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Assessing Undertreatment and Overtreatment/Misuse of ADHD medications in children and adolescents across continents: a systematic review and meta-analysis

Massuti, Rafael; Moreira-Maia, Carlos Renato; Campani, Fausto; Sônego, Márcio; Amaro, Julia; Akutagava-Martins, Gláucia Chiyoko; Tessari, Luca; Polanczyk, Guilherme; Cortese, Samuele; Rohde, Luis Augusto
A controversy exists on whether there is an over or underuse of medications for Attention-Deficit/Hyperactivity Disorder (ADHD). We conducted the first meta-analysis to estimate the rate of ADHD pharmacological treatment in both diagnosed and undiagnosed individuals. Based on a pre-registered protocol (CRD42018085233), we searched a broad set of electronic databases and grey literature. After screening 25,676 abstracts, we retained 36 studies including 104,305 subjects, from which 18 studies met our main analysis criteria. The pooled pharmacological treatment rates were 19.1% and 0.9% in school-age children/adolescents with and without ADHD, respectively. We estimated that for each individual using medication without a formal ADHD diagnosis, there are three patients with a formal diagnosis who might benefit from medication but do not receive it in the US. Our results indicate both overtreatment/misuse of medication in individuals without ADHD and pharmacological undertreatment in youths with the disorder. Our findings reinforce the need for public health policies improving education on ADHD and discussions on the benefits and limitations of ADHD medications.
PMID: 34089763
ISSN: 1873-7528
CID: 4899372

Longitudinal Associations Between Symptoms of ADHD and BMI From Late Childhood to Early Adulthood

Kase, Bezawit E; Rommelse, Nanda; Chen, Qi; Li, Lin; Andersson, Anneli; Du Rietz, Ebba; Vos, Melissa; Cortese, Samuele; Larsson, Henrik; Hartman, Catharina A
BACKGROUND AND OBJECTIVES/OBJECTIVE:Attention-deficit/hyperactivity disorder (ADHD) and obesity are 2 frequent conditions that co-occur, which has implications for the management of both conditions. We hypothesized that ADHD symptoms predict BMI and vice versa from late childhood (10-12 years) up to early adulthood (20-22 years). METHODS:= 2773, 52.5% male, mean age = 11 years at baseline, 5 waves up to mean age 22) from the Tracking Adolescents' Individual Lives Survey cohort. We examined bidirectional relationship between ADHD symptoms (hyperactivity/impulsivity and inattention) and BMI using the random intercept cross-lagged panel model. Time-varying covariates were pubertal status, stimulant use, depressive symptoms, and family functioning, and socioeconomic status was a time-invariant covariate. RESULTS:< .05). No longitudinal direct effects were found between ADHD symptoms and BMI during this period. CONCLUSIONS:Over the course of adolescence, the link between ADHD and BMI is stable and is predominantly with hyperactive and impulsive symptoms rather than inattention. There was no direct effect of ADHD symptoms on BMI increase nor of BMI on enhanced ADHD symptoms during this developmental period. The findings point to a shared genetic or familial background and/or potential causal effects established already earlier in childhood, thus suggesting that intervention and prevention programs targeting overweight and obesity in children with ADHD should be implemented in early childhood.
PMID: 34039717
ISSN: 1098-4275
CID: 4888062

Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review

Correll, Christoph U; Cortese, Samuele; Croatto, Giovanni; Monaco, Francesco; Krinitski, Damir; Arrondo, Gonzalo; Ostinelli, Edoardo G; Zangani, Caroline; Fornaro, Michele; Estradé, Andrés; Fusar-Poli, Paolo; Carvalho, Andre F; Solmi, Marco
Top-tier evidence on the safety/tolerability of 80 medications in children/adolescents with mental disorders has recently been reviewed in this jour-nal. To guide clinical practice, such data must be combined with evidence on efficacy and acceptability. Besides medications, psychosocial inter-ventions and brain stimulation techniques are treatment options for children/adolescents with mental disorders. For this umbrella review, we systematically searched network meta-analyses (NMAs) and meta-analyses (MAs) of randomized controlled trials (RCTs) evaluating 48 medications, 20 psychosocial interventions, and four brain stimulation techniques in children/adolescents with 52 different mental disorders or groups of mental disorders, reporting on 20 different efficacy/acceptability outcomes. Co-primary outcomes were disease-specific symptom reduction and all-cause discontinuation ("acceptability"). We included 14 NMAs and 90 MAs, reporting on 15 mental disorders or groups of mental disorders. Overall, 21 medications outperformed placebo regarding the co-primary outcomes, and three psychosocial interventions did so (while seven outperformed waiting list/no treatment). Based on the meta-analytic evidence, the most convincing efficacy profile emerged for amphetamines, methylphenidate and, to a smaller extent, behavioral therapy in attention-deficit/hyperactivity disorder; aripiprazole, risperidone and several psychosocial interventions in autism; risperidone and behavioral interventions in disruptive behavior disorders; several antipsychotics in schizophrenia spectrum disorders; fluoxetine, the combination of fluoxetine and cognitive behavioral therapy (CBT), and interpersonal therapy in depression; aripiprazole in mania; fluoxetine and group CBT in anxiety disorders; fluoxetine/selective serotonin reuptake inhibitors, CBT, and behavioral therapy with exposure and response prevention in obsessive-compulsive disorder; CBT in post-traumatic stress disorder; imipramine and alarm behavioral intervention in enuresis; behavioral therapy in encopresis; and family therapy in anorexia nervosa. Results from this umbrella review of interventions for mental disorders in children/adolescents provide evidence-based information for clinical decision making.
PMID: 34002501
ISSN: 1723-8617
CID: 4876902

Subgroups of Children with Autism Spectrum Disorder without Intellectual Disability: A Longitudinal Examination of Executive and Socio-Adaptive Behaviors in Adolescence

Rosello, Rocio; Berenguer, Carmen; Martinez-Raga, Jose; Miranda, Ana; Cortese, Samuele
Within the autistic spectrum, there is remarkable variability in the etiology, presentation, and treatment response. This prospective study was designed to identify, through cluster analysis, subgroups of individuals with ASD without intellectual disability (ID) based on the severity of the core symptoms in childhood. The secondary aim was to explore whether these subgroups and a group with typical development (TD) differ in cognitive, adaptive, and social aspects measured in adolescence. The sample at baseline was comprised of 52 children with ASD without ID and 37 children with TD, aged 7-11. Among the ASD group, three clusters were identified. Cluster 1 (40%), 'high severity', presented high symptom severity on the DSM-5 criteria and the Social Communication Questionnaire. Cluster 2 (34%) showed 'moderate severity' on most of the scores. Cluster 3 (25%) corresponded to 'low severity', showing moderate social impairment and low restrictive, repetitive patterns of behavior, interests and activities. At 5-year follow-up, 45 adolescents with ASD without ID and 27 adolescents with TD were assessed. All clusters had significantly more difficulties in EF, ToM, socialization and adaptive behavior compared to TD. Social and adaptive trajectories between the ASD subgroups were relatively different; Cluster 3 showed poorer socialization and daily living skills than the other two subgroups. These findings highlight the importance of fully assessing social, cognitive, and adaptive profiles to develop care plans tailored to specific needs.
PMCID:8160732
PMID: 34065583
ISSN: 2077-0383
CID: 4891332

Editors' Note and Special Communication: Research Priorities in Child and Adolescent Mental Health Emerging From the COVID-19 Pandemic [Editorial]

Novins, Douglas K; Stoddard, Joel; Althoff, Robert R; Charach, Alice; Cortese, Samuele; Cullen, Kathryn Regan; Frazier, Jean A; Glatt, Stephen J; Henderson, Schuyler W; Herringa, Ryan J; Hulvershorn, Leslie; Kieling, Christian; McBride, Anne B; McCauley, Elizabeth; Middeldorp, Christel M; Reiersen, Angela M; Rockhill, Carol M; Sagot, Adam J; Scahill, Lawrence; Simonoff, Emily; Stewart, S Evelyn; Szigethy, Eva; Taylor, Jerome H; White, Tonya; Zima, Bonnie T
PMID: 33741474
ISSN: 1527-5418
CID: 4821912

Developmental outcomes in adolescence of children with autism spectrum disorder without intellectual disability: a systematic review of prospective studies

Rosello, Rocio; Martinez-Raga, Jose; Mira, Alvaro; Girela, Braulio; Cortese, Samuele
Individuals with Autism Spectrum Disorder (ASD) without intellectual disability (ID) represent approximately two-thirds of the ASD population. Here we focused on prospective research assessing different areas of functioning of children with ASD, without ID, until adolescence. Based on a pre-registered protocol (PROSPERO CRD42020189029), a systematic review of prospective studies (published between 01.01.2010 and 01.01.2020) was conducted. Twenty-eight studies met eligibility criteria. Findings indicated that ASD diagnosis and the Intelligence Quotient were highly stable over time across studies. Executive Functioning, Theory of Mind and Central Coherence processes tended to improve, although deficits remained when compared to typically developed controls. Adaptive difficulties and psychiatric comorbidity were relatively stable over time. We discuss potential implications of the findings for clinicians and educators and suggest recommendations for future research.
PMID: 33872683
ISSN: 1873-7528
CID: 4846862

The Association between ADHD and the Severity of COVID-19 Infection

Merzon, Eugene; Weiss, Margaret D; Cortese, Samuele; Rotem, Ann; Schneider, Tzipporah; Craig, Stephanie G; Vinker, Shlomo; Golan Cohen, Avivit; Green, Ilan; Ashkenazi, Shai; Weizman, Abraham; Manor, Iris
OBJECTIVE/UNASSIGNED:Patients with ADHD are at increased risk of acquiring COVID-19. The present study assessed the possibility that ADHD also increases the risk of severe COVID-19 infection. METHOD/UNASSIGNED:We assessed 1,870 COVID-19 positive patients, aged 5 to 60 years, registered in the database of Leumit Health Services (LHS, Israel), February to -June 2020, of whom 231 with ADHD. Logistic regression analysis models evaluated the association between ADHD and the dependent variables of being symptomatic/referral to hospitalization, controlling for demographic and medical variables. RESULTS/UNASSIGNED: = .03). CONCLUSION/UNASSIGNED:ADHD is associated with poorer outcomes in COVID-19 infection.
PMID: 33797281
ISSN: 1557-1246
CID: 4838472

Screening for adult ADHD using brief rating tools: What can we conclude from a positive screen? Some caveats

Chamberlain, Samuel R; Cortese, Samuele; Grant, Jon E
Adult Attention-Deficit/Hyperactivity Disorder (ADHD) is prevalent but often overlooked and undertreated. Left untreated, it is linked to increased risk of untoward outcomes including unemployment, relationship breakups, substance use, driving accidents and other mental health conditions. Several brief screening tools have been developed for adult ADHD. The most frequently used is the World Health Organization's Adult ADHD Self-Report Scale (ASRS V1.1). Here, we show in two independent population samples (UK: N = 642, USA: N = 579) that the tool resulted in considerable overestimation of ADHD, indicating probable ADHD in 26.0% and 17.3% of participants, as compared to expected prevalence of 2.5%. The estimated positive predictive value was only ~11.5%. Both samples had normal levels of trait impulsivity as assessed using the Barratt Impulsiveness Scale. The data indicate that using the ASRS in general population samples will result in 7-10 times over-identification of ADHD. We use these results to highlight how such tools should most appropriately be used. When being used to determine possible cases (such as for onward referral to an ADHD specialist) they should be complemented by clinical assessment - we give examples of how non-specialists might determine this. When measuring ADHD symptoms dimensionally, researchers should be mindful that the ASRS captures impulsive symptoms other than those due to ADHD. Lastly, we note the need to screen for impulse control disorders (e.g., gambling disorder) when using such tools to measure ADHD, be it for onward referral, or for dimensional research studies.
PMCID:7116749
PMID: 33581449
ISSN: 1532-8384
CID: 4786292

Editorial: Why JAACAP Published an "Inconclusive" Trial: Optimize, Optimize, Optimize Psychostimulant Treatment [Editorial]

Cortese, Samuele; Novins, Douglas K
PMID: 32497602
ISSN: 1527-5418
CID: 4469322

A Meta-Analysis Investigating the Association Between Metacognition and Math Performance in Adolescence

Muncer, Gemma; Higham, Philip A.; Gosling, Corentin J.; Cortese, Samuele; Wood-Downie, Henry; Hadwin, Julie A.
Poor math and numeracy skills are associated with a range of adverse outcomes, including reduced employability and poorer physical and mental health. Research has increasingly focused on understanding factors associated with the improvement of math skills in school. This systematic literature review and meta-analysis investigated the association between metacognition and math performance in adolescence (11"“16-year-olds). A systematic search of electronic databases and grey literature (to 04.01.2020) highlighted 31 studies. The quantitative synthesis of 74 effect sizes from 29 of these studies (30 independent populations) indicated a significantly positive correlation between metacognition and math performance in adolescence (r =.37, 95% CI = [.29,.44], p <.001). There was significant heterogeneity between studies. Consideration of online (versus offline) measures of metacognition and more complex (versus simple) measures of math performance, and their combination, was associated with larger effect sizes; however, heterogeneity remained high for all analyses.
SCOPUS:85109316840
ISSN: 1040-726x
CID: 4963432