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Clinical practices in ADHD management across Europe: findings from the ESCAP research academy survey
Young, Héloïse; Revet, Alexis; Hagstrøm, Julie; Ates, Burçin Özlem; Brænden, Astrid; Grigoriou, Markella; Jarvers, Irina; Jederström, Moa; Jurek, Lucie; Kotsis, Konstantinos; Lestarevic, Sanja; Liebrand, Matthias; Matera, Emilia; Őri, Dorottya; Seker, Asilay; Nikolova, Gordena; Skrypnyk, Tetiana; Solerdelcoll, Mireia; Thoustrup, Christine Lykke; Vertessen, Karen; ,; Klauser, Paul; Cortese, Samuele
In several European countries, national clinical guidelines for the management of ADHD are lacking. In others, guidelines are outdated or do not address more detailed aspects of care, such as medication titration procedures or specific recommendations for school adjustments. Perceptions of the appropriateness of treatment, which influence the delivery of care for ADHD, are shaped by sociocultural aspects. Consequently, practices in the management of ADHD are expected to substantially vary across Europe. To better understand current practices in both pharmacological and non-pharmacological management of ADHD, as well as clinicians' perceptions of treatment appropriateness, we conducted an online survey among European qualified child and adolescent (neuro)psychiatrists and general psychiatrists or trainees involved in the care of children and adolescents with ADHD. The survey was developed and implemented by the European Society for Child and Adolescent Psychiatry (ESCAP) Research Academy, with input from the European ADHD Guidelines Group (EAGG). It was completed by 1,441 clinicians of varying seniority from 23 European countries. The findings provide updated insights into ADHD management across Europe and highlight three key unmet needs. First, several clinically relevant areas lack sufficient evidence, including how to personalise treatment and identify practical predictors of treatment response. Second, some existing evidence has not yet been adequately translated into clinical guidelines or routine practice, particularly regarding comparative treatment effects and dose-response relationships relevant to medication titration. Third, some respondents reported needs that are already addressed in existing international guidelines, suggesting that language barriers may limit access to guidance and underscoring the importance of developing country-specific recommendations in local languages. Overall, this survey - to our knowledge the largest of its kind conducted in Europe - provides valuable information to inform future clinical guidelines, research priorities, and health policy. It also informs future training programmes aimed at reducing bias in the perception and delivery of ADHD treatment.
PMID: 42627426
ISSN: 1435-165x
CID: 6071515
From prediction to decision: prediction-based decision rules and target trial emulation in ADHD
Garcia-Argibay, Miguel; Faraone, Stephen V; Chang, Zheng; Cortese, Samuele; Larsson, Henrik
More than 100 prediction models have been developed to support the diagnosis, prognosis, or treatment of ADHD, yet none has reached routine clinical practice. In this Personal View, we argue that an important reason for this implementation gap is the absence of clearly defined prediction-based decision rules-formalised mappings from a model's output to specific clinical actions. Most published models report discrimination metrics such as the area under the receiver-operating-characteristic curve, but do not specify what a clinician should do differently for a patient classified as at high risk versus low risk. Without this link to action, even an accurate model remains clinically inert. We describe how prediction-based decision rules, combined with target trial emulation of their clinical utility in large observational datasets, offer a feasible path forward. We illustrate the approach with two worked ADHD examples (treatment intensity guided by predicted persistence and medication selection guided by predicted treatment response) and propose four priorities to shift the field from model development towards decision-oriented evaluation and implementation.
PMID: 42624816
ISSN: 2215-0374
CID: 6071506
Evidence based interventions for bipolar disorder across phases and age groups: living umbrella review, evaluation, analysis, and communication hub (U-REACH) project
De Prisco, Michele; Oliva, Vincenzo; Miola, Alessandro; Fornaro, Michele; Dragioti, Elena; Croatto, Giovanni; Carvalho, Andre F; Berk, Michael; Nikolitch, Katerina; Saraf, Gayatri; Yatham, Lakshmi N; Keramatian, Kamyar; Shorr, Risa; Frye, Mark A; Singh, Balwinder; Krinitski, Damir; Højlund, Mikkel; Serretti, Alessandro; Fanelli, Giuseppe; Gomes, Fabiano A; Hansen, Anne Sofie; Nielsen, Rene Ernst; Fusar-Poli, Paolo; Paribello, Pasquale; Manchia, Mirko; Bahji, Anees; Vazquez, Gustavo; Siafis, Spyridon; Leucht, Stefan; Yildiz, Ayşegül; Delorme, Richard; Schaffer, Ayal; Stubbs, Brendon; Rubaiyat, Ruby; Vieta, Eduard; Correll, Christoph U; Moher, David; Cortese, Samuele; Fiedorowicz, Jess G; Radua, Joaquim; Gosling, Corentin J; Solmi, Marco
OBJECTIVES/OBJECTIVE:To systematically evaluate the certainty of evidence for treatment strategies across age groups and mood phases in bipolar disorder, and develop an open access web platform to facilitate shared decision making. DESIGN/METHODS:Living umbrella review, evaluation, analysis, and communication hub (U-REACH) project. DATA SOURCES/METHODS:PubMed, PsycInfo, and Cochrane library databases, from inception to 19 November 2024. ELIGIBILITY CRITERIA FOR SELECTING STUDIES/METHODS:Systematic reviews with network or pairwise meta-analyses of randomised controlled trials of pharmacological, nutraceutical, psychosocial, brain stimulation, or circadian rhythm based treatments, administered as monotherapy (without concurrent interventions), augmentation treatment (interventions added to an ongoing treatment regimen), or combination treatment (simultaneous initiation of two different interventions), examining any age group, bipolar disorder phase (ie, acute bipolar depression, mania or mixed episodes, or maintenance), treatment, control, or outcome. RESULTS:77 studies met the inclusion criteria (21 network meta-analyses and 56 pairwise meta-analyses), including 116 unique pharmacological (n=74), brain stimulation (n=18), nutraceutical (n=13), psychosocial (n=8), and circadian rhythm based (n=3) treatments as monotherapy, augmentation, or combination therapy, along with five control interventions. These studies covered 133 unique outcomes (45 efficacy outcomes and 88 safety outcomes) resulting in 2510 meta-analyses with Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) ratings of the certainty of the evidence as high (n=236), moderate (n=827), low (n=986), and very low (n=461). A communication hub, the Evidence Based Interventions for Bipolar Disorder (EBI-BD) platform, was developed and the full results are freely available (https://ebibd-database.org), including the preference based tool (12 interventions and 17 safety outcomes). Interventions effective across outcomes varied by phases. For bipolar depression, effective interventions in adults were cariprazine, divalproex or valproate, fluoxetine, ketamine (augmentation), lamotrigine, lumateperone, lurasidone, olanzapine, olanzapine with fluoxetine, and quetiapine, whereas effective interventions in children and adolescents were lurasidone and olanzapine with fluoxetine. For mania episodes, effective interventions in adults were aripiprazole, asenapine, carbamazepine, cariprazine, divalproex or valproate, haloperidol, lithium, olanzapine, paliperidone, quetiapine (also augmentation), risperidone (also as augmentation), tamoxifen, and ziprasidone, whereas effective interventions in children and adolescents were aripiprazole, asenapine, olanzapine, quetiapine, and risperidone. For maintenance, interventions effective across outcomes in adults were aripiprazole (also the long acting injectable formulation), asenapine, divalproex or valproate, lithium, olanzapine, group psychoeducation (augmentation), quetiapine, and risperidone long acting injectable formulation. Interventions effective across phases were aripiprazole (also as augmentation and as a long acting injectable formulation), asenapine, cariprazine, cognitive behavioural therapy (augmentation), divalproex or valproate, lamotrigine, lithium, olanzapine (also as augmentation), paliperidone, quetiapine (also as augmentation), and risperidone (also as augmentation and the long acting injectable formulation) (adults). Treatment effects by neuroscience based nomenclature classes are also reported. CONCLUSIONS:The EBI-BD tool can help clinicians make evidence based, personalised treatment decisions for bipolar disorder. This resource can inform clinical guidelines and provides a foundation for continuously improving bipolar disorder care as new evidence emerges. TRIAL REGISTRATION/BACKGROUND:Open Science Framework https://osf.io/pjmvn/ READERS' NOTE: This is a living systematic review and may be updated in the next two years if additional evidence emerges.
PMID: 42580772
ISSN: 1756-1833
CID: 6071237
Real-world ADHD pharmacological treatment patterns and their association with negative clinical outcomes in youth with comorbid autism: a Swedish population-based study
Garcia-Argibay, Miguel; Kuja-Halkola, Ralf; D'Onofrio, Brian M; Lichtenstein, Paul; Chang, Zheng; Larsson, Henrik; Cortese, Samuele
BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) medications can reduce ADHD symptom severity in individuals with comorbid autism spectrum disorder (ASD). However, clinical guidance on pharmacological treatment of ADHD in this clinical population remains limited and inconsistent. Characterising real-world treatment patterns (ie, initiation timing, medication choices, switching, discontinuation) and the impact of alternative medication choices on clinical outcomes is critical for informing evidence-based management strategies. OBJECTIVE:To (1) characterise ADHD pharmacological treatment patterns in youth with ADHD+ASD versus ADHD alone and (2) assess whether using alternative ADHD medications versus methylphenidate is associated with differential changes in negative clinical outcomes among youth with ADHD+ASD. METHODS:This is a population-based cohort study using Swedish national registers. The study included children (<13 years) and adolescents (13-17 years) with an incident ADHD diagnosis between 2007 and 2018 and followed-up until 2021, comparing youth with co-occurring ASD (n=24 117) and ADHD alone (n=79 830). Descriptive outcomes included time to pharmacological treatment initiation, medication type, number of medication switches and discontinuations. The primary outcome was changes in rates of inpatient psychiatric hospitalisations, accidental injuries and specialist care visits for substance use, depressive or anxiety disorders in the 1 year after versus the 1 year before medication initiation. FINDINGS/RESULTS:Individuals with ADHD+ASD experienced longer delays to treatment initiation (12-14% initiated >12 months after diagnosis vs 7-8% in ADHD alone). Children with ADHD+ASD were slightly more likely to discontinue treatment within 3 months (16% vs 12%) and had the highest average number of medication switches within 3 years (2.6; IQR 0.0-2.0). In within-individual analyses, comparisons of alternative ADHD medications versus methylphenidate did not yield statistically significant differences after correcting for multiple comparisons. CONCLUSIONS:Children with ADHD+ASD experienced longer delays to treatment initiation and more frequent medication switching compared with those with ADHD only. The effects of alternative ADHD medication options on key negative clinical outcomes appeared similar to those of methylphenidate. CLINICAL IMPLICATIONS/CONCLUSIONS:These findings suggest that, rather than recommending fixed first-line and second-line treatments for individuals with ADHD-ASD, clinical guidelines should emphasise appropriate training as well as prompt and individualised treatment based on a shared decision-making process.
PMCID:13475623
PMID: 42580811
ISSN: 2755-9734
CID: 6071238
Editorial: Toward Developmental Mechanistic Precision Psychiatry: The Case of Depression Following Attention-Deficit/Hyperactivity Disorder [Editorial]
Cortese, Samuele; Gosling, Corentin J; Garcia-Argibay, Miguel; Bellato, Alessio
PMID: 42595006
ISSN: 1527-5418
CID: 6071294
Candidate Clinico-Demographic Predictors or Moderators of Efficacy and Tolerability of Pharmacological Treatment in Attention-Deficit/Hyperactivity Disorder (ADHD): An Analysis of the MED-ADHD Repository of Randomised Controlled Trials
Roy, Sulagna; Veronesi, Guilherme Fusetto; Mannarini, Sara; Pirolo, Daniele; Bellato, Alessio; Cortese, Samuele; Parlatini, Valeria
BACKGROUND AND OBJECTIVE/OBJECTIVE:Randomised controlled trials (RCTs) have demonstrated that pharmacotherapy reduces symptoms of attention-deficit/hyperactivity disorder (ADHD) at a group level, but efficacy and tolerability vary across individuals. Clinico-demographic characteristics may act as predictors and/or moderators of treatment efficacy and tolerability, but systematic evidence remains limited. Therefore, we systematically analysed RCTs of ADHD medications to identify potential demographic and clinical predictors/moderators of efficacy and tolerability across the lifespan. METHODS:Randomised controlled trials were identified from the MED-ADHD database ( https://med-adhd.org/ ), a repository of RCTs of medications for ADHD in children, adolescents and adults. The database is based on systematic searches of multiple electronic sources, including PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Registry of Controlled Trials and EMBASE, and is also complemented by unpublished data obtained from manufacturers and study authors. We used the most recent (2026) version of MED-ADHD. The risk of bias was assessed using the revised Cochrane risk-of-bias tool (RoB 2). RESULTS:Among the 171 RCTs screened, 62 assessed clinico-demographic factors as possible predictors or moderators of treatment efficacy and tolerability. Age was the most examined characteristic (56.4%) followed by, among the top five, psychiatric comorbidities (53.2%), sex (46.8%), baseline ADHD symptom severity (27.4%), and ADHD presentation (24.2%). Most RCTs reported no significant findings although there was preliminary evidence of associations with age (17.7%), psychiatric comorbidities (17.7%), baseline ADHD symptom severity (16.1%), sex (11.3%), and ADHD presentation (4.8%). Risk of bias was rated high in 37% of RCTs. CONCLUSIONS:Stringent sample selection and reliance on group-level analyses may limit the power to detect predictors and moderators of treatment efficacy and tolerability in classical RCTs. Consequently, the current evidence provides limited and inconsistent guidance on clinically meaningful predictors/moderators. However, variables such as age, psychiatric comorbidities, sex, baseline severity and ADHD presentation have been the most frequently examined with positive findings and may hold promise. Future research should prioritise individual participant data meta-analyses of RCTs, alongside well-powered analyses of a comprehensive observational dataset, to more robustly investigate these associations and support treatment stratification through predictive models.
PMID: 42595937
ISSN: 1179-1934
CID: 6071301
Sex differences in internalising and externalising symptom patterns, pathway and persistence in adolescents receiving psychiatric care: a 2-year follow-up of the MILESTONE European cohort
D'Addazio, Miriam; Leone, Silvia; Leucci, Anna Caterina; Magno, Marta; Atti, Anna Rita; Calza, Stefano; Carnevale, Martina; Caselani, Elisa; Iozzino, Laura; Marcolini, Federica; Martella, Donato; Cortese, Samuele; Dieleman, Gwendolyn; Franić, Tomislav; Maras, Athanasios; McNicholas, Fiona; Purper-Ouakil, Diane; Santosh, Paramala; Schulze, Ulrike M E; Street, Cathy; Singh, Swaran Preet; Tremmery, Sabine; Tuomainen, Helena; van Bodegom, Larissa; Wolke, Dieter; Vicari, Stefano; de Girolamo, Giovanni; ,
BACKGROUND:Sex differences in adolescent mental disorders are well documented, but less is known about how these differences evolve during the transition to adulthood, particularly during the shift from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS), a critical period marked by vulnerability to discontinuity of care. OBJECTIVE:To examine sex-specific differences in psychiatric symptom profiles and clinical trajectories during the CAMHS-AMHS transition using data from the European MILESTONE project, a 2-year longitudinal study. METHODS:A cohort of 1004 adolescents (aged 17-19) in CAMHS was assessed at baseline (T1), 9 months (T2), 15 months (T3) and 24 months (T4). Measures included the Child Behavior Checklist/Adult Behavior Checklist, Health of the Nation Outcome Scales for Children and Adolescents, and the Specific Level of Functioning Scale. Multilevel modelling included sex, diagnosis and time point as covariates, testing three-way interactions for differential trajectories. FINDINGS/RESULTS:Males showed higher symptom severity and impairment across measures, particularly in anxiety/somatic/trauma, eating disorder/obsessive-compulsive disorder (ED/OCD) and schizophrenia. Females exhibited better functioning. Significant sex differences emerged in internalising symptoms (eg, anxiety/somatic/trauma, autism spectrum disorder (ASD)), externalising symptoms (eg, attention deficit hyperactivity disorder (ADHD)), overall psychopathology (eg, ADHD, personality disorder/conduct disorder/substance use disorder) and functioning (eg, ED/OCD, schizophrenia spectrum disorder). CONCLUSIONS:Sex-related differences in symptom severity, diagnosis and functioning persist across the CAMHS-AMHS transition, with males generally more impaired and females showing better adaptive outcomes. CLINICAL IMPLICATIONS/CONCLUSIONS:Identifying sex-specific trajectories can enhance personalised transitional care, reduce misdiagnosis and guide targeted interventions-especially for under-recognised presentations such as ADHD/ASD in females and ED in males. TRIAL REGISTRATION NUMBER/BACKGROUND:ISRCTN83240263.
PMCID:13410704
PMID: 42481172
ISSN: 2755-9734
CID: 6070530
Parent and carer perspectives on behavioural sleep management strategies for children with ADHD
Hornsey, Samantha J; Rowsell, Alison; Hill, Catherine M; Cortese, Samuele; Greenwell, Kate; Muller, Ingrid; ,
OBJECTIVE/BACKGROUND/OBJECTIVE:Attention-Deficit/Hyperactivity Disorder (ADHD) is common in children. Many children with ADHD have chronic insomnia, which is associated with negative outcomes for the child and family and can worsen ADHD symptoms. Behavioural sleep interventions can be effective for children with ADHD and are the recommended first-line approach to management. However, many parents/carers may not have access to, or struggle to implement, interventions in practice. This study explored parents/carers views and experiences of: 1) behavioural sleep management strategies, 2) help-seeking for managing sleep problems and 3) perceptions about a potential digital sleep guide for managing sleep problems. PATIENTS/METHODS/METHODS:A qualitative study using semi-structured interviews of parents/carers of children with ADHD/ADHD traits and chronic insomnia symptoms (CIS). Participants were recruited via social media and purposively sampled for diverse characteristics. Interviews were conducted by telephone/videocall, recorded and transcribed verbatim. Data were analysed using inductive thematic analysis. RESULTS:Eighteen parents/carers took part; two themes and six subthemes were developed. Despite valuing behavioural sleep strategies, parents/carers noted many challenges to engaging with them, including perceiving these strategies to be both ineffective for children with ADHD and not easy to implement in the real world. They described that tiredness, exhaustion, ADHD symptoms and challenging behaviour make parent engagement with strategies difficult. Parents/carers welcomed digital support in principle, particularly because they perceived health professional support to be lacking. However, they noted that digital interventions must address their key support needs regarding flexibility, realistic expectations and a pragmatic approach, as well as comradeship, support and testimonials from other parents/carers. CONCLUSION/CONCLUSIONS:Tailored but flexible support and reassurance are necessary for parents/carers of children with ADHD and CIS. Digital support must validate parent/carer experiences and include experiences from other parents/carers.
PMID: 42470898
ISSN: 1878-5506
CID: 6067502
Global Prevalence of Obsessive-Compulsive and Related Disorders: A Systematic Review and Modeling Study
Jeong, Yi Deun; Son, Yejun; Jeon, Sangeon; Cho, Hanseul; Woo Ryuk, Seung; Jo, Yeona; Fond, Guillaume; Boyer, Laurent; Smith, Lee; Cortese, Samuele; Fusar-Poli, Paolo; Yon, Dong Keon; Solmi, Marco
OBJECTIVE/UNASSIGNED:Obsessive-compulsive disorder (OCD) is one of the common mental disorders globally. However, there are limited studies on the prevalence of OCD and four other disorders categorized under obsessive-compulsive and related disorders, namely, hoarding disorder, excoriation disorder, body dysmorphic disorder, and trichotillomania. The authors sought to fill the epidemiological gap in the literature. METHODS/UNASSIGNED:criteria, were included. A Bayesian hierarchical linear mixed model was used to estimate the lifetime prevalence of OCD at the global, regional, and national levels, with estimates reported with 95% credible intervals. The authors examined the association between OCD prevalence and the Socio-demographic Index (SDI), and estimated age-specific point prevalence of OCD. RESULTS/UNASSIGNED:criteria. Lifetime prevalence of OCD was negatively correlated with SDI, indicating lower prevalence estimates in countries with higher SDI. The age-specific prevalence of OCD increased sharply in the teen years and peaked in the late 20s to early 30s. Point prevalence ranged across studies from 0.98% to 5.81% for hoarding disorder, from 2.33% to 7.68% for excoriation disorder, from 0.44% to 15.21% for body dysmorphic disorder, and from 0.0% to 2.12% for trichotillomania. CONCLUSIONS/UNASSIGNED:This study estimated the global prevalence of OCD according to diagnostic criteria, underscoring the role of diagnostic definitions in shaping epidemiological understanding.
PMID: 42415255
ISSN: 1535-7228
CID: 6063672
ADHD medication discontinuation and non-adherence: a Norwegian population-based register study
Garcia-Argibay, Miguel; Hofstad, Tore; Bjelland, Ingvar; Cortese, Samuele; Mykletun, Arnstein
BACKGROUND:Poor persistence and adherence to attention-deficit/hyperactivity disorder (ADHD) medication is a significant barrier to effective long-term care, particularly during adolescence, yet age-specific and sex-specific trajectories remain poorly characterised. OBJECTIVE:To characterise medication initiation, discontinuation and long-term adherence patterns for children and adolescents diagnosed with ADHD in a real-world setting. METHODS:A nationwide retrospective cohort study, including 8961 children and adolescents (aged <18 years) with a new ADHD diagnosis in child and adolescent mental health services between 1 January 2010 and 31 December 2012, with follow-up until 31 December 2021. Main outcomes were medication initiation rates; time to first medication discontinuation, analysed using Kaplan-Meier estimates and restricted mean survival time at 1 year and longitudinal adherence, measured by the proportion of days covered over 9 years. FINDINGS/RESULTS:Of the 8961 individuals in the cohort (mean age at diagnosis, 12 years; 69% male), 6661 (74.3%) initiated medication, with a median time from diagnosis to initiation of 106 days (IQR 17-231); 55% initiated within 90 days. Discontinuation increased significantly with age; adolescents aged 15-17 years remained on treatment for 31.9 fewer days (95% CI -40.8 to -23.1; p<0.001) in the first year compared with children aged 5-11 years. Females also discontinued significantly earlier than males (difference -13.2 days; 95% CI -19.8 to -6.5; p<0.001). Longitudinal analysis confirmed that older age at initiation and female sex were associated with a significantly steeper decline in medication coverage over time. CONCLUSIONS:Discontinuation and low adherence to ADHD medication were common and increased substantially through adolescence, with females at higher risk of early cessation. CLINICAL IMPLICATIONS/CONCLUSIONS:Late adolescence warrants closer clinical monitoring and shared decision-making to support appropriate treatment continuation or well-informed discontinuation, particularly for older adolescents and females. Integrating structured transition planning and attention to sex-specific barriers may help reduce avoidable non-adherence during this high-risk period.
PMCID:13289004
PMID: 42331561
ISSN: 2755-9734
CID: 6055402