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Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders Abstract: As a vulnerable group, minors require special protection in studies. For this reason, researchers are often reluctant to initiate studies, and ethics committees are reluctant to authorize such studies. This often excludes minors from participating in clinical studies. This exclusion can lead to researchers and clinicians receiving only incomplete data or having to rely on adult-based findings in the treatment of minors. Using the example of the study "Computer-Assisted Risk Evaluation in the Early Detection of Psychotic Disorders" (CARE), which was conducted as an 'other clinical investigation' according to the Medical Device Regulation, we present a line of argumentation for the inclusion of minors which weighs the ethical principles of nonmaleficence (especially regarding possible stigmatization), beneficence, autonomy, and fairness. We show the necessity of including minors based on the development-specific differences in diagnostics and early intervention. Further, we present specific protective measures. This argumentation can also be transferred to other disorders with the onset in childhood and adolescence and thus help to avoid excluding minors from appropriate evidence-based care because of insufficient studies.

Experiences of Violence During Inpatient Child and Adolescent Psychiatric Treatment: An Explorative Study with Implications for Child Protection Abstract. Objective: Educational and medical institutions care for children and adolescents by providing supervision, schooling, education, therapy, and protection. Nevertheless, children in institutional care are exposed to potential danger through maltreatment and abuse. Method: As part of the establishment of the protection concept at the University Hospital for Child and Adolescent Psychiatry in Würzburg, a retrospective patient survey was conducted. The study population consisted of former inpatient clients from 2006 and 2007, who at the time of the catamnesis were of legal age. The survey was conducted by mail. In addition to items on their experiences of violence, the questionnaire included established scales to assess treatment satisfaction and quality of life (FBB-K, WHO-BREF). Results: Of 568 former patients, 87 (15.3 %) provided valid responses (59 female, mean age at the time of the survey: 24.5 years): 35 former patients (40.2 % of the participants) reported experiences of violence during their inpatient treatment (26 victims only, 7 experiences as victims and perpetrators, and 2 perpetrators only). Experiences as victims mainly included emotional violence (34.5 %), but also physical (5.7 %) and sexual violence (10.3 %). Conclusion: We found a significant correlation between experiences of violence, on the one hand, and retrospective treatment satisfaction and current quality of life, on the other hand. The results of the survey underline the importance of establishing protection concepts in clinics and other institutions.

The Pharmacological Management of Emergencies in Child and Adolescent Psychiatry Abstract. Emergencies in child and adolescent psychiatry are highly prevalent and often pose significant challenges to physicians, since substantial danger to the patient or others must be avoided through the application of largely moderate interventions. Besides using de-escalating strategies and exploiting psychotherapeutic options, the physician frequently employs psychopharmacological interventions. because of a lack of systematically assessed data, however, in emergencies in child and adolescent psychiatry most administrations of psychotropic drugs occur "off label." This review deduces practice-relevant recommendations for the pharmacological management of occurring child and adolescent emergencies such as acute suicidality, acute psychotic episodes, delirium, disorders of consciousness, acute intoxication, and alcohol withdrawal syndrome. We discuss the issue of quality and safety in pharmacological emergency strategies.

Freedom-restricting measures in Bavarian residential facilities for children, adolescents, and young adults with intellectual disabilities Abstract. Objective: In Bavaria, around 10 % of youths with an intellectual disability (ID) live in residential facilities. In 2015, media raised accusations of inadmissible use of coercive measures. The REDUGIA project carried out a representative survey in Bavarian facilities regarding coercive measures (FeM), challenging behavior (hfV), and employee stress (MaB). Method: We sent a questionnaire concerning structural conditions, MaB, hfV and FeM to 65 Bavarian facilities for young people with ID. In addition to preparing descriptive evaluations, we performed correlative and regression analyses concerning the relationship between hfV, FeM, and MaB. Results: We retrieved data from 1,839 subjects in 61 facilities. 84.3 % of facilities reported low rates of hfV and FeM, while 15.7 % reported an increased incidence of hfV and FeM. For n = 1809 full-time position equivalents there were 639 physical attacks by residents over the course of 14 days. We observed 85 instances of sick leave and 33 transfer apllications/resignation associated with hfV. The frequency of hfV predicted the frequency of FeM ( R ² = 0.307, F = 21.719, p < .001). MaB correlated positively with hfV ( r = 0.507, p < .001). Conclusions: The descriptive data indicate that hfV and FeM are not general phenomena but occur mainly in a circumscript number of highly specialized facilities. This emphasizes the need for prevention of hfV and FeM.

Therapeutic drug monitoring to optimize psychopharmacotherapy in children and adolescents - Update and guidelines for practice Abstract. Despite the improved evidence base, many uncertainties remain in child and adolescent psychiatric pharmacotherapy about the efficacy and tolerability of drugs, which are often prescribed off-label or in combination therapy in this age group. Because medium- to long-term use is unavoidable in many cases, clinicians should minimize adverse drug reactions as far as possible and tailor an effective dosage to the individual characteristics of the patient. Not only are children and adolescents particularly vulnerable to certain adverse drug effects, they are also exposed to iatrogenic risks from dosing or application errors, which can lead to under- or overdosing with correspondingly negative effects on the success of the therapy. In addition to determining a strict indication, it is therefore essential to establish precise dosage and systematic monitoring of the safety of the psychopharmacotherapy. This article introduces therapeutic drug monitoring as a useful clinical tool and describes how its correct application in practice can improve the efficacy as well as the safety and tolerability of psychotropic therapy in children and adolescents for the immediate benefit of patients. Keywords: Psychopharmacotherapy, adverse drug reactions, pharmacovigilance, therapeutic drug monitoring, quality assurance.

Anxiety and Depression in Transition - Desiderata for Improved Care and Research: Results of the Joint Task Force Transition of DGPPN and DGKJP Abstract. Affective disorders (e. g., anxiety, depression) frequently begin during adolescence. Yet therapeutic approaches during adolescence differ in some respects from those employed during adulthood. During the transition from adolescence to adulthood, there is a high risk of discontinuation of therapeutic treatment, which may consequently affect integration in employment. There is a need for age-specific therapeutic strategies that address the relevant issues of adolescents as well as the presently unmet needs in research and treatment for this specific population.

Polypharmacy of psychotropic drugs in child and adolescent psychiatry in Germany - rather the rule than the exception Abstract. Background: Polypharmacy increases the risk of interactions and enhances the chance of adverse drug reactions (ADRs). Hence, child and adolescent psychiatrists generally try to avoid polypharmacy with psychotropic drugs. However, only little data regarding the frequency of polypharmacy in child and adolescent psychiatry are available. This study analyzes clinical data on polypharmacy and the possible association with a higher risk of ADRs in Germany, with a focus on antidepressants and antipsychotics. Methods: We investigated a total of 940 datasets from descriptive studies on therapeutic drug monitoring (TDM) of pediatric patients treated with different psychotropic drugs. Results: The frequency of polypharmacy ranged up to 45.6 % (escitalopram) and 72.1 % (olanzapine). In 17.4 % of the cases, polypharmacy consisted of four or more psycho-/neuropharmacological substances. No increased incidence of ADRs was reported with polypharmacy of antipsychotics compared to monotherapy. Polypharmacy with sertraline was associated with a higher number of ADRs. Discussion and Conclusion: There is a high prevalence of polypharmacy with psychotropic drugs in child and adolescent psychiatry in Germany. Conclusions concerning individual drugs should be drawn with care since the subsample sizes were relatively small. However, our results do provide an indication of the prevalence of polypharmacy, although the validity of the data is limited. There is an urgent need to analyze data from larger and more homogeneous groups under more controlled conditions.

Introduction: Researchers have repeatedly discovered an association between depression and autonomic cardiac dysregulation in adults. However, corresponding data concerning minors are still rare. Method: For this exploratory, cross-sectional study, we included N = 43 minors (age range 9-17 years). The subjects were depressive subjects with or without antidepressant medication ( N = 23) or healthy control children (HC) ( N = 20). We assessed several indices of cardiac functioning using long-term electrocardiogram data (mean heart rate, HR, and several parameters of heart rate variability, HRV). We hypothesized that increased HR and reduced HRV are associated with depressive disorders. Furthermore, we assessed the impact of age, sex, and antidepressant medication on HR and HRV. Results: When sex and age were controlled for, HR was significantly increased in depressive minors compared to HC. However, our preliminary data suggest that this might not be the case in medicated patients, and there were no differences between groups regarding HRV parameters. There was no significant correlation in the whole sample between severity of depression and both HR and HRV. In the subsample of patients with depression, antidepressant medication was associated with lower HR and higher indices of HRV. Conclusion: The data indicate an association between depression and altered autonomic cardiac regulation, which can already manifests in minors.

The use of selective serotonin reuptake inhibitors (SSRIs) like citalopram in the clinical treatment of depressive symptoms in children and adolescents has become increasingly common, although application is mostly off-label. The increasing number of prescriptions is not only due to their good efficacy, but also due to their good tolerability and the comparatively low risk in cases of intoxication. However, there is discussion about the cardiac safety of overdose ingestion of citalopram. Here, we report in detail on an adolescent with depressive symptoms who used 800 mg of citalopram in order to attempt suicide. In contrast to other case reports in adults, our patient showed only mild neurological symptoms and no cardiac toxicity or symptoms of a serotonin syndrome, despite a high citalopram blood concentration measured about two hours following ingestion of citalopram (633 ng/ml; therapeutic reference range for adults 50-110 ng/ml).

Does methylphenidate cause liver damage? An analysis of ad hoc reports to the "Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)" Abstract. Ad hoc reports to the "Bundesinstitut für Arzneimittel und Medizinprodukte" (BfArM, the German Federal Institute for Drugs and Medical Devices) were analyzed concerning liver injuring stemming from therapy with methylphenidate (MPH). Clinical criteria were used to assess suspected cases of causal association. The BfArM database on adverse drug reactions (ADRs) recorded suspected cases from Germany over the period from 1 January 2006 to 23 May 2016. Using the Standardized MedDRA Queries (SMQ) search strategy, we searched the database for "MPH" and its potential ADRs "Hepatic Disorder." The ad hoc reports were checked for completeness and assessed clinically according to the Uppsala Monitoring Centre criteria. 60 suspected cases of liver damages by MPH were recorded in the database. In 15 thereof, an assessment was not possible because of insufficient documentation; in 25 cases, a link between the intake of MPH and the occurrence of liver injury was considered "unlikely." A "possible" causality was assessed in 11 cases, a "probable/likely" causality in 9 cases: 1 patient with fulminant hepatitis, 1 with increased size of benign liver tumor, and 18 cases of (reversible) hepatic enzyme elevation. According to our evaluation, MPH is well-tolerated with regard to liver and gall bladder diseases. For patients with hepatic impairment or other risk factors, regular monitoring of liver values is recommended.

Objective: A recent Cochrane review published by O. J. Storebo and colleagues (2015) raised substantial doubts about the benefit from stimulant medication with methylphenidate in the treatment of childhood ADHD due to the overall poor quality of studies. The systematic review thus contradicts all previous reviews and meta-analyses., Method: We here detail various examples of errors, inconsistencies, and misinterpretations in the review which led to false results and inadequate conclusions., Results: We demonstrate that the study selection is flawed and undertaken without sufficient scientific justification resulting in an underestimation of effect sizes, which, furthermore, are inadmissibly clinically interpreted. The methodology of the assessment of bias and quality is not objective and cannot be substantiated by the data., Conclusions: Cochrane reviews lay claim to a high scientific quality and substantial relevance for evidence-based clinical decisions. The systematic review by Storebo and colleagues (2015) illustrates that, despite adhering to strict standards and high-quality protocols, even Cochrane works should be critically read and verified, sometimes with surprising results.

Rational pharmacotherapy is a challenging task in child and adolescent psychiatry. Increasing prescription numbers contrast with the uncertainties of safety and efficacy issues. The lack of clinical (authorization) trials often implies a non- age-specific use of drugs. However, young patients show particular metabolic conditions and a higher vulnerability for adverse drug reactions. Thus it seems mandatory to create age-specific pharmacological data about efficacy and safety of psychotropic drug use in minors. Legislation authorities became aware of this situation and introduced European and national scientific pharmacovigilance regulations and programmes accordingly in order to continuously evaluate the benefit-risk-ratio, detect, collect, minimize, and prevent adverse effects of drugs by appropriate measures, e.g., therapeutic drug monitoring. In this paper the principles and needs of pharmacovigilance in child and adolescent psychiatry are discussed. Furthermore a large multicenter clinical trial («TDM-VIGIL»), funded by the German Federal Institute for Drugs and Medical Devices, is presented, which appeals to collect epidemiological prescription and safety data of psychotropic drugs in children and adolescents using an internet-based data infrastructure (patient registry).

Background: Atopic dermatitis (AD) and attention-deficit/hyperactivity disorder (ADHD) are frequent paediatric conditions with high medical relevance. A possible relationship between atopic diseases (i.e., AD, asthma, and allergic rhinitis) has long been discussed, but convincing evidence is still missing., Methods: We investigated the relationship between AD and ADHD in two cross-sectional studies and in two birth cohort studies considering lifestyle factors, environmental factors, and atopic comorbidities as potential confounders. To quantify the strength of association between AD and ADHD, data from the four epidemiologic studies were summarized by means of a meta-analysis. Odds ratios (OR) were pooled for the association between prevalent or previous AD and prevalent ADHD from the four studies adjusted for age, sex, and atopic comorbidity (allergic rhinitis, asthma)., Results: The epidemiologic studies conducted consistently indicate an association between AD and ADHD which is independent of environmental exposures and other comorbidities. Particularly infant AD appears to be associated with later development of ADHD symptoms. Sleeping problems due to AD are suggested as playing an important role for the observed association between AD and ADHD. The pooled OR (95 % confidence interval (95 %CI)) for the association between AD and ADHD was 1.43 (1.25-1.64)., Discussion: Four new epidemiologic studies consistently indicate a positive association between AD and ADHD. Compared to children without AD, children with previous or prevalent AD have an approximately 43 % increased risk to be diagnosed with ADHD or to display clinical ADHD symptoms. Following our findings, the biological mechanisms underlying the observed comorbidity between AD and ADHD require further investigation in order to subsequently develop targeted therapeutic and preventive strategies.

Objectives: This study assesses the cognitive and emotional empathic competence in groups of children and adolescents with psychiatric disorders compared to a nonclinical control group. Subjective and objective diagnostic measures were employed., Methods: A total of 96 boys were tested: 20 with attention-deficit/hyperactivity disorder (ADHD) predominantly inattentive subtype (ADHD-I); 20 with ADHD combined subtype (ADHD-C); 20 with conduct disorder (CD); 36 healthy boys (control group; CG). Mean age was 12.0 years (SD = 2.36). As aspects of cognitive and emotional empathy emotional reactivity, we tested emotion recognition and perspective taking with subjective questionnaires and objective tasks, using as subjective questionnaires the Interpersonal Reactivity Index (IRI; Davis, 1983) and the Index of Empathy for Children and Adolescents (IECA; Bryant, 1982). As objective tasks, we adopted the Empathy Response Task (ERT; Ricard & Kamberk-Kilicci, 1995) and a task measuring emotion recognition according to Buitelaar et al. (1999)., Results: The CG outperformed participants with ADHD-C and CD in objective tasks assessing perspective taking, particularly when complex tasks were applied as stimuli. Children with ADHD-I showed significantly more emotional empathy than boys with ADHD-C when presented with simple tasks. No group differences were found for emotion recognition and subjective questionnaires., Discussion: Deficits in perspective taking and emotional empathy were found for children with ADHD-C and CD, largely in accordance with the literature. Similar to the processing of cognitive information, the processing of emotional information seems to differ in ADHD subtypes. Objective tasks and tasks with a high ecological validity seem suitable for the measurement of empathy.

Objective: As a presumptive side effect, a lowered seizure threshold due to medication with methylphenidate remains controversial. The pilot study at hand addresses the experimental verification of this claim. Furthermore, quantitative effects of methylphenidate treatment on EEG are measured., Method: The EEGs of 15 patients with ADHD aged 6 to 14 years were acquisitioned. Diagnosis was made according to multi-axial diagnostic procedures and in observance of all ICD-10 criteria. In order to evaluate the electrophysiological effects of methylphenidate, the EEG-data were analysed with regard to the composition of the frequency spectrum and the occurrence of pathological EEG-alterations., Results: The analysis of EEG data prior to and subsequent to medication with methylphenidate showed an increase of occipital alpha-activity, whereas of delta-theta-activity was reduced. Beta-activity increased in the central region and showed a trend towards a frontal increase. Neither before nor after treatment with methylphenidate could pathological potentials be detected., Conclusion: The results support the common view in the existing literature that methylphenidate does not lower the seizure threshold. Rather its effect on electrophysiological parameters can be described as a normalisation in terms of an acceleration of the occipital rhythm.

Objectives: Considering a prevalence of three to ten percent migraine in children is not a rare disease. Visual auras as a characteristic of classical migraine are often described in literature. However, most of these are primary hallucinations, whilst descriptions of complex hallucinations are barely to find. As far as we know this work describes the youngest age, at which complex hallucinations occurred in migraine attacks. Reviewing the existing literature possible pathophysiologic mechanisms and differential diagnosis are discussed., Methods: We introduce a case-report of a 10-year old-patient who reports a complex visual hallucination during a migraine attack. Symptoms, history and diagnostic measures are described. In differential diagnosis to a migrainous aura the "Alice-in-Wonderland-syndrome", "Lilliputian hallucinations", the basilar migraine and epilepsy are discussed., Results: For complex hallucinations an analogical pathomechanism to primary hallucinations in migraine can be assumed. The great variety of the migrainous aura is pointed out.