Psychosocial risk factors for suicidality in children and adolescents.

Suicidality in childhood and adolescence is of increasing concern. The aim of this paper was to review the published literature identifying key psychosocial risk factors for suicidality in the paediatric population. A systematic two-step search was carried out following the PRISMA statement guidelines, using the terms 'suicidality, suicide, and self-harm' combined with terms 'infant, child, adolescent' according to the US National Library of Medicine and the National Institutes of Health classification of ages. Forty-four studies were included in the qualitative synthesis. The review identified three main factors that appear to increase the risk of suicidality: psychological factors (depression, anxiety, previous suicide attempt, drug and alcohol use, and other comorbid psychiatric disorders); stressful life events (family problems and peer conflicts); and personality traits (such as neuroticism and impulsivity). The evidence highlights the complexity of suicidality and points towards an interaction of factors contributing to suicidal behaviour. More information is needed to understand the complex relationship between risk factors for suicidality. Prospective studies with adequate sample sizes are needed to investigate these multiple variables of risk concurrently and over time.

Development and psychometric properties of the "Suicidality: Treatment Occurring in Paediatrics (STOP) Risk and Resilience Factors Scales" in adolescents.

Suicidality in the child and adolescent population is a major public health concern. There is, however, a lack of developmentally sensitive valid and reliable instruments that can capture data on risk, and clinical and psychosocial mediators of suicidality in young people. In this study, we aimed to develop and assess the validity of instruments evaluating the psychosocial risk and protective factors for suicidal behaviours in the adolescent population. In Phase 1, based on a systematic literature review of suicidality, focus groups, and expert panel advice, the risk factors and protective factors (resilience factors) were identified and the adolescent, parent, and clinician versions of the STOP-Suicidality Risk Factors Scale (STOP-SRiFS) and the Resilience Factors Scale (STOP-SReFS) were developed. Phase 2 involved instrument validation and comprised of two samples (Sample 1 and 2). Sample 1 consisted of 87 adolescents, their parents/carers, and clinicians from the various participating centres, and Sample 2 consisted of three sub-samples: adolescents (n = 259) who completed STOP-SRiFS and/or the STOP-SReFS scales, parents (n = 213) who completed one or both of the scales, and the clinicians who completed the scales (n = 254). The STOP-SRiFS demonstrated a good construct validity-the Cronbach Alpha for the adolescent (α = 0.864), parent (α = 0.842), and clinician (α = 0.722) versions of the scale. Test-retest reliability, inter-rater reliability, and content validity were good for all three versions of the STOP-SRiFS. The sub-scales generated using Exploratory Factor Analysis (EFA) were the (1) anxiety and depression risk, (2) substance misuse risk, (3) interpersonal risk, (4) chronic risk, and (5) risk due to life events. For the STOP-SRiFS, statistically significant correlations were found between the Columbia-Suicide Severity Rating Scale (C-SSRS) total score and the adolescent, parent, and clinical versions of the STOP-SRiFS sub-scale scores. The STOP-SRiFS showed good psychometric properties. This study demonstrated a good construct validity for the STOP-SReFS-the Cronbach Alpha for the three versions were good (adolescent: α = 0.775; parent: α = 0.808; α = clinician: 0.808). EFA for the adolescent version of the STOP-SReFS, which consists of 9 resilience factors domains, generated two factors (1) interpersonal resilience and (2) cognitive resilience. The STOP-SReFS Cognitive Resilience sub-scale for the adolescent was negatively correlated (r = - 0.275) with the C-SSRS total score, showing that there was lower suicidality in those with greater Cognitive Resilience. The STOP-SReFS Interpersonal resilience sub-scale correlations were all negative, but none of them were significantly different to the C-SSRS total scores for either the adolescent, parent, or clinician versions of the scales. This is not surprising, because the items in this sub-scale capture a much larger time-scale, compared to the C-SSRS rating period. The STOP-SReFS showed good psychometric properties. The STOP-SRiFS and STOP-SReFS are instruments that can be used in future studies about suicidality in children and adolescents.

Development and psychometric properties of the Suicidality: Treatment Occurring in Paediatrics (STOP) Suicidality Assessment Scale (STOP-SAS) in children and adolescents.

BACKGROUND: To create a self-reported, internet-based questionnaire for the assessment of suicide risk in children and adolescents. METHODS: As part of the EU project 'Suicidality: Treatment Occurring in Paediatrics' (STOP project), we developed web-based Patient Reported Outcome Measures (PROMs) for children and adolescents and for proxy reports by parents and clinicians in order to assess suicidality. Based on a literature review, expert panels and focus groups of patients, we developed the items of the STOP Suicidality Assessment Scale (STOP-SAS) in Spanish and English, translated it into four more languages, and optimized it for web-based presentation using the HealthTrackerTM platform. Of the total 19 questions developed for the STOP-SAS, four questions that assess low-level suicidality were identified as screening questions (three of them for use with children, and all four for use with adolescents, parents and clinicians). A total of 395 adolescents, 110 children, 637 parents and 716 clinicians completed the questionnaire using the HealthTrackerTM, allowing us to evaluate the internal consistency and convergent validity of the STOP-SAS with the clinician-rated Columbia Suicide Severity Rating Scale (C-SSRS). Validity was also assessed with the receiver operating characteristic (ROC) area of the STOP-SAS with the C-SSRS. RESULTS: The STOP-SAS comprises 19 items in its adolescent, parent, and clinician versions, and 14 items in its children's version. Good internal consistency was found for adolescents (Cronbach's alpha: 0.965), children (Cronbach's alpha: 0.922), parents (Cronbach's alpha: 0.951) and clinicians (Cronbach's alpha: 0.955) versions. A strong correlation was found between the STOP-SAS and the C-SSRS for adolescents (r:0.670), parents (r:0.548), clinicians (r:0.863) and children (r:0.654). The ROC area was good for clinicians' (0.917), adolescents' (0.834) and parents' (0.756) versions but only fair (0.683) for children's version. CONCLUSIONS: The STOP-SAS is a comprehensive, web-based PROM developed on the HealthTrackerTM platform, and co-designed for use by adolescents, children, parents and clinicians. It allows the evaluation of aspects of suicidality and shows good reliability and validity.

[The new German drug market law AMNOG from a child and adolescent psychiatry perspective]. / Das Arzneimittelmarktneuordnungsgesetz aus kinder- und jugendpsychiatrischer Perspektive.

BACKGROUND: The European Union (EU) regulation 1901/2006 plus the implementation of pediatric investigational plans by the European Medicines Agency (EMA) have contributed to more clinical studies in pediatric psychopharmacology. A new drug market law (AMNOG) has been in force in Germany since 2011 that requires an additional process of assessment of benefits of newly authorized medications by the Federal Joint Committee (Gemeinsamer Bundesausschuss, G­BA), which also holds for medications licensed for pediatric populations. OBJECTIVES: Summary of early assessments of benefits for newly registered compounds in the treatment of psychiatric disorders and critical discussion from the perspective of child and adolescent psychiatry. MATERIAL AND METHODS: Application and critical review of documents and written statements by various institutions and stakeholders related to assessment procedures and respective decisions by the G­BA for these medications. RESULTS AND CONCLUSION: Clearly differing requirements for study designs and outcome parameters characterize the conditions for market authorization and for the assessment of benefits. Further adjustments to the regulations in implementing the AMNOG appear to be essential, integrating agencies involved so far, complimented by expertise from regulatory agencies and medical scientific societies.

[Lisdexamfetamine dimesylate: a Treatment Option for Children and Adolescents with Attention Deficit/Hyperactivity Disorder in Germany and Across Europe]. / Lisdexamfetamindimesilat: Eine Behandlungsoption für Kinder und Jugendliche mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung in Deutschland und Europa.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder - which may persist into adolescence and adulthood. Psychostimulants and atomoxetine (ATX) are frequently prescribed to treat ADHD in Germany. Lisdexamfetamine dimesylate (LDX) is the most recently approved ADHD medication in Germany and other European countries. Data used to support the European registration of LDX is summarised from three phase-3/3b studies in children and adolescents with ADHD. Short-term efficacy (study SPD489 - 325), maintenance of efficacy (study SPD489 - 326) and efficacy in patients who had previously responded inadequately to methylphenidate (MPH) treatment (study SPD489 - 317) were demonstrated. The safety and tolerability profile of LDX in all three European studies was shown to be in line with that of other psychostimulants used to treat patients with ADHD.

High rate of non-eligibility: methodological factors impacting on recruitment for a multicentre, double-blind study of paediatric patients with major depressive disorder.

INTRODUCTION: This report describes difficulties encountered when attempting to recruit children and adolescents with major depression for a recent international double-blind, placebo-controlled trial (www.clinicaltrials.gov Nr. NCT00849901). METHODS: Over a 14-month period, children and adolescents with depressive symptoms were pre-screened for their eligibility for inclusion. RESULTS: 85 patients (age 7-17 years) were considered. Of these, only one was enrolled. The main reasons for non-eligibility were: failure to meet the baseline severity criterion on the primary outcome scale (clinical global impression-severity; 32.1% of the patients); requirement for immediate hospitalisation (15.4%); or the presence of an exclusionary comorbid psychiatric disorder (19.1%). DISCUSSION: The recruitment of paediatric patients with major depression was primarily limited by various inclusion and exclusion criteria. Slow recruitment of small patient samples may impact strongly on the representativeness and generalisability of research findings, and thus on analyses in evidence-based medicine and on the development and recommendations of treatment guidelines. This may impact in turn on the feasibility of the clinical development and registration process of new compounds in paediatric psychopharmacology and beyond.

A randomized, waiting list-controlled 12-week trial of atomoxetine in adults with ADHD.

BACKGROUND: With the increasing recognition of adult attention-deficit/hyperactivity disorder (ADHD) there is an emerging need to investigate medication in this population. METHODS: In this waiting list-controlled trial, 64 ADHD-patients (mean age 35.8 ± 8.7 years) were randomly assigned to a daily dosage of up to 80 mg atomoxetine (Atx) or waiting list for 12-weeks. Primary outcome was the change of the observer-rated DSM-IV total ADHD score on the Conners' Adult ADHD Rating Scales (CAARSO: L DSM-IV total ADHD score) from baseline to endpoint. Other efficacy measures included selfrated CAARS-S:L DSM-IV total ADHD score, CAARS-O/S:L problems with self-concept and emotional lability score, Wender-Reimherr Adult Attention Defi cit Disorder Scale Emotional Dysregulation Score, and General Activities Score on the Quality of Life Enjoyment and Satisfaction Questionnaire. Efficacy measures were analysed in the per-protocol population. RESULTS: Mean change in CAARS:O-L DSM-IV total ADHD score was -13.1 ± 7.7 in the Atx vs. -0.4 ± 4.8 in the control group (p < 0.005). Treatment response ( ≥ 30 % reduction) was 60.1 % in the Atx vs. 0 % in the waiting list group. The other efficacy measures also showed significant improvements. The overall incidence of adverse events (AEs) was 70.4 % in the Atx group, the most frequent included fatigue, irritability, nausea and decreased appetite. In Atx-treated patients 18.5 % discontinued early due to AEs. DISCUSSION: Our results suggest that Atx is an effective treatment in adult ADHD. It reduces ADHD core and associated emotional symptoms and increases self-esteem and quality of life. AEs were consistent with those reported in other studies in adult ADHD.

European guidelines on managing adverse effects of medication for ADHD.

The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks.

Rates and predictors of remission and recovery during 3 years in 392 never-treated patients with schizophrenia.

OBJECTIVE: Few studies have prospectively examined remission and recovery as well as their predictors in schizophrenia simultaneously. Aims of the study were to identify remission and recovery rates as well as their predictors in schizophrenia. METHOD: 392 never-treated patients with schizophrenia were assessed over 3 years. Combined remission and recovery required concurrent achievement of symptomatic and functional remission as well as adequate quality of life for at least 6 and 24 months respectively. Predictors were analysed using stepwise logistic regression models. RESULTS: At 3 years, remission rates for symptoms, functioning and subjective wellbeing were 60.3%, 45.4% and 57.0%; recovery rates were 51.7%, 35.0% and 44.3%. Of those, 28.1% were in combined remission and 17.1% in combined recovery. Predictors mainly included the baseline functional status and early remission within the first 3 months. CONCLUSION: The proportion of patients who met combined remission or recovery criteria is low. Early treatment adaptations in case of early non-remission are mandatory.

Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study.

INTRODUCTION: Methylphenidate is the most frequently used medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in Europe. Following concerns about its safety, the European Commission called for research into the long-term effects of methylphenidate on children and adolescents with ADHD. The Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) research programme was designed to address this call. At the heart of this programme is a 2-year longitudinal naturalistic pharmacovigilance study being conducted in 27 European sites. METHODS AND ANALYSIS: 3 cohorts of children and adolescents (aged 6-17) living in the UK, Germany, Italy and Hungary are being recruited:Group 1 (Medicated ADHD): 800 ADHD medication-naive children and adolescents with a clinical diagnosis of ADHD about to start methylphenidate treatment for the first time.Group 2 (Unmedicated ADHD): 400 children and adolescents with a clinical diagnosis of ADHD who have never been treated with ADHD medication and have no intention of beginning medication.Group 3 (Non-ADHD): 400 children and adolescents without ADHD who are siblings of individuals in either group 1 or 2.All participants will be assessed 5 times during their 2-year follow-up period for growth and development, psychiatric, neurological and cardiovascular health. The primary outcome measure will be the height velocity SD score. ETHICS AND DISSEMINATION: Ethical approval for the study has been granted by the East of Scotland Research Ethics Service. Following this approval, patient information leaflets and consent forms were translated as necessary and submissions made by lead sites in each of the other 3 countries to their own ethics committees. Following ethical approval in each country, local ethical permissions at each site were sought and obtained as needed. The study's website (http://www.adhd-adduce.org/page/view/2/Home) provides information for researchers, participants and the general public. TRIAL REGISTRATION NUMBER: NCT01470261.

Cognitive impairment in depressed outpatients as measured with the Dementia Checklist: a simple method for primary care and in field research.

The Dementia Checklist is a 12-item dementia rating scale for physicians who, for whatever reason, cannot be specifically trained. It addresses symptoms of cognitive decline that can easily be identified, and that are typical for different stages of cognitive impairment. This allows an easy classification of the severity of dementia. In a first study, the dementia checklist was used in 937 geriatric outpatients who were treated by neuropsychiatrists for depression. All items contribute to the accuracy of measurement (Cronbach's alpha = 0.84). Differences in cognitive impairment depending on age (chi 2 = 51.7; p < or = 0.001) and depression (chi 2 = 47.6; p < or = 0.001) indicate external validity of the dementia checklist and 5.7% of the outpatients were rated as demented. The Dementia Checklist provides a very economical and easy-to-use assessment of cognitive decline.

Sexual behavior in adolescent and adult females with congenital adrenal hyperplasia.

As part of a comprehensive interview study, 34 female patients with congenital adrenal hyperplasia (CAH) plus 14 control sisters (ages 11-41 yr.) reported on their psychosexual development and sexual orientation (90 items). Fewer patients than sisters had ever experienced love relationships and sexual activities with male partners (p < 0.05 to 0.001). Twenty percent of the patients and none of the sisters wished for and/or had had homosexual relationships; in the patients > 21 yr 44% expressed this interest (p < 0.07). For most items, patients with the salt-wasting variant of CAH (SW) differed more clearly from the sisters than the simple-virilizing patients (SV). For two scales "indicating" homosexual (HOM) and heterosexual orientation (HET) and for two indices of HOM/HET differences), the patients also revealed relatively stronger homosexual and/or weaker heterosexual interests than the sisters (p < 0.05 to 0.001). Here, too, the SW/sister differences were more clear-cut. These results corroborate earlier reports on both delays in reaching psychosexual milestones and increased rates of bisexual/homosexual fantasies and experiences in CAH women.

Congenital adrenal hyperplasia. I: Gender-related behavior and attitudes in female patients and sisters.

Thirty-five female patients with congenital adrenal hyperplasia (CAH) were compared to a group of 16 healthy sisters in regard to gender-related behavioral patterns, present attitudes, and plans for the future. A semi-structured interview with the subjects, ages 11 to 41 yr, and their mothers concentrated on four to five age stages. Results of retrospective data from single items as well as from several related composite scales ("interests and behavior," "appearance," "overall scores") revealed significant group differences: Both in mother-assessment and self-assessment, CAH patients showed a "more masculine" orientation than their sisters, but this was far from consistent across all age stages, especially for single items. Unexpectedly, the gender-behavior differences between CAH patients and sisters did not hold for certain items and scales of "social behavior" (e.g., assertiveness, dominance, acceptance in peer groups) and, in contrast to some of the existing literature, also not for "high-energy expenditure." With regard to expectations for the future, CAH patients had less of a "wish to have their own children" and a higher preference for "having a career versus staying at home." Age, socioeconomic status, intelligence, and presence or absence of a sister as possibly intervening psychosocial/demographic factors could not explain the group differences in behavior. Degree of genital masculinization (Prader stages) or "onset and quality" of therapy as measures of pre- and postnatal androgenization, respectively, could also not account for the degree of the "more masculine" orientation in the CAH group. Nevertheless, the overall results are compatible with earlier findings on the masculinizing effects of prenatal androgens on behavior in humans and point to a time period after sexual differentiation of the genitalia and before birth as the most likely one for the effects of prenatal hormones on behavioral masculinization in humans.

Congenital adrenal hyperplasia. II: Gender-related behavior and attitudes in female salt-wasting and simple-virilizing patients.

The salt-wasting (SW) and simple-virilizing (SV) forms of congenital adrenal hyperplasia (CAH) are characterized by distinct prenatal hormonal milieus. To test whether these hormonal milieus differentially influence the development of a "more masculine" behavioral pattern in female CAH patients (Dittmann et al., 1990), SW patients (N = 13) were compared both to SV patients (N = 20) and healthy sisters of both groups (N = 16). The data are based on semi-structured interviews in which subjects (11-41 yr) and mothers were asked about aspects of "Gender-related interests and behavior," "Level of activity," "Social behavior," (reflecting e.g., assertiveness, dominance, and acceptance by peer groups) and "Appearance"; these areas of interest were represented by composite scales. On most scales, and by both mother-assessment and self-assessment, SW patients differed significantly from both SV patients and sisters in having a "more masculine" orientation. SW patients also showed a higher "Level of activity." These SW group results probably account for much of the CAH/sister differences reported in the companion article (Dittmann et al., 1990). In contrast, SV patients differed from the sister sample on only a few scales. There were no significant differences between SV and SW subjects in the degree of virilization of the external genitalia (indicating no group difference in prenatal androgenization). SW patients were treated "earlier" and "better" after birth (indicating less postnatal androgenization). However, these medical conditions, as well as several psychosocial/demographic variables, could not explain the group behavioral differences. These results do not support a primarily psychosocial explanation of behavioral development in CAH patients, especially those with the SW condition; they rather suggest differential organizational effects of two different hormonal environments (SV vs. SW) during critical periods of prenatal CNS development.

Efficacy and safety findings from naturalistic fluoxetine drug treatment in adolescent and young adult patients.

This article reports on the efficacy and safety of the selective serotonin reuptake inhibitor, fluoxetine, in 213 patients (ages 11-23 years) treated by psychiatrists/neurologists (PN) or general practitioners/internists (GPI). Data were derived from naturalistic drug utilization observation (DUO) studies with fluoxetine (n = 18,759 patients). Data collection--at the start and the end of the observation period (< or =6 weeks)--included patient characteristics, diagnoses, medication, co-medication, efficacy, and adverse events (AEs). Nonparametric statistics and descriptive p values (two-tailed) were used. Analyses revealed various differences between PN (n = 56) and GPI (n = 157) samples as to patient and treatment characteristics (p < 0.001-0.08). Based on both Clinical Global Impression (CGI; all p < 0.001) and self-assessment (total n = 47; Zung SDS, all p < or = 0.003), both PN and GPI patients showed improvements in their symptomatology over time, including suicidality (all p < 0.001; there were no group differences). Overall AE rates were higher in PN patients (p < 0.01; 17.9% vs. 4.5%); the frequency and type of AEs in both subgroups were typical for fluoxetine and the total DUO samples. In fact, AE rates were lower compared to controlled trials. Findings suggest that PN patients were more severely ill at observation start and suffered a more complicated treatment course. However, clinical efficacy showed highly significant improvements in both subgroups; AE rates were low in both--although higher in PN patients. Thus, results support a positive benefit/risk ratio of fluoxetine use for this young patient population.

Slow progression of juvenile metachromatic leukodystrophy 6 years after bone marrow transplantation.

Metachromatic leukodystrophy refers to a group of genetic neurologic diseases caused by deficiencies of the enzyme arylsulfatase A and the resulting accumulation of sulfatides in white matter. Bone marrow transplantation has been advocated as a treatment in an attempt to correct the enzyme deficiency. Such a transplant was performed in 1991 in a 16-year-old girl with a form of late juvenile metachromatic leukodystrophy caused by a homozygous P426L mutation in the arylsulfatase A gene. Engraftment was prompt and resulted in constant enzymatic normalization of circulating lymphocytes. The elevated urinary excretion of sulfatides remained unaffected. Clinical findings up until transplantation consisted of gait disturbances, impairment of cognitive functioning, and deterioration in school performance over several years. During a 6-year follow-up period, the patient's condition was subject to major fluctuations but, on the whole, findings showed slow neurologic and neurophysiologic deterioration. The clinical course observed after bone marrow transplantation probably more or less reflects the natural course expected in this form of late-onset metachromatic leukodystrophy.

Driving performance in adults with ADHD: results from a randomized, waiting list controlled trial with atomoxetine.

PURPOSE: To investigate effects of a 12-week treatment with atomoxetine (ATX) on driving performance in real traffic, driving-related neuropsychological performance tests and self-evaluation of driving in adult patients with ADHD compared to an untreated control group with ADHD. METHODS: Parallel group design with an ATX and a waiting list group. At baseline and endpoint patients were evaluated with a standardized on-road driving test (SDBO), a driving-related neuropsychological test battery (Act and React Test System [ART2020]), and subjective measures of driving performance (one-week driving diary, Driver Coping Questionnaire). RESULTS: Forty-three of the 64 included patients completed the study (n=22 ATX, n=21 controls). Mean intervention period was 11.9±3.0 weeks, mean daily ATX dosage was 71.6±14.9mg. At endpoint, 60.1% of patients treated with ATX and 0% of waiting list group had reduced ADHD symptoms by greater or equal to 30%. In SDBO, ATX group reduced driving errors in three of four driving performance categories (attention, P<0.05; risk-related self-control, P<0.005; driver skills, P<0.001), number of driving errors remained stable in control group. At endpoint, 47.6% of control group and 18.2% of ATX group (P<0.05) did not fulfil the driving fitness criteria according to German Guidelines (percentile rank less or equal to 16 in one or more subtests in ART2020). Total number of self-reported critical traffic situations decreased from 12.0 to 6.8 per week in ATX group (P<0.05) and remained stable in controls by 9.3 and 9.9 at baseline and endpoint (ns). Coping strategies with stressful traffic situations did not change within both groups. CONCLUSION: Our study provides first evidence that treatment with ATX improves driving performance in real traffic in adults with ADHD.

[The effectiveness of atomoxetine in children, adolescents, and adults with ADHD. A systematic overview]. / Wirksamkeit von Atomoxetin bei Kindern, Jugendlichen und Erwachsenen mit ADHS. Eine systematische Ubersicht.

This paper gives an overview of the pharmacology, efficacy, duration, tolerance, and side effects of atomoxetine for children, adolescents, and adults. A systematic analysis of the published clinical studies and poster abstracts was conducted. Atomoxetine is the first selective inhibitor of the noradrenaline transporter that was approved by the FDA in the US as a nonstimulant for the treatment of ADHD in children, adolescents, and adults. In clinical studies, its efficacy was studied in 4,000 patients. Compared with placebo, atomoxetine proved to be superior with respect to reducing impulsiveness, hyperactivity, and inattention. There are indications that its efficacy is comparable to that of methylphenidate. In general, atomoxetine was well tolerated. The most frequently reported adverse events were decrease of appetite, abdominal problems, tiredness, and vertigo. These were classified as mild and found mostly at the beginning of treatment. The existing results indicate that atomoxetine is promising for the treatment of ADHD in children, adolescents, and adults.