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ADHD drug treatment and risk of suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality: emulation of target trials

Zhang, Le; Zhu, Nanbo; Sjölander, Arvid; Nourredine, Mikail; Li, Lin; Garcia-Argibay, Miguel; Kuja-Halkola, Ralf; Brikell, Isabell; Lichtenstein, Paul; D'Onofrio, Brian M; Larsson, Henrik; Cortese, Samuele; Chang, Zheng
OBJECTIVE:To examine the effects of drug treatment for attention deficit/hyperactivity disorder (ADHD) on suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality. DESIGN/METHODS:Emulation of target trials. SETTING/METHODS:Linkage of national registers in Sweden, 2007-20. PARTICIPANTS/METHODS:People aged 6-64 years with a new diagnosis of ADHD, who either started or did not start drug treatment for ADHD within three months of diagnosis. MAIN OUTCOME MEASURES/METHODS:First and recurrent events of five outcomes over two years after ADHD diagnosis: suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality. RESULTS:90.1 per 1000 person years; incidence rate ratio 0.98, 0.96 to 1.01). The reduced rates were more pronounced among individuals with previous events, with incidence rate ratios ranging from 0.79 (0.72 to 0.86) for suicidal behaviours to 0.97 (0.93 to 1.00) for accidental injuries. For recurrent events, drug treatment for ADHD was significantly associated with reduced rates of all five outcomes, with incidence rate ratios of 0.85 (0.77 to 0.93) for suicidal behaviours, 0.75 (0.72 to 0.78) for substance misuse, 0.96 (0.92 to 0.99) for accidental injuries, 0.84 (0.76 to 0.91) for transport accidents, and 0.75 (0.71 to 0.79) for criminality. CONCLUSIONS:Drug treatment for ADHD was associated with beneficial effects in reducing the risks of suicidal behaviours, substance misuse, transport accidents, and criminality but not accidental injuries when considering first event rate. The risk reductions were more pronounced for recurrent events, with reduced rates for all five outcomes. This target trial emulation study using national register data provides evidence that is representative of patients in routine clinical settings.
PMCID:12344785
PMID: 40803836
ISSN: 1756-1833
CID: 5907412

Associations of ADHD traits, sleep/circadian factors, depression and quality of life

Nair, Siddhi; Deshpande, Neha; Hill, Catherine; Cortese, Samuele; Van Someren, Eus J W; Chellappa, Sarah Laxhmi
BACKGROUND:Individuals with attention deficit hyperactivity disorder (ADHD) are at a higher risk of depression and lower quality of life (QoL); however, it is unclear whether disrupted sleep and circadian rhythms mediate this increased risk. OBJECTIVES/OBJECTIVE:We investigated whether disruption of self-reported sleep and circadian factors mediate the associations of ADHD traits with depression symptom severity and QoL. METHODS:1364 participants (mean: 51.86 (SD=0.37) years, 75% women) from a large-scale cross-sectional online survey (Netherlands Sleep Registry) completed a sociodemographic questionnaire, the Adult ADHD Rating Scale, Hospital Anxiety and Depression Scale, Satisfaction With Life Scale (SLS) and Cantril Ladder (CL) (QoL measures), Insomnia Severity Index, Pittsburgh Sleep Quality Index and Munich Chronotype Questionnaire. FINDINGS/RESULTS:Higher ADHD traits were significantly associated with depression symptom severity (p=0.03), lower QoL (p<0.001), insomnia severity (p<0.001), lower sleep quality (p<0.001) and later chronotype (p=0.01). No sleep or circadian factor significantly mediated the association of the severity of symptoms of ADHD and depression (all p>0.1). Conversely, only insomnia severity significantly mediated the association of ADHD traits and QoL (SLS: standardised β=-0.10, 95% CI (-0.12 to -0.04); CL: standardised β=0.103, 95% CI (0.04 to 0.16)). CONCLUSION/CONCLUSIONS:ADHD traits were associated with lower QoL and it was partially mediated by insomnia severity. Future studies targeting insomnia complaints in this population may help mitigate their depression complaints and improve their QoL. CLINICAL IMPLICATIONS/CONCLUSIONS:Our results may help current clinical guidelines that do not typically link sleep/circadian complaints to QoL in ADHD assessment.
PMCID:12273136
PMID: 40659535
ISSN: 2755-9734
CID: 5896992

Association of hyperactivity-impulsivity and inattention symptom profiles with suicide attempt: an 18-year population-based cohort study

Spodenkiewicz, Michel; Inja, Ayla; Cortese, Samuele; Galera, Cedric; Ouellet-Morin, Isabelle; Côté, Sylvana M; Boivin, Michel; Vitaro, Frank; Brendgen, Mara; Dionne, Ginette; Renaud, Johanne; Tremblay, Richard E; Turecki, Gustavo; Geoffroy, Marie-Claude; Orri, Massimilano
BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) symptomatology in childhood is associated with a high risk of suicide attempt later in life. However, symptom presentation in ADHD is heterogeneous, and little is known about how suicide risk varies according to different profiles of ADHD symptoms and sex. OBJECTIVE:The aim was to investigate the longitudinal associations between childhood profiles of ADHD symptoms (ie, hyperactivity-impulsivity and inattention) and youth suicide attempt in males and females, separately. METHODS:This population-based cohort study used data from three longitudinal cohorts: the Quebec Longitudinal Study of Child Development (QLSCD), the Quebec Longitudinal Study of Kindergarten Children (QLSKC) and the Quebec Newborn Twin Study (QNTS) for a total of 4399 participants (1490 from the QLSCD, 2134 from the QLSKC and 775 from the QNTS; 50% females) followed up from ages 6-23 years. Symptoms of hyperactivity-impulsivity and inattention were assessed by teachers five times from ages 6-12 years. Suicide attempt in adolescence and young adulthood (by age 23) was self-reported. Multitrajectory modelling was used to identify profiles of ADHD symptoms, and regression analysis was used to test their association with suicide attempt, adjusting for childhood socioeconomic and clinical characteristics. FINDINGS/RESULTS:We identified four ADHD symptom profiles with distinct associations with suicide attempt for males and females. Compared with those with persistently low symptoms, females with persistently high inattention and hyperactivity-impulsivity (OR: 2.54, CI 1.39 to 4.63) or high inattention and low hyperactivity-impulsivity (OR: 1.81, CI 1.21 to 2.70) were at higher risk of suicide attempt, while, among males, only those with decreasing hyperactivity-impulsivity and inattention over time (OR: 2.23, CI 1.20 to 4.13) were at higher risk of suicide attempt. CONCLUSIONS:Risk of suicide attempt in children with ADHD symptoms varies according to both symptom profile and sex, the highest risk being for females with high inattention symptoms (with or without hyperactivity), and males with decreasing symptoms. CLINICAL IMPLICATIONS/CONCLUSIONS:Taking into account differences in both sex and ADHD symptoms profile may be relevant to more accurately identify and manage suicide risk in individuals with high ADHD symptoms, though caution is needed when generalising our population-based findings to clinical populations.
PMID: 40645654
ISSN: 2755-9734
CID: 5891362

General disease factor: evidence of a unifying dimension across mental and physical illness in children and adolescents

Garcia-Argibay, Miguel; Brandt, Valerie; Sun, Hongyi; Solmi, Marco; Lichtenstein, Paul; Larsson, Henrik; Cortese, Samuele
BACKGROUND:) that underlies the vulnerability to both physical and mental conditions could have important implications for our approach to health assessment and treatment. OBJECTIVE:in children and adolescents. METHODS:This Swedish registry-based cross-sectional study included children and adolescents born between 1996 and 2003 with follow-up until 2013. We extracted data on 25 mental and physical health conditions according to the ICD-10 system. To determine the optimal dimensional structure of these conditions, several competing measurement models were tested, including correlated factors, one factor, various bifactor specifications and bifactor exploratory structural equation modelling (ESEM). FINDINGS/RESULTS:=0.423; ECV=0.130) factors also indicated additional significant unique contributions. CONCLUSIONS:underlying both mental and physical conditions, alongside distinct domain-specific factors. These findings have important implications for clinical practice, providing evidence that suggests the need for more integrated approaches to health assessment and treatment that consider the interconnectedness of mental and physical health.
PMCID:12142111
PMID: 40461262
ISSN: 2755-9734
CID: 5862302

Prevalence of mental disorder symptoms among university students: An umbrella review

Paiva, Ursula; Cortese, Samuele; Flor, Martina; Moncada-Parra, Andrés; Lecumberri, Arturo; Eudave, Luis; Magallón, Sara; García-González, Sara; Sobrino-Morras, Ángel; Piqué, Isabella; Mestre-Bach, Gemma; Solmi, Marco; Arrondo, Gonzalo
This umbrella review synthesizes data on the prevalence of mental disorder symptoms among university students worldwide. A systematic search of seven databases (inception-July 23, 2023) followed PRISMA guidelines. We included meta-analyses assessing the prevalence of mental disorder symptoms, evaluating methodological quality with AMSTAR-2. A random-effects meta-analysis was conducted, along with meta-regression and subgroup analyses for moderators (percentage of females, publication date, healthcare-related degrees, COVID-19 pandemic). We included 1,655 primary studies from 62 meta-analyses, encompassing 8,706,185 participants. AMSTAR-2 ratings classified 35 % of meta-analyses as low quality and 65 % as critically low. Pooled prevalence estimates were: depression-mild (35.41 %, CI=33.9-36.93) and severe (13.42 %, CI=8.03-19.92; k=952; n=2,108,813); anxiety-mild (40.21 %, CI=37.39-43.07) and severe (16.79 %, CI=7.21-29.29; k=433; n=1,579,780); sleep disorders (41.09 %, CI=35.7-46.58); eating disorders (17.94 %, CI=15.79-20.20); gambling disorder (6.59 %, CI=5.52-7.75); post-traumatic stress disorder (25.13 %, CI=20.55-30.02); stress (36.34 %, CI=29.36-43.62); and suicide-related outcomes (ideation past 12 months: 10.76 %, CI=9.53-12.06; lifetime ideation: 20.33 %, CI=16.15-24.86; suicide attempt past 12 months: 1.37 %, CI=0.67-2.29; lifetime attempt: 3.44 %, CI=2.48-4.54). Meta-regression analyses identified statistically significant moderators of prevalence such as healthcare academic degrees and the pandemic in the case of depression and studies with more females in the case of sleep disorders. This is the most comprehensive synthesis on the prevalence of mental disorder symptoms in university students, providing crucial insights for clinicians, policymakers, and stakeholders.
PMID: 40480638
ISSN: 1873-7528
CID: 5862912

Definition of Response in Randomized Controlled Trials of Medications for Attention-Deficit/Hyperactivity Disorder Across the Lifespan: A Systematic Review

Roy, Sulagna; Colacicco, Giuseppe; Frigeri, Giorgia; Tarantino, Fabio; Matera, Emilia; Petruzzelli, Maria Giuseppina; Cortese, Samuele
PMID: 40365735
ISSN: 1557-8992
CID: 5844332

Reporting and Representation of Race and Ethnicity in Clinical Trials of Pharmacotherapy for Mental Disorders: A Meta-Analysis

Bellato, Alessio; Raduà, Joaquim; Stocker, Antoine; Lockman, Maude-Sophie; Lall, Anusha; Ravisankar, Vishnie; Obiokafor, Sonia; Machell, Emma; Haq, Sahar; Albiaa, Dalia; Cabras, Anna; Leffa, Douglas Teixeira; Manuel, Catarina; Parlatini, Valeria; Riccioni, Assia; Correll, Christoph U; Fusar-Poli, Paolo; Solmi, Marco; Cortese, Samuele
IMPORTANCE/UNASSIGNED:Representation of race and ethnicity in randomized clinical trials (RCTs) is critical for understanding treatment efficacy across populations with different racial and ethnic backgrounds. OBJECTIVE/UNASSIGNED:To examine race and ethnicity representation and reporting across RCTs of pharmacotherapies for mental disorders. DATA SOURCES/UNASSIGNED:PubMed (Medline), Embase (Ovid), APA PsycInfo, and Web of Science were searched until March 1, 2024, to retrieve network meta-analyses including RCTs of pharmacotherapies for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision mental disorders. STUDY SELECTION/UNASSIGNED:RCTs that recruited people of any age with a diagnosis of a mental disorder and that tested the efficacy of any pharmacologic intervention vs any control arm. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Random-effects logit-transformed proportion meta-analyses were used to estimate prevalence rates of race and ethnicity groups and their temporal trends across RCTs and to compare US RCT prevalence rates with US Census data. The Preferred Reporting Items for Overviews of Reviews was used to report our review. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Reporting of data and percentages of race and ethnicity. The year of publication, type of RCT, geographic location, age group, and sample size were also included. There were no deviations that occurred from the original protocol. RESULTS/UNASSIGNED:Data were obtained from 1683 RCTs (375 120 participants in total). Of these, 1363 (91.7% of participants) included participants aged 18 years or older; 680 RCTs (36.0% of participants) were from the US, 404 (17.1% of participants) were from Europe, and 293 (29.9% of participants) were from multiple geographic locations. Race and ethnicity were reported in 39.2% of RCTs; reporting was the highest in US-based RCTs (58.7%) and lowest in Central and South America (8.7%) and Asia and the Middle East (12.4%). Among participants, 2.7% (95% CI, 2.1%-3.5%) self-reported as Asian, 9.0% (95% CI, 8.1%-10.0%) as Black, 11.0% (95% CI, 9.1%-13.3%) as Hispanic among White, 80.2% (95% CI, 78.8%-81.5%) as White including Hispanic, and 5.8% (95% CI, 5.2%-6.4%) as other race or ethnicity, multiracial, or multiethnic. There was more frequent reporting of race and ethnicity in US RCTs (log odds increased by 0.066 each year) and less frequent reporting in non-US RCTs (log odds increased by 0.023 each year). Studies reporting race and ethnicity did not generally include larger sample sizes (mean sample size, 263.7 [95% CI, 15.0-860.3] participants) compared with those not reporting such data (mean sample size, 196.6 [95% CI, 12.0-601.3] participants), albeit not in all locations. In US RCTs, adults in the other or multiracial and multiethnic category were historically overrepresented, while adults in Asian, Black, Hispanic among White, and White including Hispanic categories were underrepresented; Asian, Black, and Hispanic among White children and adolescents are still currently underrepresented. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The findings of this meta-analysis suggest that differences in reporting race and ethnicity across geographic locations and underrepresentation of certain racial and ethnic groups in US-based RCTs highlight the need for international guidelines to ensure equitable recruitment and reporting in clinical trials.
PMCID:12060014
PMID: 40332916
ISSN: 2168-6238
CID: 5839222

Supporting the next generation of professionals in child and adolescent mental health: the fourth Catania residential course endorsed by ESCAP [Letter]

Riccioni, Assia; Siracusano, Martina; Davico, Chiara; Klauser, Paul; Morcillo, Carmen; Ougrin, Dennis; Vitiello, Benedetto; Plessen, Kerstin J; Danese, Andrea; Speranza, Mario; Bölte, Sven; Cortese, Samuele; Mazzone, Luigi; Armando, Marco
PMID: 40266376
ISSN: 1435-165x
CID: 5830262

Does ADHD treatment inefficacy question its diagnostic validity? - Authors' reply [Letter]

Ostinelli, Edoardo G; Cipriani, Andrea; Cortese, Samuele
PMID: 40245069
ISSN: 2215-0374
CID: 5828702

Understanding Placebo Mechanisms to Reduce Attrition in Psychiatric Trials

Huneke, Nathan T M; Cortese, Samuele; Solmi, Marco
PMID: 40238132
ISSN: 2168-6238
CID: 5828202