Factors associated with pharmacological treatment in children with Attention-Deficit/Hyperactivity Disorders: retrospective study of a series of 77 cases in a single third-level reference center in Apulia Region

Factors associated with pharmacological treatment in children with Attention-Deficit/Hyperactivity Disorders: retrospective study of a series of 77 cases in a single third-level reference center in Apulia Region | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Factors associated with pharmacological treatment in children with Attention-Deficit/Hyperactivity Disorders: retrospective study of a series of 77 cases in a single third-level reference center in Apulia Region Simone Amendola, Isabella Fanizza, Sara Scoditti, Marta De Rinaldis, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1841430/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Nov, 2023 Read the published version in Italian Journal of Pediatrics → Version 1 posted You are reading this latest preprint version Abstract Background: The present study analyzed data of children and adolescents with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) who referred to the ADHD reference center Scientific Institute IRCCS E. Medea (Brindisi, Italy) for ADHD pharmacotherapy initiation and monitoring overtime. The main aim of the study was to examine differences between patients according to pharmacological treatment status, i.e., treatment continuation vs discontinuation. Methods: Seventy-seven children and adolescents (mean age at pharmacotherapy initiation= 9.5, standard deviation= 2.6) with ADHD received drugs treatment for ADHD at the reference center between January, 2013 and May, 2022. Demographic and clinical data were obtained from the Italian Registry for ADHD and medical records. Child Behavior Checklist (CBCL) available data were used. Results: Pharmacological treatment status was examined for patients (n= 63) with at least 12 months of follow-up after the first pharmacological administration for ADHD. After starting pharmacotherapy treatment, 49 (77.8%) patients were still on treatment whereas 14 (22.2%) discontinued it. No between group difference was observed on demographic and clinical data except for quotient of intelligence/intellectual disability and rule-breaking behavior (n= 40). Conclusions: The findings of this study highlighted the need of periodical assessment monitoring difficulties with (or reasons for poor) treatment compliance in order to provide individualized care, and were discussed according to recent scientific evidence. psychopharmacology medication drug prescribing adherence treatment persistence interruption Background Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by age-inappropriate levels of attention and/or impulsivity that last for at least six months (1). In order to diagnose ADHD, symptoms must occur in different contexts (e.g., family and school), cause impairment of daily functioning, first appear in childhood, and not being better explained by another disorder (2). Willcutt et al. (3) synthesized findings of 86 studies for a total of 163,688 children and adolescents showing ADHD prevalence of 5.9% among the former and 7.1% among the latter. The condition is generally associated with poor academic outcomes, peer problems, and family stress and difficulties (4–9). ADHD clinical presentation can be differentiated in a predominantly inattentive subtype, a predominantly hyperactive/impulsive subtype, and a combined subtype (1). Further, the disorder frequently co-occurs with internalizing and externalizing disorders. For example, compared with girls without ADHD, girls with ADHD were significantly more likely to show comorbid internalizing (anxiety, depression) and externalizing (oppositional defiant disorder, conduct disorder) psychopathology (10). Near seven out of ten young patients with ADHD met the diagnostic criteria for at least one comorbid psychiatric disorder, with learning, sleep and oppositional disorders the most frequent (11). Previous studies also analysed psychopathological subtypes in children and adolescents with ADHD demonstrating the existence of different groups, i.e., low symptoms, mainly externalizing, mainly internalizing, and high symptoms of psychopathology (12,13). Studies on ADHD and its treatment in Italy Reale and Bonati (14) combined findings of fifteen previous studies on prevalence of ADHD in Italian young people. Overall, the prevalence of ADHD was 2.9% (range: 1.1-16.7%) whereas counting only subjects with an ADHD diagnosis confirmed by clinical assessment reduced prevalence to 1.4% (range: 1.1-3.1%) (14). The guidelines of the Italian Society of Childhood and Adolescent Neuropsychiatry (15) recommend the use of a multimodal approach as the most suitable for the treatment of ADHD. It consists of non-pharmacological treatments that directly involve the patient, his family and the school (e.g., cognitive-behavioral therapies, parent and teacher training). Drug therapy should be considered in the most severe cases of ADHD, in the absence of responses to psycho-behavioral treatments (15,16). The Italian National Registry for ADHD became operational in 2007 to monitor ADHD drugs use in childhood and adolescence and verify therapy safety, benefits and compliance (17–19). Changes in pharmacological treatment of ADHD in Italy overtime has been previously discussed (20) and relevant publications analyzed data from the registry (21–23). Maschietto and colleagues (21) showed that ADHD prevalence was mainly stable (1.2% in 2007 and 1.1% in 2010) whereas incidence of new cases decreased (0.06% in 2008 and 0.03% in 2010) between 2007 and 2010. One third of patients diagnosed with ADHD did not received any type of treatment (watchful waiting approach) whereas some form of treatment was prescribed to the rest (around 73% yearly). Prevalence of multimodal treatment increased overtime from 7% (in 2007) to 16.7% (in 2010) whereas psycho-behavioral interventions decreased from 65% to 58.2%. Among the latter, parent training was prescribed in 66.1% of cases whereas cognitive-behavioral therapy in 24.8%. Finally, children aged 6-10 years represented almost 60% of total ADHD cases. Similar findings were observed with samples of patients evaluated by 18 ADHD regional reference centres in Lombardia (Italy) (23,24). Patients with drug prescriptions more commonly presented symptoms of clinical severity (as evaluated by clinicians using the item of the Clinical Global Impression), combined type of ADHD, clinical dis-attention and hyperactivity (as reported by parents) compared to subjects treated with psychological interventions alone (23). In a recent update (25), the presence of comorbidity (i.e., oppositional defiant disorder, intellectual disability, tic and coordination disorder) was more likely in patients treated with pharmacotherapy than psychological treatment. These results are in line with those of a recent prospective population-based Norwegian study (26). Treatment (dis-)continuation and psychopathology The available treatments are only partially effective in reducing symptoms of ADHD, especially non-drug treatments (2). Reale et al. (11) analyzed clinical improvement (as evaluated by clinicians using a single item of the Clinical Global Impression) after one year of treatment showing no significant difference between treatment groups (also including a no treatment category) in patients with only ADHD (i.e., no comorbidity). Whereas a significant difference was observed between treatment groups in patients with ADHD and comorbidity showing that combined treatment (methylphenidate plus psychological intervention) and no treatment categories were contributing the most to the chi-square value (in opposite direction). Thus, identifying factors associated with treatment (dis-)continuation may have important clinical implications in terms of tailoring the intervention to the individual child (27). Adherence to and persistence of ADHD pharmacological treatment are generally low among young people with ADHD and vary between 40-70% and 30-50%, respectively (28–30). Low adherence and persistence are associated with several factors, including older age, being male, late diagnosis of ADHD, family history for ADHD, high level of paternal education, parental separation, absence of comorbidities, multiple daily doses, high doses, side effects, lack of efficacy, stigma, higher ADHD symptoms (2,27,31–39). Few studies examined the relationship between psychopathological symptoms and (dis-)continuation of drug treatment for ADHD showing mixed findings. Atzori and colleagues (27) retrospectively compared 134 patients referring to the Centre for Pharmacological Therapies in Children and Adolescents Psychiatry (Cagliari, Italy) between 1998 and 2005, and taking methylphenidate with at least three years of follow-up. The presence of comorbidity (besides the significant effects of younger age, being female and not living with both parents) predicted continuation of therapy at three years. On the other hand, the absence of comorbidity (besides the significant effect of older age) was associated with therapy discontinuation due to functional remission. Finally, discontinuing therapy for other reasons (e.g., poor compliance, reduction of efficacy) was not associated with comorbidity whereas it was associated with older age when starting therapy and hyperactive subtype of ADHD (27). The relationship between psychiatric comorbidity and persistence of ADHD therapy has been confirmed by a retrospective study using Korean Health Insurance data from 2007 to 2011 (40). Other studies who did not differentiate between reasons for discontinuing ADHD therapy (i.e., remission vs other reasons) showed no association between therapy continuation and psychopathology. For example, Palli et al. (36) did not find evidence of an association between continuation of ADHD therapy and comorbid psychopathology using Medicaid Analytic eXtract data from Texas, New York, California and Illinois (United States) between 2003 to 2005. Whereas continuation of ADHD therapy was associated with prescriptions of other psychotropic drug classes (other than stimulants). These findings could be explained considering that multivariate models were fitted including both comorbid psychopathologies and drugs usually used to treat them. Thus, it is possible that the significant effect of other psychotropic drug classes masked or mediated the effect of the association between comorbid psychopathology and continuation of ADHD therapy. Further, the association observed may be due to clinical severity of cases taking multiple medications despite the effects of other important factors (i.e., number of comorbidities, recent mental health-related hospitalization) were controlled in the analyses. Another explanation for the study findings points to the possible effect of the propensity to assume medications that would lead to an association between the continuation of ADHD pharmacotherapy and prescriptions of other psychotropic drugs. In accordance with the latter explanation, Safavi et al. (41) showed that comorbidity was not associated with adherence to ADHD pharmacotherapy in 118 children with ADHD who referred to a child psychiatry clinic in Iran in 2018. Whereas ADHD children with a family history of psychotropic medication use reported higher adherence to ADHD pharmacotherapy compared to those with no family history (41). Similarly, another study (42) conducted with fifty children referring to a tertiary care center in Mumbai (India) did not find evidence of associations between adherence to ADHD pharmacotherapy and conduct disorder, oppositional defiant disorder and emotional problems. Whereas adherence correlated negatively with the severity of ADHD. A recent study (43) analyzing adherence to methylphenidate in Japan using retrospective data demonstrated no association between adherence and concomitant use of antipsychotic, antidepressants and anxiolytics. Finally, Cheung et al. (44) reported no significant univariate association between methylphenidate treatment adherence at two years and the five Diagnostic and Statistical Manual of Mental Disorders - oriented scales of the Child Behavior Checklist (CBCL), and symptoms of ADHD, in a sample of 264 children in the Netherlands. Study aims and hypotheses The first aim of this study was to present demographic and clinical characteristics of children and adolescent aged 5 to 17 years who received drugs treatment for ADHD at the reference center Scientific Institute IRCCS “E. Medea” (Brindisi, Italy) between January, 2013 and May, 2022. The second aim of the study was to increase scientific knowledge on the association between (dis-)continuation of ADHD pharmacotherapy, demographic and clinical characteristics, in particular symptoms of psychopathology when initiating ADHD pharmacotherapy. Considering previous mixed findings on the relationship between treatment (dis-)continuation and psychopathology, the study was exploratory in nature and we expected higher psychopathology in patients who continued pharmacotherapy compared to those who did not it (27,40) or no between group difference (36,41–44). Methods Participants and procedure This retrospective study included children and adolescents between 6 and 17 years old referring to one (Scientific Institute IRCCS “E. Medea” in Brindisi, Italy) of the Puglia reference prescription centers for ADHD pharmacological treatment between January, 2013 and May, 2022. Prescription centers confirm the ADHD diagnosis and establish the pharmacological therapy monitoring it overtime. According to the resolution no. 1242 by the Puglia Regional Council, 26 July 2007 (DGR. 1242/2007), five reference prescription centers were accredited as centers specialized in diagnosis and treatment of ADHD (45). In December 13, 2016, regional prescription centers were increased to eight (DGR. 2036/2016). Patients were included in this study if they were enrolled in the Italian National Registry for ADHD and received a prescription for methylphenidate (MPH) from the reference center Scientific Institute IRCCS “E. Medea” in Brindisi (Italy). Written informed consent for medication administration and analysis of clinical data for scientific research was obtained from both parents and patients. The first drug administration, the “testing dose” (5 mg of immediate-release methylphenidate) takes place at the Scientific Institute during hospitalization in order to monitor potential side effects and vital signs (e.g., brain and cardiac activity). In absence of relevant side effects, patients started chronic treatment with modified-release methylphenidate and a first follow-up at one-month. Drug dose for modified-release methylphenidate ranges from 0.3 to 0.5 mg/kg until a total maximum of 60 mg/die administered in a unique dose. For some patients, 5 mg of immediate-release methylphenidate is also administered in the afternoon in order to help patients in completing homework assignments. Drug dose is based on improvement in child behavior and psychosocial functioning. An annual “drug holiday” period (approximately of two/three months) during summer vacation takes place for the majority of patients and according to their symptomatology. It is planned in order to decrease the effects of medication on height and weight as well as to assess the need for continuing medication during the first month(s) of the new school academic year. The research was approved by the local ethical committee of the “Research Ethics Committee – IRCCS Istituto Tumori Giovanni Paolo II - Bari (Italy).” Instruments The following demographic and clinical data was obtained from the Registry for ADHD and medical records: age at treatment initiation, sex, city of residence, months between diagnosis and pharmacotherapy, months of pharmacotherapy, quotient of intelligence (QI), ADHD diagnosis subtype, comorbidity and pharmacological treatment status. Pharmacological treatment status was defined as “in treatment” and “treatment discontinuation” as at May, 2022, for participants for which at least 12 months of follow-up after the first pharmacological administration for ADHD were available. The Child Behavior Checklist (CBCL/6–18) (46,47) was used to explore emotional and behavioural symptoms, competencies and adaptive functioning as reported by parents. Items are scored on a three-point scale (0 = not true, 1 = somewhat or sometimes true, and 2 = very or often true) and refer to symptoms presentation during the preceding six months. Internalizing and externalizing broad band symptoms dimensions were empirically developed from the CBCL (Achenbach & Rescorla, 2000). All CBCL scales have a T-score mean of 50 and standard deviation of 10 and different norms are provided for each gender across different age ranges. Previous research showed the usefulness of syndrome scales for a complete and accurate assessment of young patients (48–50). The most recent CBCL completed before the first methylphenidate administration was analysed. Statistical analysis Descriptive statistics (number, frequency, mean and standard deviation) were computed to explore the characteristics of the sample and of subgroups according to pharmacological treatment status. Subgroup analysis based on pharmacological treatment status included participants (n= 63) for which at least 12 months of follow-up after the first pharmacological administration for ADHD were available at May 2022. Between group differences according to pharmacological treatment status were analyzed using the Chi-square test and student-t statistics for group comparison on categorical and continuous variables, using Cramer’s V and Cohen’s d as estimate of effect size, respectively. When the assumption on equality of variance (tested using Levene’s test) was violated (p< 0.05 or approaching significance at p< 0.10) Welch homogeneity correction was applied. Interpretation of effect size for Cramer’s V were moderate if between .2 and .6, and strong if higher than 0.6, whereas, for Cohen’s d, moderate if between .5 and .8, and strong if higher than .8. Subsequently, two multivariable logistic regression models were used to test associations between pharmacological treatment status and variables of interest ( model 1 ) and psychopathology as measured by the CBCL subscales ( model 2 ), including variables whose bivariate associations were significant (p< 0.05) or approaching significance (p< 0.10) based on subgroup analysis. Model 2 included only participants (n= 40) for which the CBCL was available. Indeed, CBCL data was not available for all children and adolescents. Specifically, some of them have been previously evaluated for ADHD receiving the diagnosis by medical doctors specialized in child and adolescent neuropsychiatry to subsequently refer to the Scientific Institute IRCCS “E. Medea” for the first prescription of the ADHD pharmacological therapy and its monitoring overtime. Usually, for those patients, a new diagnostic assessment is not implemented. As a preliminary analysis, differences between participants, whose data was considered for the subgroup comparisons, with (n= 40) and without (n= 23) CBCL evaluation were explored showing no difference in demographic and clinical characteristics. All analysis were performed using JASP version 0.16.0.0 (51) and p value < 0.05 was considered to be significant. Results ADHD was diagnosed at a mean of 8.8 years of age (Table 1). Eight months generally occurred between diagnosis and pharmacotherapy initiation. 26% of patients lived in the same city as Scientific Institute location (i.e., Brindisi) whereas the rest lived in other Apulia provinces (i.e., 37.7% in Lecce, 20.8% in Taranto, 11.7% in Bari, 3.9% in other provinces). The majority (92%) of patients were diagnosed with combined type of ADHD, 6.5% with the inattentive type and only one (1.3%) with the hyperactive one. 77% of patients showed one or more comorbid disorder as follows: 54.6% one, 19.5% two, 1.3% three and 1.3% four disorders in comorbidity, respectively. The most frequent comorbid conditions were disruption and impulse control disorders, intellectual and learning disability. Near all patients (97.4%) received at least one form of treatment other than pharmacotherapy. Specifically, 52% of patients received one other treatment, 44.2% two and 1.3% three other treatments. The most frequent treatments provided were cognitive-behavioral therapy and parent training. [insert table 1 about here] Bivariate associations 63 of 77 patients had at least 12 months of follow-up after the first pharmacological administration for ADHD as at May 2022. Of these, 14 (22.2%) patients discontinued ADHD pharmacotherapy. As expected these two groups differed on total months in pharmacotherapy for ADHD (Table 1). On the contrary, no significant difference was observed for age at diagnosis and age at the first assumption of pharmacotherapy for ADHD, diagnosis, comorbidity and other treatments. Further, patients in treatment showed a higher QI mean score than patients who discontinued treatment (borderline significant p value of 0.091). Considering between groups comparisons on the CBCL, differences on the externalizing and rule breaking behavior subscales were borderline significant (p= 0.075 and p= 0.053, respectively) with higher symptoms in patients who discontinued compared to those that continued ADHD pharmacotherapy (Table 2). Further, patients who discontinued ADHD pharmacotherapy showed a significantly (p= 0.047) higher mean T total score compared to patients who continued treatment. [insert table 2 about here] Logistic regression of associations with ADHD pharmacotherapy status Considering demographic and clinical characteristics, no significant bivariate association was observed between pharmacological status and variables of interest with the exception of a trend for significant association with QI. Thus, model 1 was no longer analyzed. In order to test model 2, bivariate associations were computed considering only participants with CBCL data (n= 40). Patients in treatment were significantly (χ² (1)= 3.971, p= 0.046, Cramer’s V= .32) less likely to show intellectual disability (14.7%, n= 5) compared to those who discontinued treatment (50%, n= 3) whereas no other difference was shown for demographic and clinical data. Thus, model 2 included intellectual disability and rule-breaking behavior CBCL subscale. The results of the model are shown in Table 3 and demonstrated significant associations between pharmacotherapy status and rule-breaking behavior (p= 0.032), and intellectual disability (p= 0.028). [insert table 3 about here] Discussion Findings of the present study demonstrated that one in five (n= 14, 22% of patients with at least one year follow-up) young patients discontinued ADHD pharmacotherapy after a mean of 12 months of pharmacotherapy (SD= 14.2), whereas the rest (n= 49, 78%) has continued using medication for a mean period of 51 months (SD= 25.3). This finding is consistent with the scientific literature on the topic (27,28,30). A previous study (22) conducted with a large Italian sample of children and adolescents with ADHD showed that 21.5% of patients interrupted treatment after two/four months of pharmacotherapy due to decision of parents/health professional, adverse events, lost to follow-up, ineffectiveness and other reasons. Considering group differences according to pharmacological treatment status, a trend for group difference for QI was present for which patients in treatment showed a higher QI mean score than patients who discontinued treatment. On the other hand, no significant difference was observed for age at diagnosis, age at the first assumption of pharmacotherapy for ADHD and other demographic characteristics, diagnosis, comorbidity and other treatments. Further, considering the subsample (N= 40) with data at the CBCL, intellectual disability and rule-breaking behavior were associated with pharmacological treatment status. Patients with high rule-breaking behavior and intellectual disability were more likely to discontinuing ADHD drug treatment. These findings were unexpected since previous studies mainly showed no difference between groups (36,41–44) or that comorbid disorders predicted treatment continuation (27,40). However, Nayak et al. (42) have recently found evidence that adherence negatively correlates with the severity of ADHD. Between studies differences may be accounted by differences in sample and methodology. Masi et al. (52) have recently highlighted that intellectual disability increases the risk of any adverse event, especially irritability, suggesting that it may be linked to low tolerability to drug treatment. On the other hand, Nayak et al. (42) showed that when controlling for the presence of side effects, the association between ADHD severity and poor adherence became non-significant. It follows that intellectual disability and rule-breaking behavior may interact with side effects with these patients experiencing relevant increase in irritability with drug treatment (53), or they could experience side effects as more distressing, both leading to treatment discontinuation. An alternative explanation concerns the fact that these patients may be less compliant to treatment and/or that their family may experience relevant difficulty in their management leading to treatment interruption. Furthermore, according to our clinical experience, patients with intellectual disability and their families may have high or unrealistic expectations on ADHD pharmacotherapy in improving overall cognitive functioning. Therefore, they may be at higher risk of discontinuing treatment, at least in our sample. Finally, patients with high symptoms of rule-breaking behavior could experience pharmacotherapy as negatively affecting their personality or that medications take away their personality changing the way they perceive themselves. Thus, treatment discontinuation may also be related to the relationship between medication, behavior and identity. However, the association between treatment status and disruption and impulse control disorders was not significant. Taken all together, our findings add knowledge on the association between psychopathology and treatment (dis-)continuation proposing potential explanations. Studies with large samples are needed to support our findings and clarify the relationship between psychopathology and treatment (dis-)continuation using both dimensional and categorical approaches, and controlling for important covariates. Limitations of the study The study was conducted with a population of participants from a delimited geographic and cultural area, that is, one ADHD reference center located in a region of South Italy. As a consequence, the results may not be generalized to other different populations or settings. The retrospective design of the study and the small sample size may also limit their generalizability. Further, the data analysed were collected as part of the ADHD clinical routine management rather than for specific research purposes. Finally, information on patients’ reasons for treatment discontinuation were missing because patients were lost to follow-up, limiting results interpretation. The lack of data on reasons for discontinuation, parental/family and social characteristics may limit the interpretability of our findings since adherence in young people could be determined or at least influenced by these factors (28,42,44). As a consequence, our findings should be interpreted considering the above limitations. Despite these limitations, the present study included data from patients encountered in a clinical setting incorporating real-life variability in symptoms of psychopathology at presentation (without the application of exclusion criteria) supporting its ecological validity. Conclusions The findings of the present study showed that patients who discontinued treatment showed higher frequency of intellectual disability and higher rule-breaking behaviour, before the first pharmacological administration for ADHD, compared to patients who continued treatment. Our findings highlight the need of periodical assessment monitoring difficulties with (or reasons for poor) treatment compliance as well as side effects in order to provide individualized care. Abbreviations ADHD: Attention-Deficit/Hyperactivity Disorder CBCL: Child Behavior Checklist. QI: quotient of intelligence. Declarations Ethics approval and consent to participate All methods were carried out in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The research was approved by the local ethical committee of the “Research Ethics Committee – IRCCS Istituto Tumori Giovanni Paolo II - Bari (Italy).” Written informed consent for medication administration and analysis of clinical data for scientific research was obtained from both parents and patients. Consent for publication Written informed consent for medication administration and analysis of clinical data for scientific research was obtained from both parents and patients. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare to have no competing interest. Funding No funding was received for this specific study. Authors' contributions Conceptualization, S.A. and A.T.; methodology and formal analysis, S.A.; sample recruitment, I.F. and M.D.R.; investigation, I.F. and A.T.; data curation, I.F., S.S. and S.A.; writing - original draft preparation, S.A. and A.T.; supervision, A.T. All authors have read and agreed to the published version of the manuscript. Acknowledgements This work was supported by the Italian Ministry of health RC 2018-2020. References American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA; 2013. Faraone SV, Banaschewski T, Coghill D, Zheng Y, Biederman J, Bellgrove MA, et al. The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder. Neurosci Biobehav Rev. 2021;128:789–818. Willcutt EG. The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics. 2012;9(3):490–9. Arnold LE, Hodgkins P, Kahle J, Madhoo M, Kewley G. 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The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials. PLoS One. 2017;12(7):e0180355. Frank E, Ozon C, Nair V, Othee K. Examining why patients with attention-deficit/hyperactivity disorder lack adherence to medication over the long term: a review and analysis. J Clin Psychiatry. 2015;76(11):e1459-1468. Gajria K, Lu M, Sikirica V, Greven P, Zhong Y, Qin P, et al. Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder - a systematic literature review. Neuropsychiatr Dis Treat. 2014;10:1543–69. Gau SSF, Chen SJ, Chou WJ, Cheng H, Tang CS, Chang HL, et al. National survey of adherence, efficacy, and side effects of methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan. J Clin Psychiatry. 2008;69(1):131–40. Khan MU, Aslani P. A Review of Factors Influencing the Three Phases of Medication Adherence in People with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2019;29(6):398–418. Palli SR, Kamble PS, Chen H, Aparasu RR. Persistence of stimulants in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2012;22(2):139–48. Storebø OJ, Pedersen N, Ramstad E, Kielsholm ML, Nielsen SS, Krogh HB, et al. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies. Cochrane Database Syst Rev. 2018;5:CD012069. Wang LJ, Yang KC, Lee SY, Yang CJ, Huang TS, Lee TL, et al. Initiation and Persistence of Pharmacotherapy for Youths with Attention Deficit Hyperactivity Disorder in Taiwan. PLoS One. 2016;11(8):e0161061. Wong ICK, Asherson P, Bilbow A, Clifford S, Coghill D, DeSoysa R, et al. Cessation of attention deficit hyperactivity disorder drugs in the young (CADDY)--a pharmacoepidemiological and qualitative study. Health Technol Assess. 2009;13(50):iii–iv, ix–xi, 1–120. Bhang SY, Kwack YS, Joung YS, Lee SI, Kim B, Sohn SH, et al. Factors that Affect the Adherence to ADHD Medications during a Treatment Continuation Period in Children and Adolescents: A Nationwide Retrospective Cohort Study Using Korean Health Insurance Data from 2007 to 2011. Psychiatry Investig. 2017;14(2):158–65. Safavi P, Saberzadeh M, Tehrani AM. Factors Associated with Treatment Adherence in Children with Attention Deficit Hyperactivity Disorder. Indian J Psychol Med. 2019;41(3):252–7. Nayak AS, Nachane HB, Keshari P, Parkar SR, Saurabh KH, Arora M. Prescription patterns and medication adherence in preadolescent children with attention deficit hyperactivity disorder. Indian Journal of Psychiatry. 2021;63(3):274–8. Ishizuya A, Enomoto M, Tachimori H, Takahashi H, Sugihara G, Kitamura S, et al. Risk factors for low adherence to methylphenidate treatment in pediatric patients with attention-deficit/hyperactivity disorder. Sci Rep. 2021;11(1):1707. Cheung K, Dierckx B, El Marroun H, Hillegers MHJ, Stricker BH, Visser LE. Methylphenidate Treatment Adherence and Persistence in Children in the Netherlands. J Child Adolesc Psychopharmacol. 2021;31(3):205–13. Germinario EAP, Arcieri R, Marzi M, Panei P, Vella S. Registro nazionale ADHD (Attention-Deficit/Hyperactivity Disorder): dati dal 2007 al 2016. (Rapporti ISTISAN 16/37). Roma: Istituto Superiore di Sanità; 2016. Achenbach T, Rescorla L. Manual for the ASEBA (Achenbach System of Empirically Based Assessment) Preschool Forms & Profiles. Burlington: University of Vermont, Research Center for Children, Youth, & Families; 2000. Frigerio A, Cattaneo C, Cataldo M, Schiatti A, Molteni M, Battaglia M. Behavioral and Emotional Problems Among Italian Children and Adolescents Aged 4 to 18 Years as Reported by Parents and Teachers. European Journal of Psychological Assessment. 2004;20(2):124–33. Bellina M, Brambilla P, Garzitto M, Negri GAL, Molteni M, Nobile M. The ability of CBCL DSM-oriented scales to predict DSM-IV diagnoses in a referred sample of children and adolescents. Eur Child Adolesc Psychiatry. 2013;22(4):235–46. Ivanova MY, Achenbach TM, Dumenci L, Rescorla LA, Almqvist F, Weintraub S, et al. Testing the 8-Syndrome Structure of the Child Behavior Checklist in 30 Societies. Journal of Clinical Child & Adolescent Psychology. 2007;36(3):405–17. Nobile M, Colombo P, Bellina M, Molteni M, Simone D, Nardocci F, et al. Psychopathology and adversities from early- to late-adolescence: a general population follow-up study with the CBCL DSM-Oriented Scales. Epidemiology and Psychiatric Sciences. 2013;22(1):63–73. JASP Team. JASP (Version 0.16.3)[Computer software]. 2022. Masi G, Pfanner C, Liboni F, Lenzi F, Villafranca A, D’Acunto G, et al. Acute Tolerability of Methylphenidate in Treatment-Naïve Children with ADHD: An Analysis of Naturalistically Collected Data from Clinical Practice. Pediatr Drugs. 2022;24(2):147–54. Wigal T, Greenhill L, Chuang S, McGOUGH J, Vitiello B, Skrobala A, et al. Safety and Tolerability of Methylphenidate in Preschool Children With ADHD. Journal of the American Academy of Child & Adolescent Psychiatry. 2006;45(11):1294–303. Tables Table 1 . Demographic and clinical characteristics of total sample and pharmacological treatment status subgroups. Total sample (N= 77) M (SD) In treatment (n= 49) M (SD) Treatment discontinuation (n= 14) M (SD) t / χ² (df) Cohen’s d / Cramer’s V Age, 9.5 (2.6) 9.3 (2.6) 10.2 (2.8) -1.213 (61) .37 Males, n (%) 66 (85.7) 43 (87.8) 12 (85.7) 0.041 (1) .03 Age at diagnosis 8.8 (2.6) 8.6 (2.4) 9.2 (2.9) -0.775 (61) .24 Months between diagnosis and pharmacotherapy b 8.4 (11.8) 7.4 (11.2) 11.9 (15.2) -1.046 (17.4) .34 Months of pharmacotherapy b 36.3 (28.5) 50.8 (25.3) 12.2 (14.2) 7.361 (38.61) * 1.88 ASL of residence in the same city as Scientific Institute location, n (%) 20 (26) 13 (26.5) 3 (21.4) 0.150 (1) .05 Diagnosis, n (%) 1.552 (1) .16 ADHD-C 71 (92.2) 44 (89.8) 14 (100) ADHD-H 1 (1.3) - - ADHD-I 5 (6.5) 5 (10.2) 0 Comorbidity, n (%) One or more 59 (76.6) 37 (75.5) 10 (71.4) 0.096 (1) .04 Autism 4 (5.2) 3 (6.1) 1 (7.1) 0.019 (1) .02 Intellectual disability 16 (20.8) 8 (16.3) 4 (28.6) 1.059 (1) .13 Learning disability 16 (20.8) 11 (22.5) 4 (28.6) 0.225 (1) .06 Language disorder 7 (9.1) 7 (14.3) 0 2.25 (1) .19 Emotional disorder 6 (7.8) 5 (10.2) 0 1.552 (1) .16 Disruption and impulse control disorders 16 (20.8) 7 (14.3) 3 (21.4) 0.416 (1) .08 Epilepsy 1 (1.3) 0 1 (7.1) - - Migraine 1 (1.3) 1 (2.1) 0 - - Developmental coordination disorders 4 (5.2) 2 (4.1) 2 (14.3) 1.907 (1) .17 Congenital abnormalities non specified and chromosomal abnormalities 5 (6.5) 3 (6.1) 1 (7.1) 0.019 (1) .02 Abnormal EEG 3 (3.9) 3 (6.1) 0 0.9 (1) .12 QI a 81.1 (19.9) 83.4 (20) 70.6 (20.6) 1.728 (45) .64 Other treatment, n (%) One or more 75 (97.4) 48 (98) 13 (92.9) 0.922 (1) .12 Counselling 1 (1.3) Parent training 37 (48.1) 22 (44.9) 4 (28.6) 1.198 (1) .14 Cognitive-behavioral therapy 69 (89.6) 45 (91.8) 12 (85.7) 0.474 (1) .09 Child training 0 - - Psychodynamic psychotherapy 0 - - Family therapy 0 - - Other 4 (5.2) 4 (8.2) 0 1.22 (1) .14 Note . The sum of patients of “in treatment” and “treatment discontinuation” groups does not equal that of patients of total sample since not all patients was included in subgroup analysis. a : data available for 58 patients totally and for 47 in group comparison. b : Welch homogeneity correction was applied. M: mean, SD: standard deviation, ASL: local Health Service office, ADHD-C: attention deficit/hyperactivity disorder combined type, ADHD-H: attention-deficit/hyperactivity disorder hyperactive type, ADHD-I : attention-deficit=hyperactivity disorder inattentive type, QI : quotient of intelligence. * p< 0.05. Table 2 . CBCL subscales’ mean T scores of total sample and pharmacological treatment status subgroups. Total sample a (n= 50) M (SD) In treatment (n= 34) M (SD) Treatment discontinuation (n= 6) M (SD) t (df) Cohen’s d Activities 29.7 (9.9) 29.9 (11.6) 29.2 (6.9) 0.146 (38) .07 Social 35.3 (11.5) 36.4 (13.2) 35.2 (7.7) 0.229 (38) .10 School 34.6 (7.9) 34.4 (8.4) 37.9 (6.1) -0.949 (38) .42 Total competence 27.9 (13) 28.3 (15) 28.7 (8.3) -0.054 (38) .02 Anxious/depressed 63.5 (8.3) 63.2 (8.4) 61.3 (7.7) 0.518 (38) .23 Withdrawn/depressed b 62.2 (10.1) 63.5 (11) 61.3 (7) 0.640 (9.91) .24 Somatic complaints 59.3 (8.6) 59 (9.1) 59 (10.8) -0.007 (38) .003 Social problems 65.6 (8.3) 66.7 (8.2) 61 (9.6) 1.544 (38) .68 Thought problems 67.9 (12.6) 67.2 (13.5) 73.3 (9.3) -1.055 (38) .47 Attention problems 71.3 (8.3) 71.7 (9.1) 70.2 (3.7) 0.392 (38) .17 Rule-breaking behavior 65.7 (9.3) 63.9 (9.1) 71.7 (7.1) -2.002 (38) .89 Aggressive behavior b 71.1 (11.1) 71 (11.8) 72.7 (6.2) -0.507 (12.61) .17 Internalizing 63.2 (9) 63 (10.2) 65 (6.1) -0.462 (38) .20 Externalizing b 68.5 (8.6) 67.8 (9.2) 71.3 (2.7) -1.849 (28.87) .52 Total score b 69.1 (7) 68.4 (7.8) 71.7 (2) -2.069 (32.87) * .57 Note . a : total sample of patients for which data for the CBCL was available, b : Welch homogeneity correction was applied. * p< 0.05. Table 3 . Logistic regression model of factors associated with pharmacotherapy discontinuation (vs. continuation). Standardized estimate OR (95% CI) Wald statistic (df) Intellectual disability 1.267 22.83 (1.40, 373.24) * 4.81 (1) Rule-breaking behavior 1.600 1.19 (1.02, 1.40) * 4.58 (1) Note . N= 40. * p< 0.05. Cite Share Download PDF Status: Published Journal Publication published 14 Nov, 2023 Read the published version in Italian Journal of Pediatrics → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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In order to diagnose ADHD, symptoms must occur in different contexts (e.g., family and school), cause impairment of daily functioning, first appear in childhood, and not being better explained by another disorder\u0026nbsp;(2). Willcutt et al.\u0026nbsp;(3)\u0026nbsp;synthesized findings of 86 studies for a total of 163,688 children and adolescents showing ADHD prevalence of 5.9% among the former and 7.1% among the latter. The condition is generally associated with poor academic outcomes, peer problems, and family stress and difficulties\u0026nbsp;(4\u0026ndash;9). ADHD clinical presentation can be differentiated in a predominantly inattentive subtype, a predominantly hyperactive/impulsive subtype, and a combined subtype\u0026nbsp;(1). Further, the disorder frequently co-occurs with\u0026nbsp;internalizing and externalizing disorders. For example, compared with girls without ADHD, girls with ADHD were significantly more likely to show comorbid internalizing (anxiety, depression) and externalizing (oppositional defiant disorder, conduct disorder) psychopathology\u0026nbsp;(10). Near seven out of ten young patients with ADHD met the diagnostic criteria for at least one comorbid psychiatric disorder, with learning, sleep and oppositional disorders the most frequent\u0026nbsp;(11). Previous studies also analysed psychopathological subtypes in children and adolescents with ADHD demonstrating the existence of different groups, i.e., low symptoms, mainly externalizing, mainly internalizing, and high symptoms of psychopathology\u0026nbsp;(12,13).\u003c/p\u003e\n\u003ch2\u003eStudies on ADHD and its treatment in Italy\u003c/h2\u003e\n\u003cp\u003eReale and Bonati\u0026nbsp;(14)\u0026nbsp;combined findings of fifteen previous studies on prevalence of ADHD in Italian young people. Overall, the prevalence of ADHD was 2.9% (range: 1.1-16.7%) whereas counting only subjects with an ADHD diagnosis confirmed by clinical assessment reduced prevalence to 1.4% (range: 1.1-3.1%)\u0026nbsp;(14).\u003c/p\u003e\n\u003cp\u003eThe guidelines of the Italian Society of Childhood and Adolescent Neuropsychiatry\u0026nbsp;(15)\u0026nbsp;recommend the use of a multimodal approach as the most suitable for the treatment of ADHD. It consists of non-pharmacological treatments that directly involve the patient, his family and the school (e.g., cognitive-behavioral therapies, parent and teacher training). Drug therapy should be considered in the most severe cases of ADHD, in the absence of responses to psycho-behavioral treatments\u0026nbsp;(15,16).\u003c/p\u003e\n\u003cp\u003eThe Italian National Registry for ADHD became operational in 2007 to monitor ADHD drugs use in childhood and adolescence and verify therapy safety, benefits and compliance\u0026nbsp;(17\u0026ndash;19). Changes in pharmacological treatment of ADHD in Italy overtime has been previously discussed\u0026nbsp;(20)\u0026nbsp;and relevant publications\u0026nbsp;analyzed data from the registry\u0026nbsp;(21\u0026ndash;23). Maschietto and colleagues\u0026nbsp;(21)\u0026nbsp;showed that ADHD prevalence was mainly stable (1.2% in 2007 and 1.1% in 2010) whereas incidence of new cases decreased (0.06% in 2008 and 0.03% in 2010) between 2007 and 2010. One third of patients diagnosed with ADHD did not received any type of treatment (watchful waiting approach) whereas some form of treatment was prescribed to the rest (around 73% yearly). Prevalence of multimodal treatment increased overtime from 7% (in 2007) to 16.7% (in 2010) whereas psycho-behavioral interventions decreased from 65% to 58.2%. Among the latter, parent training was prescribed in 66.1% of cases whereas cognitive-behavioral therapy in 24.8%. Finally, children aged 6-10 years represented almost 60% of total ADHD cases. Similar findings were observed with samples of patients evaluated by 18 ADHD regional reference centres in Lombardia (Italy)\u0026nbsp;(23,24).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients with drug prescriptions more commonly presented symptoms of clinical severity (as evaluated by clinicians using the item of the Clinical Global Impression), combined type of ADHD, clinical dis-attention and hyperactivity (as reported by parents) compared to subjects treated with psychological interventions alone\u0026nbsp;(23). In a recent update\u0026nbsp;(25), the presence of comorbidity (i.e., oppositional defiant disorder, intellectual disability, tic and coordination disorder) was more likely in patients treated with pharmacotherapy than psychological treatment. These results are in line with those of a recent prospective population-based Norwegian study\u0026nbsp;(26).\u003c/p\u003e\n\u003ch2\u003eTreatment (dis-)continuation and psychopathology\u003c/h2\u003e\n\u003cp\u003eThe available treatments are only partially effective in reducing symptoms of ADHD, especially non-drug treatments\u0026nbsp;(2).\u0026nbsp;Reale et al.\u0026nbsp;(11)\u0026nbsp;analyzed clinical improvement (as evaluated by clinicians using a single item of the Clinical Global Impression) after one year of treatment showing no significant difference between treatment groups (also including a no treatment category) in patients with only ADHD (i.e., no comorbidity). Whereas a significant difference was observed between treatment groups in patients with ADHD and comorbidity showing that combined treatment (methylphenidate plus psychological intervention) and no treatment categories were contributing the most to the chi-square value (in opposite direction). Thus,\u0026nbsp;identifying factors associated with treatment (dis-)continuation may have important clinical implications in terms of tailoring the intervention to the individual child\u0026nbsp;(27).\u003c/p\u003e\n\u003cp\u003eAdherence to and persistence of ADHD pharmacological treatment are generally low among young people with ADHD and vary between 40-70% and 30-50%, respectively\u0026nbsp;(28\u0026ndash;30). Low adherence and persistence are associated with several factors, including older age, being male, late diagnosis of ADHD, family history for ADHD, high level of paternal education, parental separation, absence of comorbidities, multiple daily doses, high doses, side effects, lack of efficacy, stigma, higher ADHD symptoms\u0026nbsp;(2,27,31\u0026ndash;39).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFew studies\u0026nbsp;examined the relationship between psychopathological symptoms and (dis-)continuation of drug treatment for ADHD showing\u0026nbsp;mixed findings.\u0026nbsp;Atzori and colleagues\u0026nbsp;(27)\u0026nbsp;retrospectively compared 134 patients referring to the Centre for Pharmacological Therapies in Children and Adolescents Psychiatry (Cagliari, Italy) between 1998 and 2005, and taking methylphenidate with at least three years of follow-up. The presence of comorbidity (besides the significant effects of younger age, being female and not living with both parents) predicted continuation of therapy at three years. On the other hand, the absence of comorbidity (besides the significant effect of older age) was associated with therapy discontinuation due to functional remission. Finally, discontinuing therapy for other reasons (e.g., poor compliance, reduction of efficacy) was not associated with comorbidity whereas it was associated with older age when starting therapy and hyperactive subtype of ADHD\u0026nbsp;(27). The relationship between psychiatric comorbidity and persistence of ADHD therapy has been confirmed\u0026nbsp;by a retrospective study using Korean Health Insurance data from 2007 to\u0026nbsp;2011\u0026nbsp;(40). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOther studies who did not differentiate between reasons for discontinuing ADHD therapy (i.e., remission vs other reasons) showed no association between therapy continuation and psychopathology. For example, Palli et al.\u0026nbsp;(36)\u0026nbsp;did not find evidence of an association between continuation of ADHD therapy and comorbid psychopathology using Medicaid Analytic eXtract data from Texas, New York, California and Illinois (United States) between 2003 to 2005. Whereas continuation of ADHD therapy was associated with prescriptions of other psychotropic drug classes (other than stimulants). These findings could be explained considering that multivariate models were fitted including both comorbid psychopathologies and drugs usually used to treat them. Thus, it is possible that the significant effect of other psychotropic drug classes masked or mediated the effect of the association between comorbid psychopathology and continuation of ADHD therapy. Further, the association observed may be due to clinical severity of cases taking multiple medications despite the effects of other important factors (i.e., number of comorbidities, recent mental health-related hospitalization) were controlled in the analyses. Another explanation for the study findings points to the possible effect of the propensity to assume medications that would lead to an association between the continuation of ADHD pharmacotherapy and prescriptions of other psychotropic drugs. In accordance with the latter explanation, Safavi et al.\u0026nbsp;(41)\u0026nbsp;showed that comorbidity was not associated with adherence to ADHD pharmacotherapy in 118 children with ADHD who referred to a child psychiatry clinic in Iran in 2018. Whereas ADHD children with a family history of psychotropic medication use reported higher adherence to ADHD pharmacotherapy compared to those with no family history\u0026nbsp;(41). Similarly, another study\u0026nbsp;(42)\u0026nbsp;conducted with fifty children referring to a tertiary care center in Mumbai (India) did not find evidence of associations between adherence to ADHD pharmacotherapy and conduct disorder, oppositional defiant disorder and emotional problems. Whereas adherence correlated negatively with the severity of ADHD. A recent study\u0026nbsp;(43)\u0026nbsp;analyzing adherence to methylphenidate in Japan using retrospective data demonstrated no association between adherence and concomitant use of antipsychotic, antidepressants and anxiolytics. Finally, Cheung et al.\u0026nbsp;(44)\u0026nbsp;reported no significant univariate association between methylphenidate treatment adherence at two years and the five Diagnostic and Statistical Manual of Mental Disorders - oriented scales of the Child Behavior Checklist (CBCL), and symptoms of ADHD, in a sample of \u0026nbsp;264 children in the Netherlands. \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eStudy aims and hypotheses\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe first aim of this study was to present demographic and clinical characteristics of children and adolescent aged 5 to 17 years who received drugs treatment for ADHD at the reference center Scientific Institute IRCCS \u0026ldquo;E. Medea\u0026rdquo; (Brindisi, Italy) between\u0026nbsp;January, 2013 and May, 2022.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe second aim of the study was to increase scientific knowledge on the association between (dis-)continuation of ADHD pharmacotherapy, demographic and clinical characteristics, in particular symptoms of psychopathology when initiating ADHD pharmacotherapy. Considering previous mixed findings on the relationship between treatment (dis-)continuation and psychopathology, the study was exploratory in nature and we expected higher psychopathology in patients who continued pharmacotherapy compared to those who did not it (27,40) or no between group difference (36,41\u0026ndash;44).\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003eParticipants and procedure\u003c/h2\u003e\n\u003cp\u003eThis retrospective study included children and adolescents between 6 and 17 years old referring to one (Scientific Institute IRCCS \u0026ldquo;E. Medea\u0026rdquo; in Brindisi, Italy) of the Puglia reference prescription centers for ADHD pharmacological treatment between January, 2013 and May, 2022. Prescription centers confirm the ADHD diagnosis and establish the pharmacological therapy monitoring it overtime. According to the resolution no. 1242 by the Puglia Regional Council, 26 July 2007 (DGR. 1242/2007), five reference prescription centers were accredited as centers specialized in diagnosis and treatment of ADHD\u0026nbsp;(45). In December 13, 2016, regional prescription centers were increased to eight (DGR. 2036/2016). Patients were included in this study if they were enrolled in the Italian National Registry for ADHD and received a prescription for methylphenidate (MPH) from the reference center Scientific Institute IRCCS \u0026ldquo;E. Medea\u0026rdquo; in Brindisi (Italy).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWritten informed consent for medication\u0026nbsp;administration and analysis of clinical data\u0026nbsp;for scientific research was obtained from both parents and patients. The first drug administration, the \u0026ldquo;testing dose\u0026rdquo; (5 mg of immediate-release methylphenidate) takes place at the Scientific Institute during hospitalization in order to monitor potential side effects and vital signs (e.g., brain and cardiac activity). In absence of relevant side effects, patients started chronic treatment with modified-release methylphenidate and a first follow-up at one-month. Drug dose for modified-release methylphenidate ranges from 0.3 to 0.5 mg/kg until a total maximum of 60 mg/die administered in a unique dose. For some patients, 5 mg of immediate-release methylphenidate is also administered in the afternoon in order to help patients in completing homework assignments. Drug dose is based on improvement in child behavior and psychosocial functioning. An annual \u0026ldquo;drug holiday\u0026rdquo; period (approximately of two/three months) during summer vacation takes place for the majority of patients and according to their symptomatology. It is planned in order to decrease the effects of medication on height and weight as well as to assess the need for continuing medication during the first month(s) of the new school academic year. The research was approved by\u0026nbsp;the local ethical committee of the \u0026ldquo;Research Ethics Committee \u0026ndash; IRCCS Istituto Tumori Giovanni Paolo II - Bari (Italy).\u0026rdquo;\u003c/p\u003e\n\u003cp\u003eInstruments\u003c/p\u003e\n\u003cp\u003eThe following demographic and clinical data was obtained from the Registry for ADHD and medical records: age at treatment initiation, sex, city of residence, months between diagnosis and pharmacotherapy, months of pharmacotherapy, quotient of intelligence (QI), ADHD diagnosis subtype, comorbidity and pharmacological treatment status. Pharmacological treatment status was defined as \u0026ldquo;in treatment\u0026rdquo; and \u0026ldquo;treatment discontinuation\u0026rdquo; as at May, 2022, for participants for which at least 12 months of follow-up after the first pharmacological administration for ADHD were available.\u003c/p\u003e\n\u003cp\u003eThe Child Behavior Checklist (CBCL/6\u0026ndash;18)\u0026nbsp;(46,47)\u0026nbsp;was used to explore emotional and behavioural symptoms, competencies and adaptive functioning as reported by parents. Items are scored on a three-point scale (0 = not true, 1 = somewhat or sometimes true, and 2 = very or often true) and refer to symptoms presentation during the preceding\u0026nbsp;six\u0026nbsp;months. Internalizing and externalizing broad band symptoms dimensions were empirically developed from the CBCL\u0026nbsp;(Achenbach \u0026amp; Rescorla, 2000). All CBCL scales have a T-score mean of 50 and standard deviation of 10 and different norms are provided for each gender across different age ranges. Previous research showed the usefulness of syndrome scales for a complete and accurate assessment of young patients\u0026nbsp;(48\u0026ndash;50). The most recent CBCL completed before the first methylphenidate administration was analysed.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cp\u003eDescriptive statistics (number, frequency, mean and standard deviation) were computed to explore the characteristics of the sample and of subgroups according to pharmacological treatment status. Subgroup analysis based on pharmacological treatment status included participants (n= 63) for which at least 12 months of follow-up after the first pharmacological administration for ADHD were available at May 2022.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBetween group differences according to pharmacological treatment status were analyzed using the Chi-square test and student-t statistics\u0026nbsp;for group comparison on categorical and continuous variables, using Cramer\u0026rsquo;s V and Cohen\u0026rsquo;s d as estimate of effect size, respectively. When the assumption on equality of variance (tested using Levene\u0026rsquo;s test) was violated (p\u0026lt; 0.05 or approaching significance at p\u0026lt; 0.10) Welch homogeneity correction was applied. Interpretation of effect size for Cramer\u0026rsquo;s V were moderate if between .2 and .6, and strong if higher than 0.6, whereas, for Cohen\u0026rsquo;s d, moderate if between .5 and .8, and strong if higher than .8.\u003c/p\u003e\n\u003cp\u003eSubsequently, two multivariable logistic regression models were used to test associations between pharmacological treatment status and variables of interest (\u003cem\u003emodel 1\u003c/em\u003e) and\u0026nbsp;psychopathology\u0026nbsp;as measured by the CBCL subscales (\u003cem\u003emodel 2\u003c/em\u003e),\u0026nbsp;including variables whose\u0026nbsp;bivariate associations were significant (p\u0026lt; 0.05) or approaching significance (p\u0026lt; 0.10) based on subgroup analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eModel 2 included only participants (n= 40) for which the CBCL was available. Indeed, CBCL data\u0026nbsp;was not available for all children and adolescents. Specifically, some of them have been previously evaluated for ADHD receiving the diagnosis by medical doctors specialized in child and adolescent neuropsychiatry to subsequently refer to the Scientific Institute IRCCS \u0026ldquo;E. Medea\u0026rdquo; for the first prescription of the ADHD pharmacological therapy and its monitoring overtime. Usually, for those patients, a new diagnostic assessment is not implemented. As a preliminary analysis, differences between participants, whose data was considered for the subgroup comparisons, with (n= 40) and without (n= 23) CBCL evaluation were explored showing no difference in demographic and clinical characteristics.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll analysis were performed using JASP version 0.16.0.0\u0026nbsp;(51)\u0026nbsp;and \u003cem\u003ep\u003c/em\u003e value \u0026lt; 0.05 was considered to be significant.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eADHD was diagnosed at a mean of 8.8 years of age (Table 1). Eight months generally occurred between diagnosis and pharmacotherapy initiation. 26% of patients lived in the same city as Scientific Institute location (i.e., Brindisi) whereas the rest lived in other Apulia provinces (i.e., 37.7% in Lecce, 20.8% in Taranto, 11.7% in Bari, 3.9% in other provinces).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe majority (92%) of patients were diagnosed with combined type of ADHD, 6.5% with the inattentive type and only one (1.3%) with the hyperactive one.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e77% of patients showed one or more comorbid disorder as follows: 54.6% one, 19.5% two, 1.3% three and 1.3% four disorders in comorbidity, respectively. The most frequent comorbid conditions were disruption and impulse control disorders,\u0026nbsp;intellectual and learning disability.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNear all patients (97.4%) received at least one form of treatment other than pharmacotherapy. Specifically, 52% of patients received one other treatment, 44.2% two and 1.3% three other treatments. The most frequent treatments provided were cognitive-behavioral therapy and parent training.\u003c/p\u003e\n\u003cp\u003e[insert table 1 about here]\u003c/p\u003e\n\u003ch2\u003eBivariate associations\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003e63 of 77 patients had at least 12 months of follow-up after the first pharmacological administration for ADHD as at May 2022. Of these, 14 (22.2%) patients discontinued ADHD pharmacotherapy. As expected these two groups differed on total months in pharmacotherapy for ADHD (Table 1). On the contrary, no significant difference was observed for age at diagnosis and age at the first assumption of pharmacotherapy for ADHD, diagnosis, comorbidity and other treatments. Further, patients in treatment showed a higher QI mean score than patients who discontinued treatment (borderline significant p value of 0.091).\u003c/p\u003e\n\u003cp\u003eConsidering between groups comparisons on the CBCL, differences on the externalizing and rule breaking behavior subscales were borderline significant (p= 0.075 and p= 0.053, respectively) with higher symptoms in patients who discontinued compared to those that continued ADHD pharmacotherapy (Table 2). Further, patients who discontinued ADHD pharmacotherapy showed a significantly (p= 0.047) higher mean T total score compared to patients who continued treatment.\u003c/p\u003e\n\u003cp\u003e[insert table 2 about here]\u003c/p\u003e\n\u003ch2\u003eLogistic regression of associations with ADHD pharmacotherapy status\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eConsidering demographic and clinical characteristics, no significant bivariate association was observed between pharmacological status and variables of interest with the exception of a trend for significant association with QI. Thus, model 1 was no longer analyzed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn order to test model 2, bivariate associations were computed considering only participants with CBCL data (n= 40). Patients in treatment were significantly (\u0026chi;\u0026sup2; (1)= 3.971, p= 0.046, Cramer\u0026rsquo;s V= .32) less likely to show intellectual disability (14.7%, n= 5) compared to those who discontinued treatment (50%, n= 3) whereas no other difference was shown for demographic and clinical data. Thus, model 2 included intellectual disability and rule-breaking behavior CBCL subscale. The results of the model are shown in Table 3 and demonstrated significant associations between pharmacotherapy status and rule-breaking behavior (p= 0.032), and intellectual disability (p= 0.028).\u003c/p\u003e\n\u003cp\u003e[insert table 3 about here]\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eFindings of the present study demonstrated that one in five (n= 14, 22% of patients with at least one year follow-up) young patients discontinued ADHD pharmacotherapy after a mean of 12 months of pharmacotherapy (SD= 14.2), whereas the rest (n= 49, 78%) has continued using medication for a mean period of 51 months (SD= 25.3). This finding is consistent with the scientific literature on the topic\u0026nbsp;(27,28,30). A previous study\u0026nbsp;(22)\u0026nbsp;conducted with a large Italian sample of children and adolescents with ADHD showed that\u0026nbsp;21.5% of patients interrupted treatment after two/four months of pharmacotherapy due to decision of parents/health professional, adverse events, lost to follow-up, ineffectiveness and other reasons.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsidering group differences according to pharmacological treatment status, a trend for group difference for QI was present for which patients in treatment showed a higher QI mean score than patients who discontinued treatment. On the other hand, no significant difference was observed for age at diagnosis, age at the first assumption of pharmacotherapy for ADHD and other demographic characteristics, diagnosis, comorbidity and other treatments. Further, considering the subsample (N= 40) with data at the CBCL, intellectual disability and rule-breaking behavior were associated with pharmacological treatment status. Patients with high rule-breaking behavior and intellectual disability were more likely to discontinuing ADHD drug treatment. These findings were unexpected since previous studies mainly showed no difference between groups\u0026nbsp;(36,41\u0026ndash;44)\u0026nbsp;or that comorbid disorders predicted treatment continuation\u0026nbsp;(27,40). However, Nayak et al.\u0026nbsp;(42)\u0026nbsp;have recently found evidence that\u0026nbsp;adherence negatively correlates with the severity of ADHD. Between studies differences may be accounted by differences in sample and methodology. Masi et al.\u0026nbsp;(52)\u0026nbsp;have recently highlighted that intellectual disability increases the risk of any adverse event, especially irritability, suggesting that it may be linked to low tolerability to drug treatment. On the other hand, Nayak et al.\u0026nbsp;(42)\u0026nbsp;showed that when controlling for the presence of side effects, the association between ADHD severity and poor adherence became non-significant. It follows that intellectual disability and rule-breaking behavior may interact with side effects with these patients experiencing relevant increase in irritability with drug treatment\u0026nbsp;(53), or they could experience side effects as more distressing, both leading to treatment discontinuation. An alternative explanation concerns the fact that these patients may be less compliant to treatment and/or that their family may experience relevant difficulty in their management leading to treatment interruption. Furthermore, according to our clinical experience, patients with intellectual disability and their families may have high or unrealistic expectations on ADHD pharmacotherapy in improving overall cognitive functioning. Therefore, they may be at higher risk of discontinuing treatment, at least in our sample. Finally, patients with high symptoms of rule-breaking behavior could experience pharmacotherapy as negatively affecting their personality or that medications take away their personality changing the way they perceive themselves. Thus, treatment discontinuation may also be related to the relationship between medication, behavior and identity. However, the association between treatment status and disruption and impulse control disorders was not significant. Taken all together, our findings add knowledge on the association between psychopathology and treatment (dis-)continuation proposing potential explanations. Studies with large samples are needed to support our findings and clarify the relationship\u0026nbsp;between psychopathology and treatment (dis-)continuation using both dimensional and categorical approaches, and controlling for important covariates. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eLimitations of the study\u003c/h2\u003e\n\u003cp\u003eThe study was conducted with a population of participants from a delimited geographic and cultural area, that is, one ADHD reference center located in a region of South Italy. As a consequence, the results may not be generalized to other different populations or settings. The retrospective design of the study and the small sample size may also limit their generalizability. Further, the data analysed were collected as part of the ADHD clinical routine management rather than for specific research purposes. Finally, information on patients\u0026rsquo; reasons for treatment discontinuation were missing because patients were lost to follow-up, limiting results interpretation. The lack of data on reasons for discontinuation, parental/family and social characteristics may limit the interpretability of our findings since adherence in young people could be determined or at least influenced by these factors (28,42,44). As a consequence, our findings should be interpreted considering the above limitations. Despite these limitations, the present study included data from patients encountered in a clinical setting incorporating real-life variability in symptoms of psychopathology at presentation (without the application of exclusion criteria) supporting its ecological validity.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe findings of the present study showed that patients who discontinued treatment showed higher frequency of intellectual disability and higher rule-breaking behaviour, before the first pharmacological administration for ADHD, compared to patients who continued treatment. Our findings highlight the need of periodical assessment monitoring difficulties with (or reasons for poor) treatment compliance as well as side effects in order to provide individualized care. \u003c/p\u003e\n"},{"header":"Abbreviations","content":"\u003cp\u003eADHD: Attention-Deficit/Hyperactivity Disorder\u003c/p\u003e\n\u003cp\u003eCBCL: Child Behavior Checklist.\u003c/p\u003e\n\u003cp\u003eQI: quotient of intelligence.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll methods were carried out in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The research was approved by\u0026nbsp;the local ethical committee of the \u0026ldquo;Research Ethics Committee \u0026ndash; IRCCS Istituto Tumori Giovanni Paolo II - Bari (Italy).\u0026rdquo;\u0026nbsp;\u0026nbsp;Written informed consent for medication administration and analysis of clinical data for scientific research was obtained from both parents and patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for medication administration and analysis of clinical data for scientific research was obtained from both parents and patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare to have no competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo funding was received for this specific study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e Conceptualization, S.A. and A.T.; methodology and formal analysis, S.A.; sample recruitment, I.F. and M.D.R.; investigation, I.F. and A.T.; data curation, I.F., S.S. and S.A.; writing - original draft preparation, S.A. and A.T.; supervision, A.T. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Italian Ministry of health RC 2018-2020.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAmerican Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA; 2013.\u003c/li\u003e\n \u003cli\u003eFaraone SV, Banaschewski T, Coghill D, Zheng Y, Biederman J, Bellgrove MA, et al. The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder. Neurosci Biobehav Rev. 2021;128:789\u0026ndash;818.\u003c/li\u003e\n \u003cli\u003eWillcutt EG. The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics. 2012;9(3):490\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eArnold LE, Hodgkins P, Kahle J, Madhoo M, Kewley G. Long-Term Outcomes of ADHD: Academic Achievement and Performance. J Atten Disord. 2020;24(1):73\u0026ndash;85.\u003c/li\u003e\n \u003cli\u003eCraig F, Savino R, Fanizza I, Lucarelli E, Russo L, Trabacca A. A systematic review of coping strategies in parents of children with attention deficit hyperactivity disorder (ADHD). Research in Developmental Disabilities. 2020;98:103571.\u003c/li\u003e\n \u003cli\u003eMcQuade JD, Breaux R, Mordy AE, Taubin D. Childhood ADHD Symptoms, Parent Emotion Socialization, and Adolescent Peer Problems: Indirect Effects Through Emotion Dysregulation. J Youth Adolesc. 2021;50(12):2519\u0026ndash;32.\u003c/li\u003e\n \u003cli\u003ePowell V, Riglin L, Hammerton G, Eyre O, Martin J, Anney R, et al. What explains the link between childhood ADHD and adolescent depression? Investigating the role of peer relationships and academic attainment. Eur Child Adolesc Psychiatry. 2020;29(11):1581\u0026ndash;91.\u003c/li\u003e\n \u003cli\u003eSigfusdottir ID, Asgeirsdottir BB, Hall HA, Sigurdsson JF, Young S, Gudjonsson GH. An epidemiological study of ADHD and conduct disorder: does family conflict moderate the association? Soc Psychiatry Psychiatr Epidemiol. 2017;52(4):457\u0026ndash;64.\u003c/li\u003e\n \u003cli\u003eSharp W, Mangalmurti A, Hall C, Choudhury S, Shaw P. Associations between neighborhood, family factors and symptom change in childhood attention deficit hyperactivity disorder. Soc Sci Med. 2021;271:112203.\u003c/li\u003e\n \u003cli\u003eTung I, Li JJ, Meza JI, Jezior KL, Kianmahd JSV, Hentschel PG, et al. Patterns of Comorbidity Among Girls With ADHD: A Meta-analysis. Pediatrics. 2016;138(4):e20160430.\u003c/li\u003e\n \u003cli\u003eReale L, Bartoli B, Cartabia M, Zanetti M, Costantino MA, Canevini MP, et al. Comorbidity prevalence and treatment outcome in children and adolescents with ADHD. Eur Child Adolesc Psychiatry. 2017;26(12):1443\u0026ndash;57.\u003c/li\u003e\n \u003cli\u003eZenglein Y, Schwenck C, Westerwald E, Schmidt C, Beuth S, Meyer J, et al. Empirically Determined, Psychopathological Subtypes in Children With ADHD. J Atten Disord. 2016;20(2):96\u0026ndash;107.\u003c/li\u003e\n \u003cli\u003eJensen PS, Hinshaw SP, Kraemer HC, Lenora N, Newcorn JH, Abikoff HB, et al. ADHD comorbidity findings from the MTA study: comparing comorbid subgroups. J Am Acad Child Adolesc Psychiatry. 2001;40(2):147\u0026ndash;58.\u003c/li\u003e\n \u003cli\u003eReale L, Bonati M. ADHD prevalence estimates in Italian children and adolescents: a methodological issue. Ital J Pediatr. 2018;44(1):108.\u003c/li\u003e\n \u003cli\u003eSociet\u0026agrave; Italiana di Neuropsichiatria dell\u0026rsquo;Infanzia e dell\u0026rsquo;Adolescenza. Linee-guida per la diagnosi e la terapia farmacologica del Disturbo da Deficit Attentivo con Iperattivit\u0026agrave; (ADHD) in et\u0026agrave; evolutiva. Approvazione CD: 24 giugno 2002. 2002 [Accessed April 22, 2022]. Available at: http://sinpia.eu/linee-guida-3/\u003c/li\u003e\n \u003cli\u003eAgenzia Italiana del Farmaco. Protocollo diagnostico e terapeutico della sindrome di iperattivita e deficit di attenzione per il registro nazionale ADHD (all. 1 - art. 1). Gazzetta Ufficiale Serie Generale n.95 del 24-04-2007 - Suppl. Ordinario n. 106. 2007;\u003c/li\u003e\n \u003cli\u003ePanei P, Arcieri R, Vella S, Bonati M, Martini N, Zuddas A. Italian attention-deficit/hyperactivity disorder registry. Pediatrics. 2004;114(2):514.\u003c/li\u003e\n \u003cli\u003ePanei P, Kneiiwoif AL, Bonati M, Masi G, Zuddas A, Costantino A, et al. Psychotropic Drug Used for Attention-Deficit/Hyperactivity Disorder (ADHD) in Italian Children and Adolescent Population. Drug-Safety. 2008;31(10):885\u0026ndash;885.\u003c/li\u003e\n \u003cli\u003ePanei P, Arcieri R, Bonati M, Bugarini M, Didoni A, Germinario E. Safety of psychotropic drug prescribed for attention-deficit/hyperactivity disorder in Italy. Adverse Drug Reaction Bulletin. 2010;(260):999\u0026ndash;1002.\u003c/li\u003e\n \u003cli\u003eConrad P, Bergey MR. The impending globalization of ADHD: Notes on the expansion and growth of a medicalized disorder. Social Science \u0026amp; Medicine. 2014;122:31\u0026ndash;43.\u003c/li\u003e\n \u003cli\u003eMaschietto D, Baioni E, Vio C, Novello F, Germinario E, Regini F, et al. Prevalenza dell\u0026rsquo;ADHD in una popolazione pediatrica e sua esposizione al trattamento psico\u0026ndash;comportamentale e farmacologico. Medico e Bambino. 2012;XV(10):667.\u003c/li\u003e\n \u003cli\u003ePanei P, Arcieri R. Il registro dell\u0026rsquo;ADHD: valutazione post-marketing del profilo beneficio-rischio dei farmaci e promozione dell\u0026rsquo;appropriatezza. Recenti Progressi in Medicina. 2013;104(6):254\u0026ndash;61.\u003c/li\u003e\n \u003cli\u003eReale L, Zanetti M, Cartabia M, Fortinguerra F, Bonati M, Adhd a nome GRL. Due anni di attivit\u0026agrave; del Registro ADHD della Regione Lombardia: analisi dei percorsi di cura diagnostici e terapeutici. Ricerca \u0026amp; Pratica. 2014;30(5):198\u0026ndash;211.\u003c/li\u003e\n \u003cli\u003eBonati M, Reale L, Zanetti M, Cartabia M, Fortinguerra F, Capovilla G, et al. A Regional ADHD Center-Based Network Project for the Diagnosis and Treatment of Children and Adolescents With ADHD. J Atten Disord. 2018;22(12):1173\u0026ndash;84.\u003c/li\u003e\n \u003cli\u003eBonati M, Scarpellini F, Cartabia M, Zanetti M, on behalf of the Lombardy ADHD Group. Ten Years (2011\u0026ndash;2021) of the Italian Lombardy ADHD Register for the Diagnosis and Treatment of Children and Adolescents with ADHD. Children. 2021;8(7):598.\u003c/li\u003e\n \u003cli\u003eOerbeck B, Furu K, Zeiner P, Aase H, Reichborn-Kjennerud T, Pripp AH, et al. Child and Parental Characteristics of Medication Use for Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2020;30(7):456\u0026ndash;64.\u003c/li\u003e\n \u003cli\u003eAtzori P, Usala T, Carucci S, Danjou F, Zuddas A. Predictive factors for persistent use and compliance of immediate-release methylphenidate: a 36-month naturalistic study. J Child Adolesc Psychopharmacol. 2009;19(6):673\u0026ndash;81.\u003c/li\u003e\n \u003cli\u003eAhmed R, Aslani P. Attention-deficit/hyperactivity disorder: an update on medication adherence and persistence in children, adolescents and adults. Expert Rev Pharmacoecon Outcomes Res. 2013;13(6):791\u0026ndash;815.\u003c/li\u003e\n \u003cli\u003eBhang SY, Hwang JW, Kwak YS, Joung YS, Lee S, Kim B, et al. Differences in Utilization Patterns among Medications in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: a 36-Month Retrospective Study Using the Korean Health Insurance Review and Assessment Claims Database. J Korean Med Sci. 2016;31(8):1284\u0026ndash;91.\u003c/li\u003e\n \u003cli\u003eLachaine J, Beauchemin C, Sasane R, Hodgkins PS. Treatment patterns, adherence, and persistence in ADHD: a Canadian perspective. Postgrad Med. 2012;124(3):139\u0026ndash;48.\u003c/li\u003e\n \u003cli\u003eCatal\u0026aacute;-L\u0026oacute;pez F, Hutton B, N\u0026uacute;\u0026ntilde;ez-Beltr\u0026aacute;n A, Page MJ, Ridao M, Mac\u0026iacute;as Saint-Gerons D, et al. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials. PLoS One. 2017;12(7):e0180355.\u003c/li\u003e\n \u003cli\u003eFrank E, Ozon C, Nair V, Othee K. Examining why patients with attention-deficit/hyperactivity disorder lack adherence to medication over the long term: a review and analysis. J Clin Psychiatry. 2015;76(11):e1459-1468.\u003c/li\u003e\n \u003cli\u003eGajria K, Lu M, Sikirica V, Greven P, Zhong Y, Qin P, et al. Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder - a systematic literature review. Neuropsychiatr Dis Treat. 2014;10:1543\u0026ndash;69.\u003c/li\u003e\n \u003cli\u003eGau SSF, Chen SJ, Chou WJ, Cheng H, Tang CS, Chang HL, et al. National survey of adherence, efficacy, and side effects of methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan. J Clin Psychiatry. 2008;69(1):131\u0026ndash;40.\u003c/li\u003e\n \u003cli\u003eKhan MU, Aslani P. A Review of Factors Influencing the Three Phases of Medication Adherence in People with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2019;29(6):398\u0026ndash;418.\u003c/li\u003e\n \u003cli\u003ePalli SR, Kamble PS, Chen H, Aparasu RR. Persistence of stimulants in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2012;22(2):139\u0026ndash;48.\u003c/li\u003e\n \u003cli\u003eStoreb\u0026oslash; OJ, Pedersen N, Ramstad E, Kielsholm ML, Nielsen SS, Krogh HB, et al. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies. Cochrane Database Syst Rev. 2018;5:CD012069.\u003c/li\u003e\n \u003cli\u003eWang LJ, Yang KC, Lee SY, Yang CJ, Huang TS, Lee TL, et al. Initiation and Persistence of Pharmacotherapy for Youths with Attention Deficit Hyperactivity Disorder in Taiwan. PLoS One. 2016;11(8):e0161061.\u003c/li\u003e\n \u003cli\u003eWong ICK, Asherson P, Bilbow A, Clifford S, Coghill D, DeSoysa R, et al. Cessation of attention deficit hyperactivity disorder drugs in the young (CADDY)--a pharmacoepidemiological and qualitative study. Health Technol Assess. 2009;13(50):iii\u0026ndash;iv, ix\u0026ndash;xi, 1\u0026ndash;120.\u003c/li\u003e\n \u003cli\u003eBhang SY, Kwack YS, Joung YS, Lee SI, Kim B, Sohn SH, et al. Factors that Affect the Adherence to ADHD Medications during a Treatment Continuation Period in Children and Adolescents: A Nationwide Retrospective Cohort Study Using Korean Health Insurance Data from 2007 to 2011. Psychiatry Investig. 2017;14(2):158\u0026ndash;65.\u003c/li\u003e\n \u003cli\u003eSafavi P, Saberzadeh M, Tehrani AM. Factors Associated with Treatment Adherence in Children with Attention Deficit Hyperactivity Disorder. Indian J Psychol Med. 2019;41(3):252\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eNayak AS, Nachane HB, Keshari P, Parkar SR, Saurabh KH, Arora M. Prescription patterns and medication adherence in preadolescent children with attention deficit hyperactivity disorder. Indian Journal of Psychiatry. 2021;63(3):274\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eIshizuya A, Enomoto M, Tachimori H, Takahashi H, Sugihara G, Kitamura S, et al. Risk factors for low adherence to methylphenidate treatment in pediatric patients with attention-deficit/hyperactivity disorder. Sci Rep. 2021;11(1):1707.\u003c/li\u003e\n \u003cli\u003eCheung K, Dierckx B, El Marroun H, Hillegers MHJ, Stricker BH, Visser LE. Methylphenidate Treatment Adherence and Persistence in Children in the Netherlands. J Child Adolesc Psychopharmacol. 2021;31(3):205\u0026ndash;13.\u003c/li\u003e\n \u003cli\u003eGerminario EAP, Arcieri R, Marzi M, Panei P, Vella S. Registro nazionale ADHD (Attention-Deficit/Hyperactivity Disorder): dati dal 2007 al 2016. (Rapporti ISTISAN 16/37). Roma: Istituto Superiore di Sanit\u0026agrave;; 2016.\u003c/li\u003e\n \u003cli\u003eAchenbach T, Rescorla L. Manual for the ASEBA (Achenbach System of Empirically Based Assessment) Preschool Forms \u0026amp; Profiles. Burlington: University of Vermont, Research Center for Children, Youth, \u0026amp; Families; 2000.\u003c/li\u003e\n \u003cli\u003eFrigerio A, Cattaneo C, Cataldo M, Schiatti A, Molteni M, Battaglia M. Behavioral and Emotional Problems Among Italian Children and Adolescents Aged 4 to 18 Years as Reported by Parents and Teachers. European Journal of Psychological Assessment. 2004;20(2):124\u0026ndash;33.\u003c/li\u003e\n \u003cli\u003eBellina M, Brambilla P, Garzitto M, Negri GAL, Molteni M, Nobile M. The ability of CBCL DSM-oriented scales to predict DSM-IV diagnoses in a referred sample of children and adolescents. Eur Child Adolesc Psychiatry. 2013;22(4):235\u0026ndash;46.\u003c/li\u003e\n \u003cli\u003eIvanova MY, Achenbach TM, Dumenci L, Rescorla LA, Almqvist F, Weintraub S, et al. Testing the 8-Syndrome Structure of the Child Behavior Checklist in 30 Societies. Journal of Clinical Child \u0026amp; Adolescent Psychology. 2007;36(3):405\u0026ndash;17.\u003c/li\u003e\n \u003cli\u003eNobile M, Colombo P, Bellina M, Molteni M, Simone D, Nardocci F, et al. Psychopathology and adversities from early- to late-adolescence: a general population follow-up study with the CBCL DSM-Oriented Scales. Epidemiology and Psychiatric Sciences. 2013;22(1):63\u0026ndash;73.\u003c/li\u003e\n \u003cli\u003eJASP Team. JASP (Version 0.16.3)[Computer software]. 2022.\u003c/li\u003e\n \u003cli\u003eMasi G, Pfanner C, Liboni F, Lenzi F, Villafranca A, D\u0026rsquo;Acunto G, et al. Acute Tolerability of Methylphenidate in Treatment-Na\u0026iuml;ve Children with ADHD: An Analysis of Naturalistically Collected Data from Clinical Practice. Pediatr Drugs. 2022;24(2):147\u0026ndash;54.\u003c/li\u003e\n \u003cli\u003eWigal T, Greenhill L, Chuang S, McGOUGH J, Vitiello B, Skrobala A, et al. Safety and Tolerability of Methylphenidate in Preschool Children With ADHD. Journal of the American Academy of Child \u0026amp; Adolescent Psychiatry. 2006;45(11):1294\u0026ndash;303.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Demographic and clinical characteristics of total sample and pharmacological treatment status subgroups.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003eTotal sample\u003c/p\u003e\n \u003cp\u003e(N= 77)\u003c/p\u003e\n \u003cp\u003eM (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003eIn treatment\u003c/p\u003e\n \u003cp\u003e(n= 49)\u003c/p\u003e\n \u003cp\u003eM (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003eTreatment discontinuation\u003c/p\u003e\n \u003cp\u003e(n= 14)\u003c/p\u003e\n \u003cp\u003eM (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e\u003cem\u003et / \u0026chi;\u0026sup2;\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e(df)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003eCohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e / Cramer\u0026rsquo;s \u003cem\u003eV\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eAge,\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e9.5 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e9.3 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e10.2 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e-1.213 (61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eMales,\u003cem\u003e\u0026nbsp;n (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e66 (85.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e43 (87.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e12 (85.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e0.041 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eAge at diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e8.8 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e8.6 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e9.2 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e-0.775 (61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eMonths between diagnosis and pharmacotherapy \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e8.4 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e7.4 (11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e11.9 (15.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e-1.046 (17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eMonths of pharmacotherapy \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e36.3 (28.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e50.8 (25.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e12.2 (14.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e7.361 (38.61) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e1.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eASL of residence\u0026nbsp;in the same city as Scientific Institute location,\u003cem\u003e\u0026nbsp;n (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e20 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e13 (26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e3 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e0.150 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003e\u003cem\u003eDiagnosis, n (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e1.552 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eADHD-C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e71 (92.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e44 (89.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e14 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eADHD-H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e1 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eADHD-I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e5 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e5 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003e\u003cem\u003eComorbidity, n (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eOne or more\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e59 (76.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e37 (75.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e10 (71.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e0.096 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eAutism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e4 (5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e3 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e1 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e0.019 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eIntellectual disability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e16 (20.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e8 (16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e4 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e1.059 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eLearning disability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e16 (20.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e11 (22.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e4 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e0.225 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eLanguage disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e7 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e7 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e2.25 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eEmotional disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e6 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e5 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e1.552 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eDisruption and impulse control disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e16 (20.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e7 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e3 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e0.416 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eEpilepsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e1 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e1 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eMigraine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e1 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e1 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eDevelopmental coordination disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e4 (5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e2 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e2 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e1.907 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eCongenital abnormalities non specified and chromosomal abnormalities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e5 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e3 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e1 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e0.019 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eAbnormal EEG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e3 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e3 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e0.9 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eQI \u003csup\u003ea\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e81.1 (19.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e83.4 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e70.6 (20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e1.728 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003e\u003cem\u003eOther treatment, n (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eOne or more\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e75 (97.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e48 (98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e13 (92.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e0.922 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eCounselling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e1 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eParent training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e37 (48.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e22 (44.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e4 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e1.198 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eCognitive-behavioral therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e69 (89.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e45 (91.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e12 (85.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e0.474 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eChild training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003ePsychodynamic psychotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eFamily therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.57660167130919%\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e4 (5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.484679665738161%\"\u003e\n \u003cp\u003e4 (8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.623955431754874%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.991643454038996%\"\u003e\n \u003cp\u003e1.22 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.838440111420613%\"\u003e\n \u003cp\u003e.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eNote\u003c/em\u003e. The sum of patients of \u0026ldquo;in treatment\u0026rdquo; and \u0026ldquo;treatment discontinuation\u0026rdquo; groups does not equal that of patients of total sample since not all patients was included in subgroup analysis. \u0026nbsp;\u003cem\u003e\u003csup\u003ea\u003c/sup\u003e:\u003c/em\u003e data available for 58 patients totally and for 47 in group comparison. \u003cem\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/em\u003e\u003cem\u003e:\u003c/em\u003e Welch homogeneity correction was applied. \u003cem\u003eM:\u003c/em\u003e mean, \u003cem\u003eSD:\u003c/em\u003e standard deviation, \u003cem\u003eASL:\u003c/em\u003e local Health Service office, \u003cem\u003eADHD-C:\u003c/em\u003e attention deficit/hyperactivity disorder combined type, \u003cem\u003eADHD-H:\u003c/em\u003e attention-deficit/hyperactivity disorder hyperactive type, \u003cem\u003eADHD-I\u003c/em\u003e: attention-deficit=hyperactivity disorder inattentive type,\u003cem\u003e\u0026nbsp;QI\u003c/em\u003e: quotient of intelligence.\u0026nbsp;* p\u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e. CBCL subscales\u0026rsquo; mean T scores of total sample and pharmacological treatment status subgroups.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003eTotal sample \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e(n= 50)\u003c/p\u003e\n \u003cp\u003eM (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003eIn treatment\u003c/p\u003e\n \u003cp\u003e(n= 34)\u003c/p\u003e\n \u003cp\u003eM (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003eTreatment discontinuation\u003c/p\u003e\n \u003cp\u003e(n= 6)\u003c/p\u003e\n \u003cp\u003eM (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e (df)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003eCohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eActivities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e29.7 (9.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e29.9 (11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e29.2 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e0.146 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eSocial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e35.3 (11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e36.4 (13.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e35.2 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e0.229 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eSchool\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e34.6 (7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e34.4 (8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e37.9 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e-0.949 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eTotal competence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e27.9 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e28.3 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e28.7 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e-0.054 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eAnxious/depressed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e63.5 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e63.2 (8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e61.3 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e0.518 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eWithdrawn/depressed \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e62.2 (10.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e63.5 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e61.3 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e0.640 (9.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eSomatic complaints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e59.3 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e59 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e59 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e-0.007 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eSocial problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e65.6 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e66.7 (8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e61 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e1.544 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eThought problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e67.9 (12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e67.2 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e73.3 (9.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e-1.055 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eAttention problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e71.3 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e71.7 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e70.2 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e0.392 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eRule-breaking behavior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e65.7 (9.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e63.9 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e71.7 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e-2.002 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eAggressive behavior \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e71.1 (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e71 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e72.7 (6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e-0.507 (12.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eInternalizing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e63.2 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e63 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e65 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e-0.462 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eExternalizing \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e68.5 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e67.8 (9.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e71.3 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e-1.849 (28.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003eTotal score \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.882352941176471%\"\u003e\n \u003cp\u003e69.1 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.705882352941176%\"\u003e\n \u003cp\u003e68.4 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e71.7 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.61764705882353%\"\u003e\n \u003cp\u003e-2.069 (32.87) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.176470588235293%\"\u003e\n \u003cp\u003e.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eNote\u003c/em\u003e. \u003cem\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/em\u003e: total sample of patients for which data for the CBCL was available, \u003cem\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/em\u003e\u003cem\u003e:\u003c/em\u003e Welch homogeneity correction was applied. * p\u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. Logistic regression model of factors associated with pharmacotherapy discontinuation (vs. continuation). \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.42361111111111%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.444444444444443%\"\u003e\n \u003cp\u003eStandardized estimate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.95138888888889%\"\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003eWald statistic (df)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.42361111111111%\"\u003e\n \u003cp\u003eIntellectual disability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.444444444444443%\"\u003e\n \u003cp\u003e1.267\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.95138888888889%\"\u003e\n \u003cp\u003e22.83 (1.40, 373.24) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e4.81 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.42361111111111%\"\u003e\n \u003cp\u003eRule-breaking behavior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.444444444444443%\"\u003e\n \u003cp\u003e1.600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.95138888888889%\"\u003e\n \u003cp\u003e1.19 (1.02, 1.40) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e4.58 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eNote\u003c/em\u003e. N= 40. * p\u0026lt; 0.05.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"psychopharmacology, medication, drug prescribing, adherence, treatment persistence, interruption","lastPublishedDoi":"10.21203/rs.3.rs-1841430/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1841430/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e The present study analyzed data of children and adolescents with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) who referred to the ADHD reference center Scientific Institute IRCCS E. Medea (Brindisi, Italy) for ADHD pharmacotherapy initiation and monitoring overtime. The main aim of the study was to examine differences between patients according to pharmacological treatment status, i.e., treatment continuation vs discontinuation.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Seventy-seven children and adolescents (mean age at pharmacotherapy initiation= 9.5, standard deviation= 2.6) with ADHD received drugs treatment for ADHD at the reference center between January, 2013 and May, 2022. Demographic and clinical data were obtained from the Italian Registry for ADHD and medical records. Child Behavior Checklist (CBCL) available data were used.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Pharmacological treatment status was examined for patients (n= 63) with at least 12 months of follow-up after the first pharmacological administration for ADHD. After starting pharmacotherapy treatment, 49 (77.8%) patients were still on treatment whereas 14 (22.2%) discontinued it. No between group difference was observed on demographic and clinical data except for quotient of intelligence/intellectual disability and rule-breaking behavior (n= 40). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e The findings of this study highlighted the need of periodical assessment monitoring difficulties with (or reasons for poor) treatment compliance in order to provide individualized care, and were discussed according to recent scientific evidence.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Factors associated with pharmacological treatment in children with Attention-Deficit/Hyperactivity Disorders: retrospective study of a series of 77 cases in a single third-level reference center in Apulia Region","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-25 17:34:55","doi":"10.21203/rs.3.rs-1841430/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2e12312b-854e-4526-90ef-ce67aec3b7c0","owner":[],"postedDate":"July 25th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-11-20T15:07:49+00:00","versionOfRecord":{"articleIdentity":"rs-1841430","link":"https://doi.org/10.1186/s13052-023-01560-2","journal":{"identity":"italian-journal-of-pediatrics","isVorOnly":false,"title":"Italian Journal of Pediatrics"},"publishedOn":"2023-11-14 15:01:39","publishedOnDateReadable":"November 14th, 2023"},"versionCreatedAt":"2022-07-25 17:34:55","video":"","vorDoi":"10.1186/s13052-023-01560-2","vorDoiUrl":"https://doi.org/10.1186/s13052-023-01560-2","workflowStages":[]},"version":"v1","identity":"rs-1841430","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1841430","identity":"rs-1841430","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}