PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “attention-deficit hyperactivity disorder”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1992

Integrated multimodal therapy of children with attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) affects about 3-9% of children in the United States. It is a complex, multidetermined ailment that causes profound difficulty not only for the children but also for their families and those in the broader social environment (e.g., schools). Although medication helps an ADHD child's day-to-day functioning, it is less effective in producing long-lasting improvement when used alone. The author therefore discusses the rationale and techniques for multimodal treatment, including the use of education, cognitive-behavioral therapy, behavior modification, and structural and dynamic therapy, as well as medication. He emphasizes that the use of multiple modalities produces therapeutic benefit greater than the sum of each modality's contribution. The author's basic premise is that psychodynamic understanding is crucial in determining how to combine various therapies and make them mutually facilitative.

Attention Deficit Disorder with Hyperactivity↗
PubMed2025

The relationship between major depression, attention-deficit hyperactivity disorder and coronary artery disease: A two-sample Mendelian randomization analysis.

Coronary artery disease (CAD) constitutes a principal cause of global morbidity and mortality. Studies imply a connection between mental health disorders, especially major depression (MD) and attention-deficit hyperactivity disorder (ADHD), and the risk of CAD. To investigate the causal influence of genetic susceptibility to MD and attention-deficit/hyperactivity disorder (ADHD) on the risk of CAD, summary-level data from genome-wide association studies involving individuals of European descent were utilized. This analysis identified 11 single-nucleotide polymorphisms (SNPs) associated with MD, 60 SNPs linked to ADHD, and 10 SNPs related to CAD as instrumental variables. The inverse variance weighted method was employed for causal estimation, complemented by sensitivity analyses using MR-Egger regression and the weighted median estimator. A positive causal relationship was identified between MD, attention-deficit/hyperactivity disorder (ADHD), and the risk of CAD [MD: Odds Ratio (OR): 42.66, 95% Confidence Interval (CI): 7.55-241.2; ADHD: OR: 1.055, 95% CI: 1.006-1.106]. No significant causal association was observed between obesity and ADHD. In the multivariable Mendelian randomization (MVMR) analysis, the causal effect of ADHD on CAD was found to be diminished (OR: 1.005, 95% CI: 0.998-1.020), while the impact of body mass index on CAD remained stable (OR: 1.557, 95% CI: 1.459-1.661). This Mendelian randomization study reveals the lack of a consistent association among MD, ADHD, and CAD, suggesting a causal relationship and bidirectional effects between ADHD and obesity.

Humans↗
PubMed2026

Antecedents and outcomes of a later attention-deficit hyperactivity disorder (ADHD) diagnosis in females.

BACKGROUND: Females are less likely than males to be diagnosed with attention-deficit hyperactivity disorder (ADHD). When diagnosed, females are older than males. AIMS: In this study, we examined the childhood antecedents of later ADHD diagnosis and its impact on adolescent/emerging adult outcomes, with a focus on females. METHOD: In this cohort study, we used data from a Welsh nation-wide electronic cohort of 13 593 individuals (n = 2680 (19.7%) females) diagnosed with ADHD and 578 793 individuals (n = 286 734 (49.5%) females) without ADHD. We compared females with later diagnoses (ages 12-25) to those with earlier, timely diagnoses (ages 5-11) and no diagnosis, in terms of childhood (ages 5-11) antecedents and adolescent/adult (ages 12-25) outcomes. We also tested for sex differences. RESULTS: Although females with earlier ADHD diagnosis showed more health and educational difficulties in childhood than those with later diagnosed ADHD (odds ratios ranged from 0.18 to 0.92), there was clear evidence of these difficulties in females with later diagnosed ADHD, compared with females without ADHD (odds ratios: 1.07-9.02). In adolescence/early adulthood, females with later diagnosed ADHD used more healthcare services and had worse mental health, educational and socioeconomic outcomes than females diagnosed earlier (odds ratios: 1.39-4.96) and those without ADHD (odds ratios: 1.54-23.98). Many of these outcomes were exacerbated in females compared with males. CONCLUSIONS: The results demonstrate that later ADHD diagnosis is associated with significant negative outcomes by adolescence and disproportionately disadvantages females. Despite later diagnosis, there was clear evidence of childhood mental health and educational difficulties when compared with females without ADHD. Therefore, timely childhood ADHD diagnosis may help to mitigate later risks, especially for females.

Attention–deficit hyperactivity disorder↗
PubMedDate not supplied

Attention-deficit hyperactivity disorder in adults.

It has been estimated that 30% to 70% of children who are diagnosed as having attention-deficit hyperactivity disorder (ADHD) will continue to show symptoms of the condition as adults. Since the prevalence of ADHD among school children may be 3% or more, its prevalence among adults may be 1% or 2%. The third revised edition of the Diagnostic and Statistical Manual (1987) of the American Psychiatric Association lists three essential features for the diagnosis of ADHD: "developmentally inappropriate inattention, impulsiveness, and hyperactivity." Other conditions associated with ADHD in adults include learning disabilities (or their sequelae), general anxiety disorder, drug and alcohol abuse, and dysthymic and cyclothymic disorders. Strong correlations have been found between ADHD and oppositional defiant and conduct disorders in children and an increased risk for antisocial disorders in adults. A combination of genetic, biologic, and environmental factors appears to be implicated in the etiology of ADHD. The management of adult ADHD requires a multimodal approach. The patient needs to be informed of the cause of his or her impulsive and often self-destructive behavior. Many patients will have learning difficulties that require evaluation and remediation by specialists in learning disabilities. Psychotherapy can help the patients resolve disturbances in perceptions of self and others and family therapy can address difficulties in the adult's relationships with family members. Pharmacotherapy of adult ADHD includes the use of central nervous system stimulants, such as methylphenidate, dextroamphetamine, and pemoline, of the tricyclic antidepressants imipramine and desimipramine, and of other antihypertensive, analgesic, and antimanic drugs.

Adult↗
PubMed2025

Genome-wide analysis of screen behaviors among adolescents identifies novel loci and overlap with educational attainment and mental disorders.

Technological devices play a central role in adolescents' life. Despite concerns about negative effects of excessive screen time, there is little knowledge of screen behaviors' genetic architecture. Using self-reports from adolescents in the Norwegian Mother, Father, and Child Cohort Study (n = 18,490), we performed genome-wide association analysis for four screen behaviors: time spent (1) watching television; (2) gaming; (3) sitting/lying down with a screen device; and (4) using social media. The resulting summary statistics were analysed using the conditional false discovery rate (condFDR) approach to increase genetic discovery. We also estimated SNP-heritabilities of the screen behaviors and genetic correlations with eight psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, attention-deficit hyperactivity disorder, anorexia nervosa, cannabis use disorder and alcohol use disorder), and educational attainment. Screen behaviors displayed significant SNP-heritabilities (0.048-0.12). We observed significant genetic correlations between screen behaviors and psychiatric disorders (rg range: 0.21-0.42). Educational attainment demonstrated negative genetic correlation with screen behaviors, most strongly with social media use (rg = - 0.69). CondFDR analysis identified three novel loci associated with social media use. Thus, we show that screen behaviors are heritable, polygenic traits that partly share genetic signal with mental disorders and educational attainment.

Humans↗
PubMed2026

Polygenic risk score for neurodevelopmental disorders and cognitive impairment at long-term follow-up of first-episode psychosis.

BACKGROUND: One of the most outstanding contributions to the understanding of the etiopathogenesis of schizophrenia spectrum disorders (SSD) was the neurodevelopmental hypothesis. SSD and neurodevelopmental disorders (NDD) share pathogenetic mechanisms and overlapping clinical and cognitive impairment features. METHODS: We investigated whether polygenic risk scores (PRSs) for NDD are associated with cognitive performance in patients with first-episode psychosis (FEP). The sample comprised 127 patients with FEP who were followed up for a mean of 20.9 years. Cognitive examination was performed using the MoCA test at follow-up. Pearson coefficient correlations and multiple regression analyses were performed to examine the contribution of the three PRSs for rare neurodevelopmental conditions (PRSNDD), attention-deficit hyperactivity disorder (PRSADHD) and autism spectrum disorder (PRSASD) to cognitive impairment after allowing for the effect of covariates. Furthermore, we examined the interconnections between the PRS for NDD and cognitive impairment using network analysis (NA), including core premorbid variables. RESULTS: PRSNDD showed significant associations with impairment on visuospatial/executive, attention, and language MoCA subtests, after allowing for the influence of covariates. PRSNDD and PRSADHD, but not PRSASD, were significantly associated with worse performance on the total MoCA score. Moreover, in the network analysis, the relationships between PRSs for NDD and cognitive impairment were highly interconnected with premorbid variables and PRSs for schizophrenia and educational attainment. CONCLUSIONS: These results provide evidence for a possible direct genetic effect on cognitive performance for the PRS of common genetic variations related to neurodevelopment and attention deficit hyperactivity disorder in patients with FEP.

Cognitive impairment↗
PubMed1992

Desipramine facilitation of cocaine abstinence in an adolescent.

An adolescent who was simultaneously dependent on cocaine and treated for attention-deficit hyperactivity disorder (ADHD) with dexedrine developed symptoms of severe depression followed by suicidal behavior. The patient was treated for cocaine craving, depression, and ADHD with desipramine on an inpatient adolescent unit for substance abusers with comorbid psychiatric disorder. The Minnesota Cocaine Craving Scale was used to monitor the cocaine craving. Issues about the strategies for the treatment of cocaine craving and the stimulant treatment/abuse dilemma are discussed with a special emphasis on comorbidity in adolescent substance abusers. Suicidal behavior related to cocaine abuse and craving and the application of the cocaine abstinence three phase model to an inpatient setting are illuminated.

Adolescent↗
PubMed2025

Exploring the shared genetic basis of attention-deficit/hyperactivity disorder and obstructive sleep apnea: A multi-omics analysis.

BACKGROUND: Observational studies have suggested an association between attention-deficit/hyperactivity disorder (ADHD) and obstructive sleep apnea (OSA), but these findings are often inconsistent due to potential biases from medication use, and varying diagnostic criteria. Genetic analyses can help mitigate these confounding factors, providing additional evidence. METHODS: This study evaluated the genetic correlations between ADHD and OSA using Genome-wide association study (GWAS) summary data, applying linkage disequilibrium score regression (LDSC) and SUPER GeNetic cOVariance Analyzer (SUPERGNOVA). Cross-trait association and colocalization analysis identify potential pleiotropic loci. Tissue enrichment analysis and gene-level analysis of shared genes between OSA and ADHD was conducted. Additionally, bidirectional Mendelian randomization was used to assess potential causal relationships. RESULTS: We found significant genetic correlations between ADHD and OSA (rg = 0.309, p = 3.252E-27), and identified 8 novel pleiotropic loci through cross-trait association analysis. Tissue enrichment analysis showed that these shared genes were primarily concentrated in brain tissues, particularly in deep gray matter regions, and were associated with immune and inflammatory pathways. Forward Mendelian Randomization analysis showed that ADHD was significantly associated with the risk of OSA (OR 1.070, 95 % CI 1.013-1.130, p = 0.016), and reverse analysis showed that OSA was significantly associated with the risk of ADHD (OR 1.240, 95 % CI 1.106-1.390, p = 2.213E-4). CONCLUSION: The findings of this study show a significant positive genetic correlation between ADHD and OSA and each is a risk factor for the other. Inflammation in specific brain regions may be the underlying mechanism for their comorbidity.

Humans↗
PubMed2026

Deciphering the Role of LNX2 as a Potential Contributor to Neurodevelopmental Disorders.

BACKGROUND/OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterized by a complex and multifactorial genetic architecture. In this study, we report a male patient, born to non-consanguineous healthy parents, presenting with ADHD and oppositional defiant disorder (ODD). METHODS: Trio-based whole-exome sequencing (WES) was performed in the proband and both parents. Variant classification was performed according to American College of Medical Genetics and Genomics (ACMG) guidelines, and the potential pathogenicity of the identified variant was further assessed through multiple in silico prediction algorithms and protein structural analyses. RESULTS: WES identified a homozygous variant in the LNX2 gene (NM_153371.4: c.1165G>A, p.Ala389Thr), classified as a variant of uncertain significance (VUS) and supported by multiple in silico predictions. LNX2 is expressed during brain development and encodes an E3 ubiquitin ligase involved in neuronal differentiation and synaptic function. The identified variant is located within the PDZ2 domain, a functionally relevant region involved in protein-protein interactions. Although the variant is reported in population databases (gnomAD ID: rs148429804), it has not been associated with any clinical phenotype, and its presence in the homozygous state has been reported only once, remaining extremely rare and lacking clinical annotation. Structural modelling predicted localized rearrangement of the hydrogen-bonding network within the PDZ2 domain without major conformational changes. Integrative transcriptomic, and single-cell analyses further supported the biological relevance of LNX2 in neurodevelopment, highlighting its preferential association with neuronal projection-cell networks, synaptic vesicle trafficking pathways, and neuron-specific regulatory programs. CONCLUSION: Although the identified LNX2 variant cannot be considered causative for the patient's phenotype and a definitive disease-gene relationship cannot be established based on a single individual, the complementary genetic, structural, and transcriptomic findings support the biological plausibility of LNX2 as a candidate gene for neurodevelopmental disorders. Additional independent patients and functional studies will be required to clarify its contribution to human disease.

Child↗
PubMed2026

Comparative Bioavailability of Trimodal (CTx-1301) Versus Bimodal Dexmethylphenidate Modified-Release Formulations in Adults with Attention-Deficit/Hyperactivity Disorder: A Randomized, Single-Dose, Crossover Study.

BACKGROUND AND OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder that often requires sustained symptom control throughout the day. Although bimodal extended-release dexmethylphenidate (d-MPH XR) formulations provide initial and intermediate drug release, they may not consistently maintain therapeutic exposure into the late afternoon and evening. Trimodal formulations with an additional delayed release component may extend drug exposure later in the day, although this remains to be established. To explore differences in pharmacokinetic (PK) profiles between trimodal (CTx-1301) and bimodal delivery of d-MPH XR, a comparative bioavailability study was conducted at the highest and lowest doses for both formulations. METHODS: In this randomized, 4-period, crossover study, adults with ADHD received single doses of CTx-1301 (50 mg and 6.25 mg) and d-MPH XR (40 mg and 5 mg). Comparative bioavailability was assessed through adjusted geometric mean ratios for exposure parameters (maximum observed plasma concentration [Cmax], area under plasma concentration-time curve to last measurable concentration [AUClast] and extrapolated to infinity [AUC0-inf]), with a prespecified bioequivalence range of 0.80 to 1.25. Secondary endpoints included partial AUCs and safety assessments. RESULTS: The study population (N = 45) was predominantly male (88.9%) and White (55.6%), with mean age of 29.6 ± 8.01 years. Adjusted geometric mean ratios comparing the primary exposure parameters (Cmax, AUClast, and AUC0-inf) for CTx-1301 versus d-MPH XR were within the bioequivalence range (0.80-1.25) at both the high and low doses. The CTx-1301-to-d-MPH XR partial AUC ratios were within the bioequivalence range from 0 to 9 hours post-dose. At later intervals (AUC9-12 and AUC12-16), adjusted geometric mean ratios exceeded the upper bioequivalence threshold, consistent with the expected contribution of the third medication release component. Dose proportionality was observed between the two CTx-1301 doses and two d-MPH XR formulations. CTx-1301 was generally well tolerated. The most commonly reported adverse events included tachycardia, insomnia, headache, nausea, and euphoric mood. The incidence of treatment-emergent adverse events was numerically lower with CTx-1301 than with d-MPH XR; however, no statistical analysis was performed. CONCLUSIONS: Key exposure parameters including Cmax, AUClast, and AUC0-inf for trimodal CTx-1301 were statistically bioequivalent to bimodal d-MPH XR. Interval‑specific PK analyses demonstrated higher exposure with CTx‑1301 during later post-dose intervals (9-16 h), consistent with the formulation's third release component. However, the clinical relevance of these PK differences requires further evaluation. CTx-1301 demonstrated dose proportionality and was well tolerated at high and low doses. REGISTRATION: ClinicalTrials.gov, NCT04138498; 19 September 2019.

Humans↗
PubMed2026

Unravelling sex differences in the genetic architecture of anxiety.

BACKGROUND: Anxiety disorders show striking sex differences in prevalence, symptoms, and clinical characteristics, shaping how they manifest and are experienced. METHODS: Here, we report the first sex-specific meta-analysis of genome-wide association studies (GWAS) of anxiety, leveraging two of the largest biobank datasets, UK Biobank and All of Us, comprising 85,042 female cases with 196,789 controls and 36,732 male cases with 136,924 controls. Functional annotation, sex-specific polygenic scores (PGS), and genetic correlations were performed to assess genetic differences and functional implications. RESULTS: In females, 21 lead SNPs were significantly associated with anxiety, compared to five in males. Although the genetic correlation between sexes was high, it was significantly different from one, indicating partially distinct genetic architectures. In addition, both the SNP-based observed and liability-scale heritabilities (assuming a 2:1 female-to-male prevalence ratio) were significantly higher in females. Gene-based tests and functional prioritization identified different genes associated with anxiety in females and males. Moreover, genetic correlation analyses revealed stronger associations of female anxiety with attention-deficit/hyperactivity disorder (ADHD) and body mass index (BMI), whereas male anxiety showed stronger correlations with waist-hip-ratio-adjusted BMI. CONCLUSIONS: While the overall genetic architecture of anxiety is largely shared, our findings reveal distinct sex-specific genetic associations and correlations, highlighting the value of analyzing the sexes separately to uncover genetic signals that may be masked in sex-combined samples.

Female↗
PubMed2024

The role of co-occurring conditions and genetics in the associations of eating disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder.

Eating disorders (EDs) commonly co-occur with other psychiatric and neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD); however, the pattern of family history and genetic overlap among them requires clarification. This study investigated the diagnostic, familial, and genetic associations of EDs with ADHD and ASD. The nationwide population-based cohort study included all individuals born in Denmark, 1981-2008, linked to their siblings and cousins. Cox regression was used to estimate associations between EDs and ADHD or ASD, and mediation analysis was used to assess the effects of intermediate mood or anxiety disorders. Polygenic scores (PGSs) were used to investigate the genetic association between anorexia nervosa (AN) and ADHD or ASD. Significantly increased risk for any ED was observed following an ADHD or ASD diagnosis. Mediation analysis suggested that intermediate mood or anxiety disorders could account for 44%-100% of the association between ADHD or ASD and ED. Individuals with a full sibling or maternal half sibling with ASD had increased risk of AN compared to those with siblings without ASD. A positive association was found between ASD-PGS and AN risk whereas a negative association was found between AN-PGS and ADHD. In this study, positive phenotypic associations between EDs and ADHD or ASD, mediation by mood or anxiety disorder, and genetic associations between ASD-PGS and AN and between AN-PGS and ADHD were observed. These findings could guide future research in the development of new treatments that can mitigate the development of EDs among individuals with ADHD or ASD.

Humans↗
PubMed2025

Psychiatric Polygenic Risk Scores and Week-by-Week Symptomatic Status in Youth with Bipolar Disorder: An Exploratory Study.

Introduction: Prior studies have demonstrated that, in both adults and youth, bipolar disorder (BD) is a polygenic illness. However, no studies have examined polygenic risk scores (PRSs) in relation to the longitudinal course of mood symptoms in youth with BD. Methods: This study included 246 youth of European ancestry with BD (7-20 years old at intake) from the Course and Outcome of Bipolar Youth study and Centre for Youth Bipolar Disorder. Mood symptom severity was assessed at intake and, for 168 participants, prospectively for a median of 8.7 years. PRSs for BD, schizophrenia (SCZ), major depressive disorder (MDD), and attention-deficit/hyperactivity disorder (ADHD) were constructed using genome-wide summary statistics from independent adult cohorts. Results: Higher BD-PRS was significantly associated with lower most severe lifetime depression score at intake (β = -0.14, p = 0.03). Higher SCZ-PRS and MDD-PRS were associated with significantly less time spent in euthymia (SCZ-PRS: β = -0.21, p = 0.02; MDD-PRS: β = -0.22, p = 0.01) and more time with any subsyndromal mood symptoms (i.e., any mania, mixed, or depression symptoms; SCZ-PRS: β = 0.15, p = 0.04; MDD-PRS: β = 0.17, p = 0.01) during follow-up. PRSs for BD and ADHD were not significantly associated with any longitudinal mood variable. Conclusions: This exploratory analysis was the first to examine psychiatric PRSs in relation to the prospective course of mood symptoms among youth with BD. Results from the current study can serve to guide future youth BD studies with larger sample sizes on this topic.

Humans↗
PubMed2026

Genetically predicted childhood traits and parental health and risk of pediatric psychiatric disorders: A 2-sample Mendelian randomization study.

The etiology of pediatric psychiatric disorders is complex, involving intergenerational influences and a child's own developmental health. We aimed to investigate the potential effects of genetically predicted childhood traits (childhood obesity, absence epilepsy, intelligence) and parental health traits (longevity, Alzheimer disease, severe depression) on the risk of several childhood and adolescent psychiatric disorders. We employed a 2-sample Mendelian randomization (MR) design using summary statistics from large-scale genome-wide association studies. Data for parental health exposures were primarily from the UK Biobank. Data for childhood trait exposures were from various consortia. Data for outcomes - conduct disorder, mixed conduct and emotional disorders, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and broader behavioral/emotional and social disorders - were sourced from FinnGen and the Psychiatric Genomics Consortium, among others. We used the inverse-variance weighted method for the primary analysis, with MR-Egger, weighted median, and weighted mode as additional analyses. To test the robustness of the results, we conducted sensitivity analyses using MR-Egger regression, Cochran Q test for heterogeneity, the MR-pleiotropy residual sum and outlier test, and a leave-one-out analysis. Genetic liability for childhood obesity was associated with an increased risk of ASD (odds ratio = 1.06, P = .016) and ADHD (odds ratio = 1.09, P = .026), even though these associations did not withstand multiple testing correction. No other robust, statistically significant causal associations were identified. Sensitivity analyses showed limited evidence of bias from horizontal pleiotropy for the main findings. Our findings provide MR evidence supporting potential links from genetic liability for childhood obesity to increased risks of ASD and ADHD. These results highlight the importance of considering a child's early-life health trajectory in the etiology of pediatric psychiatric disorders.

Humans↗
PubMed2026

Psychiatric and neurological predictors of early ADHD medication discontinuation across the lifespan: a multinational study.

BACKGROUND: Early discontinuation of attention-deficit/hyperactivity disorder (ADHD) medication is common and linked to worse outcomes. Identifying clinical predictors could aid personalised treatment yet evidence is inconsistent across ages and countries/regions. OBJECTIVE: Investigate psychiatric and neurological comorbidity as predictors of early ADHD medication discontinuation in new ADHD medication users across age groups, sex and countries/regions. METHODS: Using health records from eight countries/regions, we identified 1 000 411 (44% female) new ADHD medication users (2011-2020). Discontinuation was defined as a ≥180 day gap between dispensations. We examined 23 indicators of psychiatric or neurological comorbidity, severity and psychotropic medication use. Associations were estimated using Cox regression, pooled with random-effects meta-analyses and stratified by age-at-initiation and sex. FINDINGS: Discontinuation rates varied widely (children 19%-61%, adolescents 37%-68%, young adults 52-67%, adults 38%-68%). In pooled analyses, earlier discontinuation in children was predicted by intellectual disability, autism and use of psychotropic medications (HR range 1.32-1.51), while conduct/oppositional defiant disorder (CD/ODD) was protective (HR 0.83, 95% CI 0.73 to 0.94). In adolescents, no indicators remained statistically significant after multiple-testing control. In young adults, CD/ODD (HR 1.42, 95% CI 1.30 to 1.55), and in adults, schizophrenia (HR 1.25, 95% CI 1.09 to 1.44) and tic disorders (HR 1.27, 95% CI 1.11 to 1.46) predicted earlier discontinuation. Statistical heterogeneity was substantial, largely driven by US estimates. In meta-analyses excluding the USA, additional associations emerged. For example, in children, OCD and anxiety disorders predicted earlier discontinuation, while eating disorders and antidepressants/anxiolytics were protective in adults. Associations with schizophrenia, tic disorders and CD/ODD were no longer significant. Country-specific analyses showed similar association patterns, except in the USA, Hong Kong and the UK. Sex differences were limited. CONCLUSIONS: Children with neuropsychiatric comorbidity and related comedication are more likely to discontinue ADHD medication early, whereas few consistent predictors were seen from adolescence onwards. Marked cross-country variation, particularly in the USA, points to system-level influences on treatment patterns. CLINICAL IMPLICATIONS: Improving ADHD medication persistence will require consideration of healthcare context and age-specific strategies, including close monitoring for children with complex neuropsychiatric profiles, and consideration of broader factors in adolescents and adults, where clinical predictors were limited.

Humans↗
PubMed2026

Atomoxetine Versus Placebo for Cognitive Deficits in Stimulant Use Disorder: A Systematic Review.

BACKGROUND: Stimulant use disorder (StUD), particularly involving cocaine and amphetamines, is associated with significant cognitive impairments that impede recovery and increase relapse risk. Atomoxetine, a selective norepinephrine reuptake inhibitor, has been proposed as a potential treatment given its role in enhancing executive function and its established efficacy in attention-deficit/hyperactivity disorder (ADHD). This systematic review aimed to evaluate the efficacy, cognitive, and mood effects of atomoxetine compared with placebo in individuals with StUD. METHODS: A comprehensive literature search of PubMed, Cochrane CENTRAL, and Embase databases was conducted to identify randomized controlled trials (RCTs) evaluating atomoxetine for StUD. Eligible studies compared atomoxetine with placebo and assessed outcomes related to cognition (attention and response inhibition), stimulant use or abstinence, mood symptoms, and safety. Data were extracted and synthesized qualitatively due to methodological heterogeneity across studies. RESULTS: Nine RCTs met the inclusion criteria. Findings on cognitive outcomes were inconsistent: Some studies reported improvements in attentional bias and inhibitory control, while others showed no significant effects. Atomoxetine did not significantly reduce stimulant use, craving, or sustain abstinence compared with placebo. Limited mood-related benefits were observed, particularly among male participants, although results were variable. Across studies, atomoxetine was well tolerated, with most adverse events mild and transient. CONCLUSION: Despite a compelling neurobiological rationale and evidence of modest cognitive and mood benefits, atomoxetine has not demonstrated consistent efficacy as a monotherapy for StUD. Its favorable safety profile may warrant further investigation in carefully defined populations, such as individuals with comorbid ADHD or in combination with behavioral interventions.

Atomoxetine Hydrochloride↗