Medication adherence and persistence in children and adolescents with attention deficit hyperactivity disorder (ADHD): a systematic review and qualitative update.

Low medication-adherence and persistence may reduce the effectiveness of ADHD-medication. This preregistered systematic review (PROSPERO CRD42020218654) on medication-adherence and persistence in children and adolescents with ADHD focuses on clinically relevant questions and extends previous reviews by including additional studies. We included a total of n = 66 studies. There was a lack of consistency in the measurement of adherence/persistence between studies. Pooling the medication possession ratios (MPR) and using the most common adherence definition (MPR ≥ 80%) indicated that only 22.9% of participants had good adherence at 12-month follow-up. Treatment persistence on medication measured by treatment duration during a 12-month follow-up averaged 170 days (5.6 months). Our findings indicate that medication-adherence and persistence among youth with ADHD are generally poor and have not changed in recent years. Clinicians need to be aware that various factors may contribute to poor adherence/persistence and that long-acting stimulants and psychoeducational programs may help to improve adherence/persistence. However, the evidence to whether better adherence/persistence contributes to better long-term outcomes is limited and requires further research.

The management of ADHD in children and adolescents: bringing evidence to the clinic: perspective from the European ADHD Guidelines Group (EAGG).

ADHD is the most common neurodevelopmental disorder presenting to child and adolescent mental health, paediatric, and primary care services. Timely and effective interventions to address core ADHD symptoms and co-occurring problems are a high priority for healthcare and society more widely. While much research has reported on the benefits and adverse effects of different interventions for ADHD, these individual research reports and the reviews, meta-analyses and guidelines summarizing their findings are sometimes inconsistent and difficult to interpret. We have summarized the current evidence and identified several methodological issues and gaps in the current evidence that we believe are important for clinicians to consider when evaluating the evidence and making treatment decisions. These include understanding potential impact of bias such as inadequate blinding and selection bias on study outcomes; the relative lack of high-quality data comparing different treatments and assessing long-term effectiveness, adverse effects and safety for both pharmacological and non-pharmacological treatments; and the problems associated with observational studies, including those based on large national registries and comparing treatments with each other. We highlight key similarities across current international clinical guidelines and discuss the reasons for divergence where these occur. We discuss the integration of these different perspective into a framework for person/family-centered evidence-based practice approach to care that aims to achieve optimal outcomes that prioritize individual strengths and impairments, as well as the personal treatment targets of children and their families. Finally, we consider how access to care for this common and impairing disorder can be improved in different healthcare systems.

Medication Adherence in Adolescents with Psychiatric Disorders.

Objective: This study investigates whether adolescents' adherence to psychotropic medication is associated with demographic and socioeconomic factors, and to what extent parents' assessments of their offspring's attitudes toward treatment correspond with the adolescents' self-report. Methods: This study is part of the multicenter SEMA study (Subjective Experience and Medication Adherence in Adolescents with Psychiatric Disorders). Adolescents' subjective attitudes toward medication and their adherence were assessed using the patient and parent versions of the QATT (Questionnaire on Attitudes Toward Treatment) and the MARS (Medication Adherence Rating Scale). Furthermore, we collected socioeconomic and demographic data. Results: Of the n = 75 adolescents included in the study, n = 45 (60 %) were classified as completely adherent. Patients receiving monotherapy were more often completely adherent than those receiving a combination of different medications. There was no statistically significant association between adherence and demographic or socioeconomic factors. Consensus between adolescents and their parents regarding adolescents' attitudes toward treatment ranged from slight (κ = 0.157) to fair (κ = 0.205). Conclusion: Incomplete medication adherence in adolescents with psychiatric disorders is a common phenomenon and still poorly understood. Demographic and socioeconomic factors do not seem to be relevant in this respect. However, adolescents' subjective attitudes towards medication, which parents are presumably unable to adequately assess, warrant more careful consideration in future research.

Practitioner Review: Current best practice in the use of parent training and other behavioural interventions in the treatment of children and adolescents with attention deficit hyperactivity disorder.

BACKGROUND: Behavioural interventions are recommended for use with children and young people with attention deficit hyperactivity disorder (ADHD); however, specific guidance for their implementation based on the best available evidence is currently lacking. METHODS: This review used an explicit question and answer format to address issues of clinical concern, based on expert interpretation of the evidence with precedence given to meta-analyses of randomised controlled trials. RESULTS: On the basis of current evidence that takes into account whether outcomes are blinded, behavioural intervention cannot be supported as a front-line treatment for core ADHD symptoms. There is, however, evidence from measures that are probably blinded that these interventions benefit parenting practices and improve conduct problems which commonly co-occur with ADHD, and are often the main reason for referral. Initial positive results have also been found in relation to parental knowledge, children's emotional, social and academic functioning - although most studies have not used blinded outcomes. Generic and specialised ADHD parent training approaches - delivered either individually or in groups - have reported beneficial effects. High-quality training, supervision of therapists and practice with the child, may improve outcomes but further evidence is required. Evidence for who benefits the most from behavioural interventions is scant. There is no evidence to limit behavioural treatments to parents with parenting difficulties or children with conduct problems. There are positive effects of additive school-based intervention for the inattentive subtype. Targeting parental depression may enhance the effects of behavioural interventions. CONCLUSIONS: Parent training is an important part of the multimodal treatment of children with ADHD, which improves parenting, reduces levels of oppositional and noncompliant behaviours and may improve other aspects of functioning. However, blinded evidence does not support it as a specific treatment for core ADHD symptoms. More research is required to understand how to optimise treatment effectiveness either in general or for individual patients and explore potential barriers to treatment uptake and engagement. In terms of selecting which intervention formats to use, it seems important to acknowledge and respond to parental treatment preferences.

Non-adherence to Psychotropic Medication Among Adolescents - A Systematic Review of the Literature.

Introduction: Whether patients take their medication as prescribed is of increasing importance in adolescent psychiatry since both the number of efficacious pharmaceutical treatments and the rate of prescriptions of psychotropic compounds are on the rise. Previous research showed high rates of medication nonadherence among both adolescents with medical disorders and adult patients with psychiatric disorders. Methods: The present review was performed according to PRISMA guidelines and evaluates existing scientific literature concerning adherence to psychotropic medication among adolescents. The goal was to determine rates of nonadherence in this age group as well as the factors associated with it. Therefore, we conducted a comprehensive literature search of PubMed from its inception until 15 September 2015 using the keywords "adherence," "compliance," "adolescent," and "psychotropic medication." Results: A total of 607 pertinent articles were collected and screened; 15 publications were selected for detailed review. The studies differed, among other things, regarding sample characteristics, medication type, and indications. Furthermore, the definitions of what constitutes nonadherence and the methods used to assess it varied widely. Nonadherence rates ranged from 6 % to 62 % (median 33 %). Conclusions: Nonadherence to psychotropic medication is a clinically relevant problem among adolescents. Because of the methodological heterogeneity across studies and partially contradictory results, no conclusions could be drawn concerning the influence of factors such as psychopathology, medication type, side effects, the effectiveness of treatment, or family-related factors. Well-designed long-term studies of large patient samples and a consensus regarding definitions are therefore warranted. Such research would facilitate the design of tailored strategies to improve adherence in these patients.

Glutamatergic Agents in the Treatment of Compulsivity and Impulsivity in Child and Adolescent Psychiatry: a Systematic Review of the Literature.

OBJECTIVE: Research has implicated glutamatergic projections between the various frontal subregions in the pathogenesis of compulsivity and impulsivity. Reducing striatal glutamate release, or antagonising the action of glutamate at its receptors, may therefore represent viable treatment strategies. Several glutamatergic agents with regulatory approval for other indications are available and may be of potential benefit in the treatment of compulsivity/impulsivity in psychiatric disorders in paediatric patients. METHOD: This review was performed according to PRISMA guidelines and evaluates available scientific literature concerning the use of glutamatergic agents in these patients, in order to determine their reported effectiveness/efficacy and tolerability/safety. RESULTS: Out of a total of 1,426 publications, 21 trials examining six glutamatergic substances in patients with obsessive-compulsive disorder, autism spectrum disorders, and attention deficit/hyperactivity disorder were included. CONCLUSIONS: Trial designs as well as results were heterogeneous and thus comparability was limited. Available data support the hypothesis that glutamatergic agents are of potential value in the treatment of compulsivity/impulsivity in children and adolescents. Based on the data reviewed, memantine and N-acetylcysteine suggest the best risk-benefit profile for future trials. Riluzole should primarily be further investigated in adults. Clinical research of this nature is a key element of the TACTICS Consortium project funded by the European Union (FP7).

Outpatient antidepressant drug use in children and adolescents in Germany between 2004 and 2011.

PURPOSE: Recent studies on the utilization of antidepressant drugs in minors are scarce, methodologically limited, and do not factor in off-label use sufficiently. Beyond that, little is known about the short treatment durations that have been observed for many young antidepressant users. The present study examined antidepressant use in pediatric patients aged 0 to 17 years over time, investigated changes regarding the prescribed drugs, analyzed underlying diagnoses, and assessed the rate of off-label use. METHODS: We used claims data of roughly two million individuals to calculate annual prevalence and incidence rates of antidepressant prescriptions for the years 2004 to 2011. Analyses were stratified by age, sex, and drug type. For antidepressant users, numbers of prescriptions, frequencies of disorders/diseases, and specialties of the prescribing physicians were examined. The share of off-label prescriptions was calculated for each year. RESULTS: The prescription prevalence of antidepressants ranged between 1.7 and 2.1 per 1000 minors. The use of tricyclic antidepressants decreased from 0.9 to 0.6 prescriptions per 1000 minors, while the use of selective serotonin reuptake inhibitors increased from 0.5 to 1.1. Of the patients with an antidepressant prescription, 46.4% only received one prescription. Depression was by far the most frequent diagnosis among all antidepressant users as well as among subjects with only one prescription. In 2011, 36.3% of all prescriptions were off-label. CONCLUSIONS: The high proportion of single prescriptions, even in patients with a diagnosed depression, and the high rate of off-label use are particularly noteworthy and should be further investigated in future studies. Copyright © 2016 John Wiley & Sons, Ltd.

Extent and risks of antidepressant off-label use in children and adolescents in Germany between 2004 and 2011.

PURPOSE: So far, only little is known about antidepressant off-label use in pediatric patients. This is the first study examining the prevalence and the risks of off-label antidepressant prescriptions in minors over time in Germany and analyzing patterns regarding age, sex, drug class, and type of off-label use. METHODS: We used claims data of about two million individuals (<18 y) to calculate the share of off-label antidepressant prescriptions for the years 2004 to 2011, stratified by age, sex, and drug class. Off-label prescriptions were analyzed regarding underlying diagnoses, the prescribing doctor's specialty, and the type of off-label use. Incidence rates of adverse events were calculated for off- and on-label use, and the risk of suicidal events associated with off- or on-label use was examined in a nested case-control study. RESULTS: The prevalence of off-label prescriptions decreased from 58.0% to 40.9%. Selective serotonin reuptake inhibitors were more frequently prescribed off-label than tricyclic antidepressants (37.7% vs 17.5% in 2011). The most common type of off-label use was off-label use by age, followed by off-label use by indication, and off-label use by contraindication. Adverse events were rare with no significant differences between on- and off-label use. CONCLUSIONS: Although off-label antidepressant use in minors decreased over time, it is still common. However, this rather indicates a lack of approved drugs for the treatment of depression in this population than inappropriate medical treatment. This is supported by the fact that off-label use was not associated with a higher risk of adverse events than on-label use.

Outpatient antipsychotic drug use in children and adolescents in Germany between 2004 and 2011.

Studies from different countries showed increasing use of antipsychotics in pediatric patients. However, these studies were methodologically limited and could not assess underlying diagnoses and off-label use sufficiently. This is the first study to examine antipsychotic prescriptions in a representative sample of minors over a long period, looking at changes regarding substances and drug classes, underlying diagnoses, and the rate of off-label use. Claims data of about two million pediatric subjects were used to calculate annual prevalences and incidence rates of antipsychotic prescriptions for the years 2004-2011. Analyses were stratified by sex, age, and drug type. Numbers of prescriptions, frequencies of diseases/disorders, the prescribing physicians' specialties, and the share of off-label prescriptions were examined. During the study period, the prevalence of antipsychotic prescriptions ranged between 2.0 and 2.6 per 1000 minors. Antipsychotic prescriptions in children younger than 6 years decreased from 2.42 per 1000 subjects in 2004 to 0.48 in 2011. Among antipsychotic users, 47.0 % had only one prescription and hyperkinetic disorder was, by far, the most frequent diagnosis. The annual share of off-label prescriptions varied between 61.0 and 69.5 %. Antipsychotics were mainly prescribed to manage aggressive and impulsive behaviors in hyperkinetic disorder patients. This explains the high share of off-label prescriptions but raises concerns, since efficacy and safety of antipsychotics in this indication have not been sufficiently investigated. The decreasing antipsychotic use in younger children and the high proportion of antipsychotic users with one-time prescriptions are striking and should be further investigated in the future.

Psychometric validation of the Weiss Functional Impairment Rating Scale-Parent Report Form in children and adolescents with attention-deficit/hyperactivity disorder.

BACKGROUND: Measurement properties of the Weiss Functional Impairment Rating Scale-Parent Report Form (WFIRS-P), which assesses attention-deficit/hyperactivity disorder (ADHD)-related functional impairment in children/adolescents (6-17 years), were examined. METHODS: Data from seven randomized, controlled trials were pooled. Analyses were conducted in two random half-samples. WFIRS-P conceptual framework was evaluated using confirmatory factor analyses (CFA). Reliability was estimated using internal consistency (Cronbach's alpha) and test-retest reliability methods. Convergent validity was assessed using correlations between WFIRS-P domain scores and the ADHD-RS-IV and Clinical Global Impression-Severity (CGI-S) scales. Responsiveness was tested by comparing mean changes in WFIRS-P domain scores between responders and non-responders based on clinical criteria. RESULTS: CFA adequately confirmed the item-to-scale relationships defined in the WFIRS-P conceptual framework. Cronbach's alpha coefficient exceeded 0.7 for all domains and test-retest reliability exceeded 0.7 for all but Risky Activities. With few exceptions, WFIRS-P domains correlated significantly (p < 0.05) with ADHD-RS-IV Total, Inattention and Hyperactivity-Impulsivity scores and CGI-S at baseline and follow-up in both random half-samples. Mean changes in WFIRS-P domain scores differed significantly between responder and non-responder groups in the expected direction (p < 0.001). CONCLUSIONS: Study results support the reliability, validity and responsiveness of the WFIRS-P. Findings were replicated between two random samples, further demonstrating the robustness of results.