Pharmacotherapy for ADHD in children and adolescents: A summary and overview of different European guidelines.

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.

[Depressive and anxiety symptoms in hereditary connective tissue disorders : case description and systematic literature review]. / Depressieve en angstklachten bij erfelijke bindweefselaandoeningen: casus en systematisch literatuuroverzicht.

Hereditary connective tissue disorders are a broad group of congenital disorders that are characterized by a pathological weakness of the connective tissue as a result of an incorrect genesis, leading to multisystem complaints. We describe a 14-year-old patient with the hereditary connective tissue disorder Loeys-Dietz syndrome who was admitted to a child psychiatric crisis unit because of depressive and anxiety symptoms. A systematic literature search was carried out to analyze the prevalence of depressive and anxiety symptoms in individuals with hereditary connective tissue disorders Loeys-Dietz syndrome, Ehlers-Danlos syndrome and Marfan syndrome, to identify a possible association between these disorders and explanations for this. We conclude that there is an increased incidence of depression and anxiety symptoms in which pain, fatigue, social support and functioning, quality of life and functional limitations seem to play a role. There is a need for further research to determine exactly which factors contribute and how these can be targeted in prevention and treatment.

[An evidence-based update of the ADHD care pathway in Belgium: a systematic literature review]. / Evidence-based update van het Belgische ADHD-zorgpad: een systematische review.

BACKGROUND: The ADHD care path (www.ADHD-traject.be) is a web tool that provides evidence-based advice for the diagnosis and treatment of ADHD according to the standards for certified care instruments. An update of the 2016 instrument was imminent. AIM: This study aims to test the content of the care path against (inter)national quality guidelines and to update them to meet the current transparency requirements. METHOD: Part A consisted of a systematic literature search performed (PRISMA ) to identify (clinical) guidelines for ADHD and to assess their quality with the AGREE II instrument. Part B consisted of two phases: a full clinical content update based on the results from Part A, followed by a peer review.. RESULTS: Of the 29 guidelines identified, 12 met the pre-established inclusion criteria, of which 2 were excluded from part B of the study after quality assessment. Numbered endnotes made a direct link between the international guidelines and the advice in the care path, clinical content changes were made, then a consensus version was reached through peer review. CONCLUSION: This is the first scientific contribution reporting on the update of a care instrument based on both a systematic literature review and a peer review with transparency on the clinical content changes. Based on this, the care path was certified according to the Belgian CEBAM standards.

[Meta-analysis: effect of chemotherapy on intelligence of children treated for leukemia]. / Meta-analyse: intelligentie van kinderen na chemotherapie wegens leukemie.

BACKGROUND: Leukemia is the most common pediatric malignancy. Acute lymphoblastic leukemia (ALL) is the most commonly observed subtype. AIM: To assess cognitive functioning in children and adolescents with ALL post-treatment: chemotherapy-only (CT-only) or in combination with radiation therapy (CTRT). METHODS We searched in PubMed and PsycINFO (OvidSP). Relevant data were analyzed using statistical program Comprehensive Meta-Analysis (version 2). RESULTS: 44 studies were included in the overall meta-analysis with a total of 5059 patients. A weighted mean IQ of 100.1 (95% CI 99.1-101.0) was found overall after ALL treatment. In subanalyses, we found for CT-only a weighted mean IQ of 100.7 (95% CI: 99.5-101.9) and for CTRT-treatment a weighted mean IQ of 98.2 (95%100.7 (95% CI: 96.3-100.3). There was no significant difference from the normative control (mean: 100.0; SD: 15). CONCLUSION: No significant cognitive sequelae were shown in childhood survivors of leukemia who were exposed to either CT-only or CTRT therapy. Prospective studies are needed with inclusion of pre-and post-treatment IQ measurements, ideally compared to age and socio-economic status matched control groups.

[Effectiveness of guanfacin on comorbid disorders in children and adolescents with adhd: a systematic literature review]. / Effectiviteit van guanfacine bij comorbide stoornissen bij kinderen en jongeren met ADHD: systematische literatuurstudie.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a frequently occurring problem in child and adolescent psychiatry. Most prevalent comorbid disorders are oppositional defiant behavior, tics, autism spectrum disorder, anxiety and depression. Stimulants are the first pharmacological choice. Recently, long-acting guanfacin became available in Belgium and the Netherlands.
AIM: To investigate the efficacy of guanfacin on comorbid symptoms in ADHD.
METHOD: A systematic search in Medline and Cochrane databases for randomized controlled trials in which the effect of guanfacin on comorbid symptoms is evaluated.
RESULTS: Guanfacin had an effect on autism symptoms, oppositional defiant symptoms and possibly on tics in children and adolescents with adhd. On anxiety symptoms, no effect was reported. The effect on depression needs to be further investigated. The side effects of guanfacin are similar in comorbid disorders and pure ADHD.
CONCLUSION: Guanfacin is a treatment option for ADHD in children and adolescents with comorbid autism or behavioural symptoms and possibly also tics, as it has a demonstrated effect on these comorbid features. Further research is necessary in order to decide on the preference for a particular medication in ADHD with these various comorbid disorders.

[Psychotic symptoms as a side-effect of omeprazole]. / Psychotische symptomen als bijwerking van omeprazol.

A 12-year-old girl with no psychiatric history developed psychotic symptoms, including formal thought disorder and delusional ideas after omeprazole was initiated. Given the co-occurrence of omeprazole initiation and the start of these symptoms, omeprazole was discontinued and replaced by ranitidine which led to immediate symptom reduction followed by complete remission. Although the proton pump inhibitor (ppi) omeprazole is considered safe and is commonly prescribed, it can cause rare major psychiatric side-effects. Despite conducting a literature search to uncover a possible causal mechanism to explain these side-effects, no conclusive explanatio was found.

[N-of-1 trials in child and adolescent psychiatry: a closer look at stimulants]. / N=1-trials in de kinder- en jeugdpsychiatrie: gebruik van stimulantia bij ADHD.

BACKGROUND: An N-of-1 trial is a clinical trial studying the response of an individual to a particular intervention or different interventions in an objective, systematic way. AIM: To evaluate both the applications and the methodology of N-of-1 trials in child and adolescent psychiatry. METHOD: A systematic review using PubMed and Embase assessing N-of-1 trials published during the period 1986 - July 2016 with the following key-word: 'N-of-1'. RESULTS: 20 articles were included. All articles used N-of-1 trials to evaluate the effect of stimulant medications in children and adolescents with ADHD. Most articles recommended the use of the N-of-1 methodology in clinical practice, despite the large variation in methodology and in outcome interpretation of N-of-1 trials. The 20 articles didn't meet the current quality standards for N-of-1 trials. CONCLUSION: Despite the advantages of N-of-1 trials, the applications in child and adolescent psychiatry turn out to be rather limited and specific. N-of-1 trials have more to offer regarding both clinical practice and research in child and adolescent psychiatry. If the methodological recommendations are sufficiently met, N-of-1 trials could provide a useful and applicable tool for the child- and adolescent psychiatrist to offer individual patient care.

[Hashimoto encephalopathy as explanation of psychotic symptoms in an adolescent]. / Hashimoto-encefalopathie als verklaring voor psychotische symptomen bij een adolescent.

Hashimoto encephalopathy (he) is a rare disorder with a great diversity in clinical presentation of neurological and/or psychiatric symptoms. We describe a case of Hashimoto thyroiditis with hypothyroidism and Hashimoto encephalopathy in a fifteen-year-old boy who was referred to a child and adolescent psychiatrist due to a suspicion of a psychotic episode. Patient recovered after treatment with levothyroxine and corticosteroids.

[Trends in antipsychotics use by Belgian children and adolescents between 2005 and 2014]. / Het gebruik van antipsychotica bij kinderen en jongeren in België, 2005-2014.

BACKGROUND: Antipsychotics are frequently prescribed for a wide range of psychiatric and non-psychiatric indications. Over the last few years there has been a marked increase in the use of antipsychotics, in European and non-European countries. The use has also increased in children.
AIM: To assess trends in the sales of antipsychotics for Belgian children and adolescents (7 to 17 years old) between 2005 and 2014.
METHOD: We used data supplied by Farmanet, the official Belgian organisation responsible for collecting information about the prescription behaviour of doctors in Belgium.
RESULTS: Between 2005 and 2014 there was a 53% increase in the number of prescriptions for antipsychotics issued by doctors in Belgium. This period also saw a 75.5% increase in the number of prescriptions for antipsychotics issued for the treatment of children and adolescents. There was a particularly large increase in the number of prescriptions for aripiprazole, the increase being only very slightly compensated by a simultaneous decrease in the number of prescriptions issued for other antipsychotics. In 2014, 21 different antipsychotics were prescribed for children, the majority of these prescriptions being for risperidone and aripiprazole. A large proportion of antipsychotics are used off-label. In exceptional cases, antipsychotics were prescribed for children under the age of six, and even for children younger than two.
CONCLUSION: Between 2005 and 2014 there was an increase in the number of prescriptions for antipsychotics issued for children and adolescents in Belgium. During that period of time there was a similar increase in the use of antipsychotics by children and adolescents in other European and non-European countries. It is not clear whether these increases are justified.

[A comparative study of the structural stigmatisation of ADHD and autism spectrum disorder in Flemish newspapers]. / Vergelijkend onderzoek naar structureel stigma bij ADHD en autismespectrumstoornis in de Vlaamse dagbladen.

BACKGROUND: Children and adults with adhd and autism spectrum disorder (asd) often find themselves being stigmatised. There is ample evidence of public stigma, but much less is known about negative coverage in the media, a phenomenon that can be regarded as a form of structural stigma.
AIM: To explore the different types of structural stigma that characterise the coverage of adhd and asd in Flemish newspapers.
METHOD: We used the online databases of seven Flemish newspapers in order to select articles on adhd (n=772) and asd (n=1940) published between 2010 and 2014. We divided these articles into separate categories relating to the domain of coverage (e.g. symptomatology, epidemiology, medical treatment) and valence (i.e. positive, neutral and negative).
RESULTS: We found significantly more negative than neutral/positive coverage of adhd than of asd (or 2.1). This finding was most striking in the domains of symptomatology (or 8.42), diagnostics (or 2.28) and medical treatment (or 9.40). Furthermore, with respect to articles specifically on adhd, the title of the article was significantly more negative than the actual message in the main article itself (χ2(2)=22.454, p < 0.001).
CONCLUSION: These findings show that Flemish newspapers need to adjust and correct their negative and inaccurate portrayal of symptomatology, diagnostics and treatment of adhd and, to a lesser extent, of asd. Readers of these newspapers also need to be given a less negative impression of adhd and asd.

[The stigmatising of schizophrenia and autism in the Flemish daily papers]. / Stigma rond schizofrenie en autisme in de Vlaamse dagbladen.

BACKGROUND: A considerable social stigma is attached to many types of psychiatric disorders. However, research also shows that there are differences in the degree of social stigma attached to psychiatric disorders. There is evidence that the portrayal of schizophrenia in the media is particularly negative. AIM: To compare the degree of stigma in reporting of autism and schizophrenia in the Flemish daily newspapers. METHOD: Via the websites of the seven Flemish daily newspapers, we searched for all articles published between 2008 and 2012 containing the keywords autism/autist(ic) and schizophrenia/schizophrenic. The collected articles (n = 4,181) were then graded to their stigmatising content. RESULTS: In the collected articles the coverage of autism was mostly positive, whereas the coverage of schizophrenia was predominantly negative. The contrast between the reporting on autism and on schizophrenia was very substantial (p < 0.0001) and the negative coverage of both disorders increased over time. CONCLUSION: The social stigma attached to schizophrenia is poignantly reflected in the Flemish newspapers. The fact that a disorder such as autism, which has many features in common with schizophrenia, is depicted in a much more favourable way than schizophrenia indicates that a more positive image of schizophrenia is not only desirable but also achievable.

Registration of aggressive incidents in an adolescent forensic psychiatric unit and implications for further practice.

Although aggression is part of daily life in psychiatric units for adolescents, empirical data on its prevalence are sparse. Only few studies have described prevalence of aggressive incidents in adolescent psychiatric wards, and data in forensic psychiatric care are even more limited. Available studies reported high prevalence rates of aggression, ranging from 0.4 to 2.4 incidents of aggression per day across (forensic) child and adolescent psychiatric units. Between 27 and 78 % of all admitted youth committed an aggressive act. In this study, we collected systematically registered data of all aggressive incidents from the first 2 years (2010-2012) on a newly established forensic adolescent psychiatric unit, which used a formal aggression management program embedded in the social competence model, which is based on early intervention in the 'chain of behavior' to prevent any further escalation. The inclusion of also minor aggressive incidents is unique in the literature and the clinical relevance is highlighted. A mean of one incident a day took place, with each adolescent involved in at least one incident. Notably, 1.7 aggressive incidents per month made seclusion of restraint use necessary. Based on the social competence theory, the aggression management model suggests intervening early in the cascade of aggression, in order to prevent further escalation and reduce the need for intrusive interventions. Evidence supported that aggression is a contextual event, as external factors clearly influence the incidence of aggression. Aggression management should be built on both relational and structural security.

[Managing aggression in a forensic psychiatric unit for adolescents: literature review and clinical implementation]. / Agressiebeleid op een forensische psychiatrische unit voor adolescenten; literatuuroverzicht en implementatie in de praktijk.

BACKGROUND: Aggressive incidents are part and parcel of everyday life in a forensic psychiatric unit for adolescents. AIM: To review the literature about the prevalence of aggressive incidents and about aggression management policy in (forensic) child and adolescent psychiatry and to explain and elaborate the aggression management protocol in a newly established unit. METHOD: The literature was reviewed systematically using PubMed and PsycINFO in order to locate studies in English and Dutch published since 1990. RESULTS: Only 10 publications reported prevalence data on aggressive incidents in child or adolescent psychiatric units. Literature about concrete policy guidelines was almost non-existent. 27% to 78% of the youngsters had been involved in some kind of aggression. The lack of clear definitions and the differences in the research designs made a reliable comparison impossible. CONCLUSION: To date, there is no evidence that a greater number of aggressive incidents occur in a forensic psychiatric unit for adolescents than in a regular adolescent psychiatric unit. Further research into both the prevalence and the characteristics of incidents is required in order to provide cues for a good policy. This policy will need to include structural and relational security measures that are firmly supported by the systematic registration of incidents and by continuous risk assessment.

Within-subject variability during spatial working memory in children with ADHD: an event-related potentials study.

Working memory (WM) dysfunction and increased within-subject variability are known issues in attention deficit/hyperactivity disorder (ADHD) patients. Little is known about the electrophysiological characteristics of this variability. We evaluated behavioral and electrophysiological within-subject variability taking developmental aspects into account in a group of ADHD patients. Multichannel (n = 31) event-related potentials (ERP) were measured during a visuo-spatial backmatching task; 44 children (8-16 years old) were tested: 22 children with ADHD, combined (n = 17) and inattentive (n = 5) type, and 22 age- and intelligence-matched control children. One-backmatching (BM1) and two-backmatching (BM2) tasks were performed. Classical behavioral parameters and target and nontarget ERP were compared between groups. In addition, motor response variability and ERP amplitude variability were studied. Age-related changes in both motor response and ERP amplitude variability were analyzed in each group. Attention deficit/hyperactivity disorder children made more commission errors, which was more pronounced in the difficult (BM2) task. No difference between groups was found in ERP amplitude and in motor response variability. However, ADHD patients had higher ERP amplitude variability, which was again more pronounced in the difficult WM task. A delayed maturation of amplitude variability was seen in ADHD patients with a slower than in controls decrease in variability with age. This amplitude variability was correlated with the number of commissions, but in an opposite way for ADHD and control children. Our findings indicate an impaired visuo-spatial WM processing in ADHD children with greater ERP amplitude variability compared to controls. Our results also support the view of a delayed cortical development of visuo-spatial WM circuits in this disorder.

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.

[Omega-3 and omega-6 fatty acids in the treatment of children and adolescents with ADHD]. / Omega-3- en -6-vetzuren bij de behandeling van kinderen en jongeren met ADHD.

UNLABELLED: Background There is a growing trend towards the use of alternative forms of treatment for attention deficit hyperactivity disorder (adhd), such as the food supplements omega-3 and omega-6 fatty acids. AIM: To study biochemical aspects, important hypotheses regarding the role of these fatty acids in brain development, the mode of operation and research results concerning the effectiveness of treating adhd with these supplements. METHOD: A Medline search was performed using the Mesh-term 'fatty acids' and the search terms 'omega-3 and omega-6 fatty acids' and 'attention deficit hyperactivity disorder'. results Some rct's (randomised controlled trails) involving children with adhd didn't show any improvement after treatment with omega-3 and omega-6 fatty acids. Some other rct's, however, did show a reduction in adhd symptoms and learning difficulties, but the children concerned had not been officially diagnosed with adhd. A recent rct showed a substantial reduction in adhd symptoms in children with the inattentive type of adhd and in children with adhd and comorbid problems. CONCLUSION: There are indications that there is a theoretical rationale for the effectiveness of fatty acids in the treatment of adhd; research is ongoing. At the moment, however, treatment of adhd with omega-3 and omega-6 fatty acids is not recommended because it does not qualify as being evidence-based.

[The prevalence of ADHD in the Belgian general adult population: an epidemiological explanatory study]. / ADHD in de Belgische volwassen bevolking; een epidemiologische exploratieve studie.

BACKGROUND: Despite growing interest in attention deficit and hyperactivity disorders (ADHD) in adults in Belgium, little is known about its prevalence in the Belgian general population. AIM: To estimate the prevalence of ADHD in adults (aged 18 to 44) in Belgium, to study its comorbidity with other mental disorders and its impact on daily living and to find out the extent to which professional help is sought. METHOD: A representative sample (n = 486) taken from the Belgian population was studied by means of an ADHD screening questionnaire which is included in the third version of the Composite International Diagnostic Interview. RESULTS: The prevalence of ADHD in adults in the Belgian population was estimated to be 4.1%. The disorder started in early childhood (median age 7 years) and developed fastest between the ages of 7 and 9. ADHD was comorbid with anxiety disorders (adjusted odds ratio: 7.5; 95% ci: 1.2-45.2) and alcohol-related disorders (adjusted odds ratio: 7.6; 95% ci: 1.1-52.5), and results in a suboptimal daily functioning on about 7.7 days a month. Only one person in five had sought professional help in the 12 month period prior to the screening test. CONCLUSION: This is the first study to estimate the prevalence of ADHD in adults in Belgium. ADHD is a relatively frequent disorder that starts early in life, and has a considerable impact on the way in which an individual functions in daily life. In spite of this, few persons with this disorder seek professional help.

Prenatal life and post-natal psychopathology: evidence for negative gene-birth weight interaction.

BACKGROUND: Many studies suggest that pregnancy and birth complications (PBCs) are environmental risk factors for child psychopathology. However, it is not known whether the effects of PBCs occur independently of genetic predisposition. The current study examined the possibility of gene-environment interaction in a twin design. METHOD: The East Flanders Prospective Twin Survey prospectively records the births of all twin pairs born in East Flanders, Belgium. The current study included 760 twin pairs aged 6-17 years. Multilevel regression analysis was used to assess the effects of several PBCs collected around the time of birth. Using structural equation modelling, ACE models assuming additive genetic (A), shared environmental (C) and unique environmental (E) influences, were compared in order to examine whether the contribution of genetic factors to parent-rated child problem behaviour varied as a function of exposure to dichotomously and continuously defined PBCs. RESULTS: A main independent effect of lower birth weight, corrected for gestational age (small for gestational age--SGA), on child problem behaviour was found. In addition, there was an interaction between genetic influence and SGA, in that being smaller for gestational age resulted in less influence of additive genetic factors on individual differences in problem behaviour. CONCLUSIONS: Results are suggestive of negative gene-birth weight interaction. Children who are SGA are less sensitive to the genetic effects, and those with high genetic vulnerability are less sensitive to the effects of being SGA in bringing about post-natal mental health effects.