embase, and Web of Science until 5 April 2025. The review includes (a) pilot studies and RCTs, (b) participants aged <18 years, (c) diagnoses of ASD and ADHD based on DSM-IV/V or ICD-9/10, (d) at least one group receiving any intervention, and (e) publications in English, Italian, Spanish, or German. Newcastle Ottawa Scale tools for non-randomized studies and the Cochrane Risk of Bias Tools for randomized controlled trials were used to assess studies’ quality. Results: A total of 32 studies were included: 87.5% concerning pharmacological treatments. Specifically, methylphenidate (MPH, n = 11), atomoxetine (ATX, n = 11), guanfacina (n = 4), clonidine (n = 1), or atypical antipsychotics (n = 1) were examined. MPH and ATX were most frequently studied, with both showing positive effects in reducing ADHD core symptoms compared to placebo. ATX also reduces stereotyped behaviors and social withdrawal, although more withdrawals due to adverse events (AEs) were reported for ATX than MPH. Four studies (12.5%) examined non-pharmacological interventions, including treatment with virtual reality tools, digital platforms, educational animations, and biomedical protocols; improvements in emotion recognition, behavioral regulation, attention, and social functioning were found. Conclusions: While limited data prevent definitive conclusions, MPH and ATX appear to be relatively safe and effective on hyperactivity-impulsivity symptoms, even in individuals with ASD. Evidence on non-pharmacological treatments is limited, and further studies are needed to better establish their therapeutic potential. Full article

Background/Objectives: Sensory perception is influenced by internal neuronal variability and external noise. Neuromodulators such as norepinephrine (NE) regulate this variability by modulating excitation–inhibition balance, oscillatory dynamics, and interlaminar connectivity. While NE is known to modulate cortical gain, it remains unclear how it shapes sensory processing under noisy conditions. This study investigates how adrenergic modulation affects signal-to-noise processing and perceptual decision-making in the primary visual cortex (V1) of mice exposed to varying levels of visual noise. Methods: We performed in vivo local field potential (LFP) recordings from layers 2/3 and 4 of V1 in sedated mice to assess the impact of visual noise and systemic administration of atomoxetine, a NE reuptake inhibitor, on cortical signal processing. In a separate group of freely moving mice, we used a two-alternative forced-choice to evaluate the behavioral effects of systemic and intracortical adrenergic manipulations on visual discrimination. Results: Moderate visual noise enhanced cortical signal processing and visual choices, consistent with stochastic resonance. High noise levels impaired both. Systemic atomoxetine administration flattened the cortical signal-to-noise ratio function, suggesting disrupted gain control. Behaviorally, clonidine impaired accuracy at moderate noise levels, while atomoxetine reduced discrimination performance and increased response variability. Intracortical NE infusions produced similar effects. Conclusions: Our findings demonstrate that NE regulates the balance between signal amplification and noise suppression in a noise- and context-dependent manner. These results extend existing models of neuromodulatory function by linking interlaminar communication and cortical variability to perceptual decision-making. Full article

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that significantly impacts learning, daily functioning, and personal development. Astaxanthin (ASTA), a naturally occurring antioxidant, has garnered interest as a potential therapeutic agent for various diseases, particularly in mitigating oxidative stress. This study explores a novel application of ASTA in the context of ADHD, aiming to investigate its therapeutic effects and underlying mechanisms. Spontaneously hypertensive rats (SHRs), widely used ADHD model animals, were treated with ASTA (50/100 mg/kg/day) for three weeks, 5 mg/kg/day atomoxetine (ATO) as the positive, and Wistar Kyoto (WKY) rats as control. Behavioral improvements were assessed using the open field test (OFT) and the Morris water maze (MWM). Biochemical analyses were conducted to evaluate changes in the levels of various neurotrophic factors, while histological examinations were performed to assess neuroprotective effects. Additionally, the role of ASTA in the brain–gut axis was investigated. The behavioral symptoms of hyperactivity, anxiety, and impaired spatial memory in ADHD animals were mitigated by ASTA. This improvement is primarily attributed to the restoration of neurotransmitter levels, particularly dopamine (DA), achieved through the modulation of several critical components within the dopamine system, including dopamine receptor 1 (DR1), dopamine transporter (DAT), tyrosine hydroxylase (TH), and synaptic-associated protein 25 (SNAP-25). Additionally, regulating the serotonin transporter (SERT) and glial cell-derived neurotrophic factor (GDNF) supports the recovery of serotonin levels and facilitates optimal brain development. Furthermore, cerebellar cells were protected, and the structure of the intestinal microbiota was regulated. ASTA can mitigate ADHD symptoms in SHR through the modulation of the dopaminergic system, multiple neurotransmitters, neurotrophic factors, and the neuro-intestinal environment, which establishes ASTA as a promising nutraceutical candidate for adjunctive therapy in pediatric ADHD. Full article

Drug-induced liver injury (DILI) is one of the main causes of acute liver failure in children. Its incidence is probably underestimated, as specific diagnostic tools are currently lacking. Over 1000 known drugs cause DILI, and the list is expanding. The aim of this review is to describe DILI pathogenesis and emphasize the drugs accountable for child DILI in order to aid its recognition. Intrinsic DILI is well described in terms of mechanism, incriminated drugs, and toxic dose. Conversely, idiosyncratic DILI (iDILI) is unpredictable, occurring as a result of a particular response to drug administration, and its occurrence cannot be foreseen in clinical studies. Half of pediatric iDILI cases are linked to antibiotics, mostly amoxicillin–clavulanate, in the immune-allergic group, while autoimmune DILI is the hallmark of minocycline and nitrofurantoin. Secondly, antiepileptics are responsible for 20% of pediatric iDILI cases, children being more prone to iDILI caused by these agents than adults. A similar tendency was observed in anti-tuberculosis drugs, higher incidences being reported in children below three years old. Current data show growing cases of iDILI related to antineoplastic agents, atomoxetine, and albendazole, so that it is advisable for clinicians to maintain a high index of suspicion regarding iDILI. Full article

Objectives: The treatment of emotional dysregulation (ED) poses a major challenge for clinicians managing adult attention-deficit/hyperactivity disorder (ADHD). This naturalistic longitudinal study aimed to evaluate the effects of combining mood stabilizers (MS) with standard pharmacotherapy in this population. Methods: Fifty-six adult patients with ADHD, with or without bipolar spectrum disorders, who were followed-up for at least 4 months at Pisa University Hospital were included and grouped based on the prescription of ADHD treatment with prior MS, with conomitant MS and without MS. Changes in self-reported ED, self-reported and informant-reported ADHD severity were assessed using RIPoSt-40, ASRS-v1.1, and CAARS-O:SV. Longitudinal analyses were conducted separately for each group using a pairwise one-sample paired Student’s t-test. Results: A significant reduction in ED severity was observed in those treated with methylphenidate (MPH) and concomitant MS and in those with atomoxetine (ATX) without MS. Negative emotionality and emotional impulsivity significantly decreased in both these groups, while affective instability only improved in those with MPH and concomitant MS. Self-reported ADHD improvements were significant in all groups receiving MPH, whether with concomitant, prior, or without MS. Significant changes in informant-reported ADHD severity were found in those receiving MPH with concomitant or prior MS. Conclusions: The findings highlight the benefits of concomitant MS and MPH treatment on ED, suggest a preferential effect of ATX on negative emotionality, and confirm the effectiveness of MPH for adult ADHD symptoms, regardless of additional treatment with MS. Further studies are needed to explore whether and how MS and MPH may complement each other in reducing ED. Full article

Background/Objectives: Routine screening electrocardiograms (ECGs) prior to starting medications for attention-deficit/hyperactivity disorder (ADHD) remain controversial. This real-world study assessed corrected QT (QTc) interval data from pediatric patients who had a baseline ECG performed prior to initiating treatment with ADHD medications and ≥6 months of clinical follow-up. Methods: A retrospective chart review of children aged 2–18 years diagnosed with ADHD with/without autism spectrum disorder (ASD) at child neurology clinics in Jordan (June 2019 and June 2021) was performed, and children were prescribed with ADHD medications to manage symptoms. Patients had ≥6 months of follow-up and no known cardiac disease/family history. A baseline ECG and regular clinical exams were performed for each child. Results: Of 458 patients with baseline ECGs, 362 met the study inclusion criteria. Overall, 286 (79.0%) patients were diagnosed with ASD/comorbid ADHD and 76 (21.0%) with ADHD alone; 61 (16.9%) were prescribed atomoxetine, 38 (10.5%) methylphenidate, 134 (37.0%) risperidone, and 129 (35.6%) aripiprazole. The patients’ mean ± SD age was 6.4 ± 3.5 years, and most were male (n = 268, 74.0%). The mean baseline QTc interval was 400 ± 22 ms (median, 400 ms); one patient had a QTc interval >460 ms and was excluded from initiating treatment with any ADHD medications. During the ≥6-month follow-up, none of the patients had any signs or symptoms of adverse cardiac effects. Conclusions: Routine screening ECGs prior to treatment with ADHD medications may not be necessary in healthy children with no family history of cardiac disease. However, further studies are needed to evaluate the long-term effects of ADHD medications in low-risk pediatric patients. Full article