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Neurofeedback for Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis
Westwood, Samuel J; Aggensteiner, Pascal-M; Kaiser, Anna; Nagy, Peter; Donno, Federica; Merkl, Dóra; Balia, Carla; Goujon, Allison; Bousquet, Elisa; Capodiferro, Agata Maria; Derks, Laura; Purper-Ouakil, Diane; Carucci, Sara; Holtmann, Martin; Brandeis, Daniel; Cortese, Samuele; Sonuga-Barke, Edmund J S; ,
IMPORTANCE/UNASSIGNED:Neurofeedback has been proposed for the treatment of attention-deficit/hyperactivity disorder (ADHD) but the efficacy of this intervention remains unclear. OBJECTIVE/UNASSIGNED:To conduct a meta-analysis of randomized clinical trials (RCTs) using probably blinded (ie, rated by individuals probably or certainly unaware of treatment allocation) or neuropsychological outcomes to test the efficacy of neurofeedback as a treatment for ADHD in terms of core symptom reduction and improved neuropsychological outcomes. DATA SOURCES/UNASSIGNED:PubMed (MEDLINE), Ovid (PsycInfo, MEDLINE, Embase + Embase Classic), and Web of Science, as well as the reference lists of eligible records and relevant systematic reviews, were searched until July 25, 2023, with no language limits. STUDY SELECTION/UNASSIGNED:Parallel-arm RCTs investigating neurofeedback in participants of any age with a clinical ADHD or hyperkinetic syndrome diagnosis were included. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Standardized mean differences (SMDs) with Hedges g correction were pooled in random effects meta-analyses for all eligible outcomes. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was ADHD total symptom severity assessed at the first postintervention time point, focusing on reports by individuals judged probably or certainly unaware of treatment allocation (probably blinded). Secondary outcomes were inattention and/or hyperactivity-impulsivity symptoms and neuropsychological outcomes postintervention and at a longer-term follow-up (ie, after the last follow-up time point). RCTs were assessed with the Cochrane risk of bias tool version 2.0. RESULTS/UNASSIGNED:A total of 38 RCTs (2472 participants aged 5 to 40 years) were included. Probably blinded reports of ADHD total symptoms showed no significant improvement with neurofeedback (k = 20; n = 1214; SMD, 0.04; 95% CI, -0.10 to 0.18). A small significant improvement was seen when analyses were restricted to RCTs using established standard protocols (k = 9; n = 681; SMD, 0.21; 95% CI, 0.02 to 0.40). Results remained similar with adults excluded or when analyses were restricted to RCTs where cortical learning or self-regulation was established. Of the 5 neuropsychological outcomes analyzed, a significant but small improvement was observed only for processing speed (k = 15; n = 909; SMD, 0.35; 95% CI, 0.01 to 0.69). Heterogeneity was generally low to moderate. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Overall, neurofeedback did not appear to meaningfully benefit individuals with ADHD, clinically or neuropsychologically, at the group level. Future studies seeking to identify individuals with ADHD who may benefit from neurofeedback could focus on using standard neurofeedback protocols, measuring processing speed, and leveraging advances in precision medicine, including neuroimaging technology.
PMID: 39661381
ISSN: 2168-6238
CID: 5762682
Commentary: Using QbTest for monitoring pharmacological treatment response in ADHD - are we there yet?
Bellato, Alessio; Parlatini, Valeria; Groom, Madeleine J; Hall, Charlotte L; Hollis, Chris; Simonoff, Emily; Thapar, Anita; Cortese, Samuele
Individuals with attention-deficit/hyperactivity disorder (ADHD) exhibit varied responses to pharmacological treatments (e.g. stimulants and non-stimulants). Accurately and promptly detecting treatment-related improvements, response failure, or deterioration poses significant challenges, as current monitoring primarily relies on subjective ratings. In this commentary, we critically evaluate the evidence supporting the use of QbTest for objectively monitoring ADHD treatment response in clinical practice. We also offer recommendations for future research, advocating for rigorous clinical trials and longitudinal studies to further explore the potential utilisation of QbTest and other tools for monitoring treatment responses in individuals with ADHD.
PMID: 39513414
ISSN: 1469-7610
CID: 5752172
Longitudinal Associations Between Physical Health Conditions in Childhood and Attention-Deficit/Hyperactivity Disorder Symptoms at Age 17 Years
Reed, Claire; Cortese, Samuele; Golm, Dennis; Brandt, Valerie
OBJECTIVE:Attention-deficit/hyperactivity disorder (ADHD) is associated with lower birth weight, but also with obesity in childhood. Findings on the direction of this association are mixed. This study investigated the relationship between weight and ADHD from birth across development. METHOD/METHODS:We used data from the Millennium Cohort Study (MCS), collected at 7 time points between age 9 months and 17 years. ADHD diagnosis status and scores on the Strength and Difficulties Questionnaire (SDQ) were used to create an ADHD group and a control group. Random intercept cross-lagged panel models were conducted in female individuals (n = 4,051) and male individuals (n = 3,857) to examine bidirectional associations between body mass index (BMI) z scores and SDQ scores between ages 3 and 17 years. Analyses were adjusted for common risk factors for ADHD and obesity, such as sex assigned at birth, multiple births, and ADHD medication status. RESULTS:Children in the ADHD group were significantly lighter in weight at birth than the control group (t[5674] = 2.65, 95% CI = 0.02, 0.14, p = .008) and were significantly more likely to have obesity at age 5 years onward (odds ratio range = 1.57-2.46, relative risk range 0.98-2.29). Path analyses conducted separately for male and female individuals showed that higher ADHD symptoms in female individuals at ages 7, 11, and 14 years significantly predicted higher BMI z scores at ages 11, 14, and 17 years, respectively. In male individuals, this association was seen only between ages 11 and 14 years (β = 0.07; 95% CI = 0.04-0.10, p < .001). CONCLUSION/CONCLUSIONS:Results suggest that interventions for children with ADHD, and their parents, should begin as soon as possible, ideally prenatally. Developmental sex differences should be considered.
PMID: 39510314
ISSN: 1527-5418
CID: 5752082
Reply: the inclusion of methylphenidate in the WHO list of essential medicines is endorsed by millions of people with ADHD [Letter]
Cortese, Samuele; Coghill, David; Fegert, Joerg M; Mattingly, Gregory W; Rohde, Luis A; Wong, Ian C K; Faraone, Stephen V
PMID: 39196420
ISSN: 1435-165x
CID: 5729772
Safety of psychotropic medications in pregnancy: an umbrella review
Fabiano, Nicholas; Wong, Stanley; Gupta, Arnav; Tran, Jason; Bhambra, Nishaant; Min, Kevin K; Dragioti, Elena; Barbui, Corrado; Fiedorowicz, Jess G; Gosling, Corentin J; Cortese, Samuele; Gandhi, Jasmine; Saraf, Gayatri; Shorr, Risa; Vigod, Simone N; Frey, Benicio N; Delorme, Richard; Solmi, Marco
Weighing risks and benefits of the use of psychotropic medications during pregnancy remains a challenge worldwide. We systematically assessed the strength of associations between psychotropic medication use in pregnant people with mental disorders and various adverse health outcomes in both pregnant people and foetuses. Systematic reviews with meta-analyses of observational studies investigating the association between exposure to psychotropic medication in pregnancy and any adverse health outcomes were included. Credibility was graded into convincing, highly suggestive, suggestive, weak or not significant. Quality of the meta-analyses and of individual studies were assessed with A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) the Newcastle-Ottawa Scale (NOS), respectively. We considered 21 meta-analyses encompassing 17,290,755 participants (AMSTAR 2 high = 1, low = 12, or critically low = 8). Evidence was suggestive for: (1) preterm birth in pregnant people with either any mental disorder (equivalent odds ratio 1.62 (95% confidence interval 1.24-2.12) or depression (1.65 [1.34-2.02]) receiving antidepressants during any trimester of pregnancy; (2) small for gestational age for pregnant people with depression receiving a SSRI during any trimester of pregnancy (1.50 [1.19-1.90]); and (3) major congenital malformation (1.24 [1.09-1.40]) or cardiac malformations (1.28 [1.11-1.47]) in babies for pregnant people with depression or anxiety receiving paroxetine during first trimester of pregnancy. Additional associations were supported by weak evidence, or were not statistically significant. This umbrella review found no convincing or highly suggestive level of evidence of adverse health outcomes associated with psychotropic medication use in pregnant people with mental disorders.
PMID: 39266712
ISSN: 1476-5578
CID: 5690682
Systematic Review: Assessment of Blinding Integrity in 161 Randomized Controlled Trials of Attention-Deficit/Hyperactivity Disorder Medications [Letter]
Fusetto Veronesi, Guilherme; Huneke, Nathan T M; Shah, Mohammad; Cortese, Samuele
We carried out the first systematic review to gauge if assessment of blinding was conducted in RCTs investigating medications for ADHD. Put of 161 RCTs form the dataset MED-ADHD (https://med-adhd.org/), we found only one RCT that reported blinding integrity, indicating that assessments of blinding integrity are very rarely conducted in the field. While our findings are not meant to invalidate the evidence on the benefits of ADHD medications, they suggest an opportunity to improve reporting of clinical trials in ADHD.
PMID: 39243852
ISSN: 1527-5418
CID: 5689862
First evidence on a general disease ("d") factor underlying psychopathology and physical illness in adolescents
Stevanovic, Dejan; Cirovic, Nikola; Cortese, Samuele; Knez, Rajna; Kerekes, Nóra
The coexistence of mental and physical health illnesses could be accounted for by an underlying general disease factor (termed d-factor), reflecting theoretical underpinnings based on possible genetic and pathophysiological overlapping mechanisms. This study evaluated whether the d-factor underlies mental and physical health illnesses in adolescents. A series of confirmatory factor analyses were conducted using data from 1120 adolescents. The proposed common underlying factor, we believe is the d-factor, was consistently present across different modeling approaches, including unidimensional, correlated-factor, and bifactor models. The best model fit was achieved with the bifactor model represented by mental, neurological, and psychical conditions tested. The first compelling evidence was provided supporting the existence of the transdiagnostic d-factor in youth, opening the door to innovative research of comorbid mental and physical health conditions.
PMID: 38849671
ISSN: 1435-165x
CID: 5665912
The ADHD Assessment Quality Assurance Standard for Children and Teenagers (CAAQAS)
Young, Susan; Absoud, Michael; Al-Attar, Zainab; Ani, Cornelius; Colley, William; Cortese, Samuele; Crame, Jo; Gudjonsson, Gisli; Hill, Peter; Hollingdale, Jack; Mukherjee, Raja A S; Ozer, Susan; Partridge, Gavin; Smith, Jade; Woodhouse, Emma Louise; Lewis, Alexandra
Around 5% of the children and teenagers worldwide are affected by Attention-Deficit/Hyperactivity Disorder [ADHD], making it a major public health concern. Recently, demand for assessments has substantially increased, putting strain on healthcare and waiting lists. There is concern that pressure to clear service bottlenecks is leading to variable quality and reliability of ADHD assessments in this population. The ADHD Assessment Quality Assurance Standard for Children and Teenagers [CAAQAS] aims to address this by proposing a quality framework for ADHD assessments in this population. CAAQAS is intended to complement formal training, provide support to clinicians, inform commissioners, and empower children, teenagers, and caregivers on what to expect from an assessment and assessment report. Our goal is to promote evidence-based high-quality assessments, improve diagnostic accuracy, and reduce the risks of overdiagnosis, misdiagnosis, and underdiagnosis. Seven key topics were identified by authors which guided the development of this expert consensus statement. It was agreed that a high-quality diagnostic assessment of ADHD in this population commences with advance preparation to facilitate engagement of the child or teenager and caregivers. The consensus agreed that the minimum/essential standards for assessing and diagnosing ADHD adopt a systematic approach from pre-assessment through assessment to post-diagnostic stage, enabling ADHD to be disentangled from differential diagnoses. The process applies multi-source information to inform an assessment of development history and early risk factors, history of physical, mental health and other neurodevelopmental conditions, family, educational, and social histories. Assessment of core ADHD symptoms should include specific developmentally appropriate examples of associated difficulties and impairments. Neuropsychiatric and physical comorbidities should be assessed and identified. Recommendations for report writing are intended to facilitate effective communication between ADHD specialists and other services, and we highlight the importance of linking the diagnosis to an appropriate post-diagnostic discussion. Further, we discuss core competencies required to conduct a diagnostic assessment of ADHD in children and teenagers.
PMCID:11682937
PMID: 39737064
ISSN: 1176-6328
CID: 5805472
A systematic review and meta-analysis comparing the severity of core symptoms of attention-deficit hyperactivity disorder in females and males
Young, Susan; Uysal, Omer; Kahle, Jennifer; Gudjonsson, Gisli H; Hollingdale, Jack; Cortese, Samuele; Sakalli-Kani, Ayse; Greer, Ben; Cocallis, Kelly; Sylver, Nicole; Yilmaz, Ugur Eser; Semerci, Bengi; Kilic, Ozge
In the past decade, there have been substantial changes in diagnostic nomenclature. This study investigated sex differences in attention-deficit/hyperactivity disorder (ADHD) symptom severity based on Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, DSM-IV(TR), and DSM-5 criteria, separating rating scale and clinical interview data in children and adults with ADHD. PubMed, PsycINFO, and Scopus were searched for published studies (1996-2021) reporting severity of attention, and hyperactivity/impulsivity in males and females. We compared data: (1) across the entire lifespan aggregating rating scale and clinical interview data (51 studies), (2) drawing solely on rating scale data (18 studies), and (3) drawing solely on clinical interview data (33 studies). Fifty-two studies met inclusion criteria comparing data for females (n = 8423) and males (n = 9985) with ADHD across childhood and/or adulthood. In total, 15 meta-analyses were conducted. Pooled data across the lifespan aggregating both rating scale and clinical diagnostic interview data, showed males had significantly more severe hyperactivity/impulsivity symptoms than females. Rating scale data were similar; boys had significantly more severe hyperactivity/impulsivity than girls. In adulthood, men were rated to have significantly more severe inattention than women with no difference in the hyperactivity/impulsivity dimension. All significant differences were of small effect size. No significant sex differences in the severity of symptoms emerged for clinical interview data for children or adults, in contrast. Possible reasons for the discrepancy in findings between rating scales and clinical diagnostic interviews are discussed.
PMCID:11578919
PMID: 39494848
ISSN: 1469-8978
CID: 5803502
Publisher Correction: Prospective analysis of sex differences and factors associated with suicidal thoughts and behaviours in young people from the MILESTONE Italian sample
Torino, Gabriele; Leone, Silvia; Cortese, Samuele; Dieleman, Gwen; Gerritsen, Suzanne; Maffezzoni, Deborah; Martella, Donato; Micciolo, Rocco; Singh, Swaran; Street, Cathy; Tuffrey, Amanda; Walker, Leanne; Zamparini, Manuel; de Girolamo, Giovanni; ,
PMID: 39604396
ISSN: 2045-2322
CID: 5780002