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Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. It is the most common neurodevelopmental disorder presenting to pediatric services, and pediatricians are often involved in the early assessment, diagnosis, and treatment of children with ADHD. The treatment of ADHD typically involves a multimodal approach that encompasses a combination of psychoeducation, parent/teacher training, psychosocial/psychotherapeutic interventions, and pharmacotherapy. Concerning pharmacotherapy, guidelines vary in drug choice and sequencing, with psychostimulants, such as methylphenidate and (lis)dexamfetamine, generally being the favored initial treatment. Alternatives include atomoxetine and guanfacine. Pharmacotherapy has been proven effective, but close follow-up focusing on physical growth, cardiovascular monitoring, and the surveillance of potential side effects including tics, mood fluctuations, and psychotic symptoms, is essential. This paper presents an overview of current pharmacological treatment options for ADHD and explores disparities in treatment guidelines across different European countries.   Conclusion: Pharmacological treatment options for ADHD in children and adolescents are effective and generally well-tolerated. Pharmacotherapy for ADHD is always part of a multimodal approach. While there is a considerable consensus among European guidelines on pharmacotherapy for ADHD, notable differences exist, particularly concerning the selection and sequencing of various medications. What is Known: • There is a significant base of evidence for pharmacological treatment for ADHD in children and adolescents. • Pediatricians are often involved in assessment, diagnosis and management of children with ADHD. What is New: • Our overview of different European guidelines reveals significant agreement in the context of pharmacotherapy for ADHD in children and adolescents. • Discrepancies exist primarily in terms of selection and sequencing of different medications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age., Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age., Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable., Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SC reports collaboration on projects from the EU Seventh Framework Program and on clinical trials sponsored by Lundbeck, Otsuka, Janssen-Cilag, Angelini and Acadia. KKCM reports grants from the CW Maplethorpe Fellowship, the UK National Institute for Health and Care Research (NIHR), the EU Horizon 2020 Framework, and the Hong Kong Research Grant Council, and personal fees from IQVIA Holdings, outside the submitted work. CB reports collaboration on projects from the EU Seventh Framework Program and on clinical trials sponsored by Otsuka, Janssen-Cilag, Angelini and Acadia. JB has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda, Medice, Angelini, Janssen, Boehringer-Ingelheim, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. MD has received research funding from Takeda–Shire, outside the submitted work. RWD—For the past 3 years, he has no conflicts of interest to report. As a former company employee, he has been a stockholder of Eli Lilly & Co. FD reports collaboration as sub-investigator in clinical trials sponsored by Lundbeck as an independent rater in clinical trials sponsored by Servier and Acadia. BF has been a consultant or speaker for Abbvie, Actelion, Allergan, Almirall, Alnylam, Amgen, Astellas, Astrazeneca, Bayer, Biogen, Biopecs, Bioproject, Biotronik, BMS,Boehringer, Celgène, Daiichi-Sankyio, Ethypharm, Forestlab, Genevrier, Genzyme, Gilead, Grünenthal, GSK, Idorsia, IMS, Indivior, IQVIA, JNJ, Léo, Lilly, Lundbeck, Menarini, MSD, Novartis, Novonordisk, Otsuka, Pfizer, Pierre-Frabre, Recordati, Roche, SANOFI, Servier, Takeda, UCB, ViiV, and Wellmera. AH has received compensation for serving as consultant or speaker for Shire–Takeda and Medice, unrelated to this work. KKCM reports grants from the CW Maplethorpe Fellowship, the UK National Institute for Health and Care Research (NIHR), the EU Horizon 2020 Framework, and the Hong Kong Research Grant Council, and personal fees from IQVIA Holdings, outside the submitted work. CH reports research funding from the NIHR including the Health Technology Assessment SATURN trial (grant ref: NIHR128472) comparing methylpheidate with guanfacine for children and young people with ADHD and tics. CH was chair of the NICE Guideline (CG155) for psychosis and schizophrenia in children and young people; member of the NICE ADHD Guideline Update committee (NG87) and is a member of Eunethydis and the Europhean ADHD Guideline Group. SM reports speaker’s fee, travel support, and research support from Shire, outside the submitted work. AN reports research funding from the EU, the German Ministry of Health, and the German Federal Joint Committee, outside the submitted work. PN has been a consultant or speaker for Medice, Servier, and Egis Pharmaceuticals, outside the submitted work. ER received speaker’s fee and travel support from Shire, outside the submitted work. PN has been a consultant or speaker for Medice, Servier, and Egis Pharmaceuticals, outside the submitted work. ER received speaker’s fee and travel support from Shire, outside the submitted work. ESB has received in the last 3 years speakers fees from Takeda and Medice and research support from QBTech. AZ served in an advisory or consultancy role for Angelini, EduPharma, Servier; received conference support or speaker’s fee from Angelini and Janssen; participated in clinical trials conducted by Angelini, Janssen, Lundbeck, Otsuka, Roche, Sevier, and Shire; and received royalties from Giunti OS and Oxford University Press. ICKW reports research and educational funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, Takeda, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, the Hong Kong Innovation and Technology Commission, the NIHR, the EU, and the Australian National Health and Medical Research Council, and the expert testimony payment from the Hong Kong Court of Final Appeal; outside the submitted work. TB served in an advisory or consultancy role for eye level, Infectopharm, Medice, Neurim Pharmaceuticals, Oberberg GmbH and Takeda. He received conference support or speaker’s fee by Janssen, Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. DC reports, in the past 3 years, a consultant, member of advisory board, or speaker role for Takeda–Shire, Medice, Novartis, and Servier. He has received royalties from Oxford University Press and Cambridge University Press; research support from the Australian National Health and Medical Research Council and the Royal Children’s Hospital Foundation; and funding for the current study from the European Commission. All other authors declare no competing interests.

Objective: Short-term RCTs have demonstrated that MPH-treatment significantly reduces ADHD-symptoms, but is also associated with adverse events, including sleep problems. However, data on long-term effects of MPH on sleep remain limited., Methods: We performed a 2-year naturalistic prospective pharmacovigilance multicentre study. Participants were recruited into three groups: ADHD patients intending to start MPH-treatment (MPH-group), those not intending to use ADHD-medication (no-MPH-group), and a non-ADHD control-group. Sleep problems were assessed with the Children's-Sleep-Habits-Questionnaire (CSHQ)., Results: 1,410 participants were enrolled. Baseline mean CSHQ-total-sleep-scores could be considered clinically significant for the MPH-group and the no-MPH-group, but not for controls. The only group to show a significant increase in any aspect of sleep from baseline to 24-months was the control-group. Comparing the MPH- to the no-MPH-group no differences in total-sleep-score changes were found., Conclusion: Our findings support that sleep-problems are common in ADHD, but don't suggest significant negative long-term effects of MPH on sleep., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AH has received compensation for serving as consultant or speaker for Shire–Takeda and Medice, unrelated to this work. KKCM reports grants from the CW Maplethorpe Fellowship, the UK National Institute for Health and Care Research (NIHR), the EU Horizon 2020 Framework, and the Hong Kong Research Grant Council, and personal fees from IQVIA Holdings, outside the submitted work. JB has been in the past 3 years a consultant, member of advisory board, or speaker for Takeda–Shire, Roche, Medice, Angelini, Janssen, and Servier. SC reports collaboration on projects from the EU Seventh Framework Programme and on clinical trials sponsored by Shire Pharmaceutical Company, Lundbeck, Otsuka, Janssen-Cilag, and Angelini. MD has received research funding from Takeda–Shire, outside the submitted work. RWD—For the past 3 years, he has no conflicts of interest to report. As a former company employee, he has been a stock holder of Eli Lilly & Co. BF has been a consultant or speaker for Abbvie, Actelion, Allergan, Almirall, Alnylam, Amgen, Astellas, Astrazeneca, Bayer, Biogen, Biopecs, Bioproject, Biotronik, BMS, Boehringer, Celgène, Daiichi-Sankyio, Ethypharm, Forestlab, Genevrier, Genzyme, Gilead, Grünenthal, GSK, Idorsia, IMS, Indivior, IQVIA, JNJ, Léo, Lilly, Lundbeck, Menarini, MSD, Novartis, Novonordisk, Otsuka, Pfizer, Pierre-Frabre, Recordati, Roche, SANOFI, Servier, Takeda, UCB, ViiV, and Wellmera. CH reports research funding from the NIHR including the Health Technology Assessment SATURN trial (grant ref: NIHR128472) comparing MPH with guanfacine for children and young people with ADHD and tics. CH was chair of the NICE Guideline (CG155) for psychosis and schizophrenia in children and young people; member of the NICE ADHD Guideline Update committee (NG87) and is a member of Eunethydis and the European ADHD Guideline Group. SM reports speaker’s fee, travel support, and research support from Shire, outside the submitted work. AN reports research funding from the EU, the German Ministry of Health, and the German Federal Joint Committee, outside the submitted work. PN has been a consultant or speaker for Medice, Servier, and Egis Pharmaceuticals, outside the submitted work. ER received speaker’s fee and travel support from Shire, outside the submitted work. ESB has received in the last 3 years speakers fees from Takeda and Medice and research support from QBTech. AZ served in an advisory or consultancy role for Angelini, EduPharma, Servier; received conference support or speaker’s fee from Angelini and Janssen; participated in clinical trials conducted by Angelini, Janssen, Lundbeck, Otsuka, Roche, Servier, and Shire; and received royalties from Giunti OS and Oxford University Press. ICKW reports research and educational funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, Takeda, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, the Hong Kong Innovation and Technology Commission, the NIHR, the EU, and the Australian National Health and Medical Research Council, and the expert testimony payment from the Hong Kong Court of Final Appeal; outside the submitted work. DC reports, in the past 3 years, a consultant, member of advisory board, or speaker role for Takeda–Shire, Medice, Novartis, and Servier. He has received royalties from Oxford University Press and Cambridge University Press; research support from the Australian National Health and Medical Research Council and the Royal Children’s Hospital Foundation; and funding for the current study from the European Commission. All other authors declare no competing interests. TB served in an advisory or consultancy role for Eyelevel, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg, Roche, and Takeda; received conference support or speaker’s fee from Jansen, Medice, and Takeda; and royalities from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press; outside the submitted work.

Background: Methylphenidate is the most frequently prescribed medication for the treatment of ADHD in children and adolescents in many countries. Although many randomised controlled trials support short-term efficacy, tolerability, and safety, data on long-term safety and tolerability are scarce. The aim of this study was to investigate the safety of methylphenidate over a 2-year period in relation to growth and development, psychiatric health, neurological health, and cardiovascular function in children and adolescents., Methods: We conducted a naturalistic, longitudinal, controlled study as part of the ADDUCE research programme in 27 European child and adolescent mental health centres in the UK, Germany, Switzerland, Italy, and Hungary. Participants aged 6-17 years were recruited into three cohorts: medication-naive ADHD patients who intended to start methylphenidate treatment (methylphenidate group), medication-naive ADHD patients who did not intend to start any ADHD medication (no-methylphenidate group), and a control group without ADHD. Children with ADHD diagnosed by a qualified clinician according to the DSM-IV criteria and, in the control group, children who scored less than 1·5 on average on the Swanson, Nolan, and Pelham IV rating scale for ADHD items, and whose hyperactivity score on the parent-rated Strengths and Difficulties Questionnaire was within the normal range (<6) were eligible for inclusion. Participants were excluded if they had previously taken any ADHD medications but remained eligible if they had previously taken or were currently taking other psychotropic drugs. The primary outcome was height velocity (height velocity SD score; estimated from at least two consecutive height measurements, and normalised with reference to the mean and SD of a population of the same age and sex)., Findings: Between Feb 01, 2012, and Jan 31, 2016, 1410 participants were enrolled (756 in methylphenidate group, 391 in no-methylphenidate group, and 263 in control group). 1070 (76·3%) participants were male, 332 (23·7%) were female, and for eight gender was unknown. The average age for the cohort was 9·28 years (SD 2·78; IQR 7-11). 1312 (93·0%) of 1410 participants were White. The methylphenidate and no-methylphenidate groups differed in ADHD symptom severity and other characteristics. After controlling for the effects of these variables using propensity scores, there was little evidence of an effect on growth (24 months height velocity SD score difference -0·07 (95% CI -0·18 to 0·04; p=0·20) or increased risk of psychiatric or neurological adverse events in the methylphenidate group compared with the no-methylphenidate group. Pulse rate and systolic and diastolic blood pressure were higher in the methylphenidate group compared with the no-methylphenidate group after 24 months of treatment. No serious adverse events were reported during the study., Interpretation: Our results suggest that long-term treatment with methylphenidate for 2 years is safe. There was no evidence to support the hypothesis that methylphenidate treatment leads to reductions in growth. Methylphenidate-related pulse and blood pressure changes, although relatively small, require regular monitoring., Funding: EU Seventh Framework Programme., Competing Interests: Declaration of interests KKCM reports grants from the CW Maplethorpe Fellowship, the UK National Institute for Health and Care Research (NIHR), the EU Horizon 2020 Framework, and the Hong Kong Research Grant Council, and personal fees from IQVIA Holdings, outside the submitted work. AH has received compensation for serving as consultant or speaker for Shire–Takeda and Medice, unrelated to this work. TB served in an advisory or consultancy role for Eyelevel, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg, Roche, and Takeda; received conference support or speaker's fee from Jansen, Medice, and Takeda; and royalities from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press; outside the submitted work. JB has been in the past 3 years a consultant, member of advisory board, or speaker for Takeda–Shire, Roche, Medice, Angelini, Janssen, and Servier. SC reports collaboration on projects from the EU Seventh Framework Programme and on clinical trials sponsored by Shire Pharmaceutical Company, Lundbeck, Otsuka, Janssen-Cilag, and Angelini. MD has received research funding from Takeda–Shire, outside the submitted work. RWD has received compensation for serving as consultant or speaker, or he or the institution he works for have received research support or royalties from: EU Seventh Framework Programme, US National Institute of Mental Health (NIMH), German Federal Ministry of Health–Regulatory Agency, German Federal Ministry of Education and Research, German Research Foundation, Volkswagen Foundation; Boehringer Ingelheim, Ferring, Janssen-Cilag, Lilly, Lundbeck, Otsuka, Servier, Shire, Sunovion–Takeda, and Theravance. He was a former employee in clinical CNS research of Eli Lilly until Aug 2008, and owns Eli Lilly stock (small part of the respective annual salary). BF has been a consultant or speaker for Abbvie, Actelion, Allergan, Almirall, Alnylam, Amgen, Astellas, Astrazeneca, Bayer, Biogen, Biopecs, Bioproject, Biotronik, BMS, Boehringer, Celgène, Daiichi-Sankyio, Ethypharm, Forestlab, Genevrier, Genzyme, Gilead, Grünenthal, GSK, Idorsia, IMS, Indivior, IQVIA, JNJ, Léo, Lilly, Lundbeck, Menarini, MSD, Novartis, Novonordisk, Otsuka, Pfizer, Pierre-Frabre, Recordati, Roche, SANOFI, Servier, Takeda, UCB, ViiV, and Wellmera. CH reports research funding from the NIHR including the Health Technology Assessment SATURN trial (grant ref: NIHR128472) comparing methylpheidate with guanfacine for children and young people with ADHD and tics. CH was chair of the NICE Guideline (CG155) for psychosis and schizophrenia in children and young people; member of the NICE ADHD Guideline Update committee (NG87) and is a member of Eunethydis and the Europhean ADHD Guideline Group. SM reports speaker's fee, travel support, and research support from Shire, outside the submitted work. AN reports research funding from the EU, the German Ministry of Health, and the German Federal Joint Committee, outside the submitted work. PN has been a consultant or speaker for Medice, Servier, and Egis Pharmaceuticals, outside the submitted work. ER received speaker's fee and travel support from Shire, outside the submitted work. ESB has received in the last 3 years speakers fees from Takeda and Medice and research support from QBTech. AZ served in an advisory or consultancy role for Angelini, EduPharma, Servier; received conference support or speaker's fee from Angelini and Janssen; participated in clinical trials conducted by Angelini, Janssen, Lundbeck, Otsuka, Roche, Sevier, and Shire; and received royalties from Giunti OS and Oxford University Press. ICKW reports research and educational funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, Takeda, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, the Hong Kong Innovation and Technology Commission, the NIHR, the EU, and the Australian National Health and Medical Research Council, and the expert testimony payment from the Hong Kong Court of Final Appeal; outside the submitted work. DC reports, in the past 3 years, a consultant, member of advisory board, or speaker role for Takeda–Shire, Medice, Novartis, and Servier. He has received royalties from Oxford University Press and Cambridge University Press; research support from the Australian National Health and Medical Research Council and the Royal Children's Hospital Foundation; and funding for the current study from the European Commission. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Although instrumental learning deficits are, among other deficits, assumed to contribute to attention-deficit/hyperactivity disorder (ADHD), no comprehensive systematic review of instrumental learning deficits in ADHD exists. This review examines differences between ADHD and typically developing (TD) children in basic instrumental learning and the effects of reinforcement form, magnitude, schedule, and complexity, as well as effects of medication, on instrumental learning in children with ADHD., Method: A systematic search of PubMed, PsyINFO, CINAHL, EMBASE+EMBASE CLASSIC, ERIC, and Web of Science was conducted for articles up to March 16, 2020. Experimental studies comparing instrumental learning between groups (ADHD versus TD) or a manipulation of reinforcement/medication within an ADHD sample were included. Quality of studies was assessed with an adapted version of the Hombrados and Waddington criteria to assess risk of bias in (quasi-) experimental studies., Results: A total of 19 studies from among 3,384 non-duplicate screened articles were included. No difference in basic instrumental learning was found between children with ADHD and TD children, nor effects of form or magnitude of reinforcement. Results regarding reinforcement schedule and reversal learning were mixed, but children with ADHD seemed to show deficits in conditional discrimination learning compared to TD children. Methylphenidate improved instrumental learning in children with ADHD. Quality assessment showed poor quality of studies with respect to sample sizes and outcome and missing data reporting., Conclusion: The review identified very few and highly heterogenous studies, with inconsistent findings. No clear deficit was found in instrumental learning under laboratory conditions. Children with ADHD do show deficits in complex forms of learning, that is, conditional discrimination learning. Clearly more research is needed, using more similar task designs and manipulations., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Methylphenidate (MPH) is an efficacious treatment for ADHD but concerns have been raised about potential adverse effects of extended treatment on growth., Objectives: To systematically review the literature, up to December 2018, conducting a meta-analysis of association of long-term (> six months) MPH exposure with height, weight and timing of puberty., Results: Eighteen studies (ADHD n = 4868) were included in the meta-analysis. MPH was associated with consistent statistically significant pre-post difference for both height (SMD = 0.27, 95% CI 0.16-0.38, p < 0.0001) and weight (SMD = 0.33, 95% CI 0.22-0.44, p < 0.0001) Z scores, with prominent impact on weight during the first 12 months and on height within the first 24-30 months. No significant effects of dose, formulation, age and drug-naïve condition as clinical moderators were found. Data on timing of puberty are currently limited., Conclusions: Long-term treatment with MPH can result in reduction in height and weight. However, effect sizes are small with possible minimal clinical impact. Long-term prospective studies may help to clarify the underlying biological drivers and specific mediators and moderators., (Copyright © 2020. Published by Elsevier Ltd.)

Methylphenidate (MPH), the most common medication for children with Attention Deficit/Hyperactivity Disorder (ADHD) in many countries, is often prescribed for long periods of time. Any long-term psychotropic treatment in childhood raises concerns about possible adverse neurological and psychiatric outcomes. We aimed to map current evidence regarding neurological and psychiatric outcomes, adverse or beneficial, of long-term MPH (> 1 year) treatment in ADHD. We coded studies using a "traffic light" system: Green: safe/favours MPH; Amber: warrants caution; Red: not safe/not well-tolerated. Un-categorisable study findings were coded as "Unclear". Although some evidence suggests an elevated risk of psychosis and tics, case reports describe remission on discontinuation. Several studies suggest that long-term MPH may reduce depression and suicide in ADHD. Evidence suggests caution in specific groups including pre-school children, those with tics, and adolescents at risk for substance misuse. We identified a need for more studies that make use of large longitudinal databases, focus on specific neuropsychiatric outcomes, and compare outcomes from long-term MPH treatment with outcomes following shorter or no pharmacological intervention., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Concerns have been raised over the safety of methylphenidate (MPH), with regard to adverse effects on growth and blood pressure. Our study investigates whether, and to what extent, methylphenidate use in boys with ADHD is associated with having low body mass index (BMI), having low height, and increased systolic and diastolic blood pressure., Methods: Data used for this study stem from the German KiGGS dataset. Three different groups of boys aged 6-15 years were included in the analysis: ADHD patients who used MPH for less than 12 months; ADHD patients who used MPH for 12 months or more; and ADHD patients without current MPH treatment. Each of these three groups was compared to a non-ADHD control group regarding low weight (BMI ≤ 3rd percentile), low height (≤3rd percentile) and raised systolic and diastolic blood pressure. For growth outcomes, boys were categorized according to age (< 11 years/≥11 years, to account for pubertal maturation). Multivariable logistic regression was conducted to test for associations., Results: 4244 boys were included in the study; MPH < 12 months: n = 65 (n = 36 < 11 years), MPH ≥ 12 months: n = 53 (n = 22 < 11 years), ADHD controls: n = 320 (n = 132 < 11 years), non-ADHD controls: n = 3806 (n = 2003 < 11 years). Pre-pubertal boys with MPH use less than 12 months and pubertal/postpubertal boys with MPH use of 12 months or greater were significantly more likely to have a BMI ≤ 3rd percentile compared to non-ADHD controls. Boys from the ADHD control group were significantly less likely to have a raised systolic blood pressure compared to non-ADHD controls. Beyond that, no significant between group differences were observed for any other growth and BP parameter., Conclusion: The analyses of the KiGGS dataset showed that MPH use in boys with ADHD is associated with low BMI. However, this effect was only observed in certain groups. Furthermore, our analysis was unable to confirm that MPH use is also associated with low height (≤3rd percentile) and changes in blood pressure.

Objective: There is no questionnaire to specifically monitor perceived adverse events of methylphenidate (MPH) on cognition, motivation, and mood. The current study therefore had two goals. First, to harvest accounts of such putative events from transcripts of interviews in samples enriched for such potential experiences. Second, to use the derived data to generate items for a new questionnaire that can be used for monitoring such events in medication trials or routine clinical care., Methods: Following a literature search aimed at identifying associations between MPH and cognition and/or motivation, a qualitative semistructured interview was designed to focus specifically on the domains of cognition (i.e., reasoning, depth/breadth of thinking, intellectual capacity, and creativity) and motivation (i.e., drive, effort, and attitudes toward rewards/incentives). Interviews were conducted with 45 participants drawn from the following four groups: (a) clinicians, child and adolescent psychiatrists, and pediatricians specializing in attention-deficit/hyperactivity disorder (ADHD) (n = 15); (2) teachers, with experience of teaching at least 10 medicated children with ADHD (n = 10); (3) parents of children with ADHD (n = 8) treated with MPH; and (4) adolescents/adults with ADHD (n = 12). Purposeful sampling was used to selectively recruit ADHD participants whose histories suggested a degree of vulnerability to MPH adverse events. Data were analyzed using a deductive approach to content analysis., Results: While we probed purposefully for cognitive and motivational adverse events, a third domain, related to mood, emerged from the reports. Therefore, three domains, each with a number of subdomains, were identified from the interview accounts: (i) Cognition (six subdomains; attention/concentration, changes in thinking, reduced creativity, sensory overload, memory, slower processing speed); (ii) motivation (four subdomains; loss of intrinsic motivation for goal-directed activities, external locus of control, lack of effort/engagement in daily tasks, increased focus on incentives); and (iii) mood (three subdomains; dampening of spontaneity/flat affect, mood dysregulation, increased anxiety/edginess). On the basis of these reports, 34 items were specified and incorporated into a prototype questionnaire, which was piloted and refined on the basis of field-testing., Conclusions: Items were identified that capture potential/perceived cognitive, motivational, and mood-related adverse events of MPH. The items generated will allow us to further develop and psychometrically examine their prevalence, and the extent to which they are associated with medication adherence, treatment outcome, impairment, and other reported adverse events (e.g., loss of appetite/cardiovascular effects).

Psychopharmacological agents were shown to be important for improving the quality of life (QoL) of patients with attention-deficit/hyperactivity disorder (ADHD). A short-term, 10-week study found atomoxetine (ATX) to be effective in improving QoL of ADHD patients. We compared, for the first time, long-term treatment outcomes of ATX and other early standard therapy (OEST, any pharmacological ADHD treatment except ATX) in QoL and functional impairment in pharmacologically naive children/ adolescents in a randomized, controlled, open-label study at 6 and 12 months. Patients received ATX (0.5-1.8 mg/kg per day) or OEST (mainly methylphenidate). Quality of life and functioning were assessed by the Child Health and Illness Profile-Child Edition, Parent Rating Form and the Weiss Functional Impairment Rating Scale-Parent Report. Three hundred ninety-eight patients (79.4% male; mean age, 9.3 years) received study treatment. The Child Health and Illness Profile-Child Edition, Parent Rating Form achievement domain t scores significantly improved from baseline to 6 months from means of 28.0 to 37.1 for ATX and from 28.3 to 40.7 for OEST. Mean t scores at 12 months were 40.0 for ATX and 41.0 for OEST. The Weiss Functional Impairment Rating Scale-Parent Report total score improved from baseline to 6 months in both groups (ATX: mean 1.02 to 0.63; OEST: 0.96 to 0.59). Both treatments were safe with no statistically significant difference in the overall rate of adverse events. Overall, the improvements in QoL and functional impairment observed over time for ATX and OEST were meaningful and stable over the study period of 12 months. Between-group differences were small but sometimes statistically significant, providing the first-time long-term comparative symptomatic and QoL analysis between ATX and OEST.

Despite evidence for its efficacy and effectiveness, the use of medication for the treatment of ADHD remains controversial. Little is known about the factors that influence clinicians' decisions to use medication for ADHD. Here, we present initial data on the attitudes of prescribing clinicians from the Influences on Prescribing for ADHD Questionnaire (IPAQ)-a new clinician-completed, 40-item scale. The eight IPAQ subscales cover attitudes towards (1) treatment outcome optimisation, (2) the use of rule based over more informal approaches, (3) side effects, (4) symptoms control as the primary goal of treatment, (5) the influence of external pressure on medication-related decisions, (6) the value of taking the child's views into account, (7) long-term medication use and (8) the value of psychosocial approaches for the treatment of ADHD. Sixty-eight clinicians from Belgium and the UK took part. All subscales had acceptable levels of internal reliability (Chronbach's alpha = 0.62-0.78). Overall, clinicians reported taking a rule-based approach to prescribing with a focus on treatment optimisation, taking the child's view into account and valuing psycho-social approaches. They focused on treating broader patterns of impairment, but were wary of the potential side effects and long-term treatment. Psychiatrists scored high on their focus on symptom control and preference for long-term medication use, while paediatricians reported using more rule-based approaches. We identified four distinctive response profiles: (1) pro-psychosocial; (2) medication focused; (3) unsystematic; and (4) response optimizers. Future larger scale studies are required to replicate these profiles and to explore their relationship with prescribing behaviour and treatment outcomes.