Limited usefulness of neurocognitive functioning indices as predictive markers for treatment response to methylphenidate or neurofeedback@home in children and adolescents with ADHD.

Introduction: Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers. Methods: Children and adolescents (n = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response. Results: For a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only. Discussion: Current findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.

Perspectives on ADHD in children and adolescents as a social construct amidst rising prevalence of diagnosis and medication use.

The diagnosis of attention-deficit hyperactivity disorder (ADHD) is based on the presence of pervasive, persistent symptoms of inattention and/or hyperactivity/impulsivity typically emerging early in life and resulting in significant functional impairment. In contrast to a worldwide epidemiological prevalence of approximately 5% in children and 2-3% in adults, there are significant variations in the prevalence of administrative ADHD diagnoses and medication use. We assert that in order to explore the underlying dynamics of this phenomenon, a thorough understanding of the construct ADHD is necessary. We contend that ADHD is not a natural entity that unfolds within an individual and can be understood independent from societal and environmental factors, but rather that ADHD as a diagnosis can better be conceptualized as a valid and pragmatically useful social construct. Decisions to diagnose and treat ADHD should follow a person-centered approach and be focused on functional impairment within a socially constructed, context-dependent and environmentally contingent model.

Memantine as treatment for compulsivity in child and adolescent psychiatry: Descriptive findings from an incompleted randomized, double-blind, placebo-controlled trial.

Background: Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) are mental disorders with a considerable overlap in terms of their defining symptoms. The glutamatergic agent memantine appears to be a promising candidate for the treatment of ASD and OCD in children and adolescents. The aim of this study was to investigate the clinical efficacy and tolerability/safety of memantine in this population. Methods: This randomized, double-blind, placebo-controlled multicenter add-on trial comprised patients aged 6 to 17; 9 years with a confirmed diagnosis of ASD and/or OCD. Participants were randomized to either memantine or placebo for 10 consecutive weeks, including an up-titration phase. Results: A total of 7 patients were included in the study. N = 4 (57.1%) participants were treated with verum (memantine) and n = 3 (42.9%) received placebo. Patients receiving memantine showed a more pronounced reduction in their CY-BOCS score, as well as greater CGI-Improvement, compared to patients receiving placebo. No serious adverse events (SAEs) were reported. Conclusions: Our findings, although based on a very small number of patients and therefore insufficient to draw clear conclusions, appear to be in line with the hypothesis that memantine is an effective, tolerable and safe agent for children and adolescents. Trial registration: EudraCT Number: 2014-003080-38, Registered 14 July 2014, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-003080-38.

Evidence-based pharmacological treatment options for ADHD in children and adolescents.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity, causing functional impairment. Its prevalence lies at approximately 5% in children and adolescents and at approximately 2.5% in adults. The disorder follows a multifactorial etiology and shows a high heritability. Patients show a high interindividual and intraindividual variability of symptoms, with executive deficits in several cognitive domains. Overall, ADHD is associated with high rates of psychiatric comorbidities, and insufficient treatment is linked to adverse long-term outcomes. Current clinical guidelines recommend an individualized multimodal treatment approach including psychoeducation, pharmacological interventions, and non-pharmacological interventions. Available medications include stimulants (methylphenidate, amphetamines) and non-stimulants (atomoxetine, guanfacine, clonidine). While available pharmacological treatment options for ADHD show relatively large effect sizes (in short-term trials) and overall good tolerability, there is still a need for improvement of current pharmacotherapeutic strategies and for the development of novel medications. This review summarizes available pharmacological treatment options for ADHD in children and adolescents, identifies current issues in research and evidence gaps, and provides an overview of ongoing efforts to develop new medications for the treatment of ADHD in children and adolescents by means of a systematic cross-sectional analysis of the clinical trials registry www.clinicaltrials.gov.

Personalized at-home neurofeedback compared to long-acting methylphenidate in children with ADHD: NEWROFEED, a European randomized noninferiority trial.

BACKGROUND: Neurofeedback is considered a promising intervention for the treatment of attention-deficit hyperactivity disorder (ADHD). NEWROFEED is a prospective, multicentre, randomized (3:2), reference drug-controlled trial in children with ADHD aged between 7 and 13 years. The main objective of NEWROFEED was to demonstrate the noninferiority of personalized at-home neurofeedback (NF) training versus methylphenidate in the treatment of children with ADHD. METHODS: The NF group (n = 111) underwent eight visits and two treatment phases of 16 to 20 at-home sessions with down-training of the theta/beta ratio (TBR) for children with high TBR and enhancing the sensorimotor rhythm (SMR) for the others. The control group (n = 67) received optimally titrated long-acting methylphenidate. The primary endpoint was the change between baseline and endpoint in the Clinician ADHD-RS-IV total score in the per-protocol population (90 NF/59 controls). TRIAL REGISTRATION: US National Institute of Health, ClinicalTrials.gov #NCT02778360. RESULTS: Our study failed to demonstrate noninferiority of NF versus methylphenidate (mean between-group difference 8.09 90% CI [8.09; 10.56]). However, both treatment groups showed significant pre-post improvements in core ADHD symptoms and in a broader range of problems. Reduction in the Clinician ADHD-RS-IV total score between baseline and final visit (D90) was 26.7% (SMD = 0.89) in the NF and 46.9% (SMD = 2.03) in the control group. NF effects increased whereas those of methylphenidate were stable between intermediate and final visit. CONCLUSIONS: Based on clinicians' reports, the effects of at-home NF were inferior to those of methylphenidate as a stand-alone treatment.

Actigraphy-Derived Sleep Profiles of Children with and without Attention-Deficit/Hyperactivity Disorder (ADHD) over Two Weeks-Comparison, Precursor Symptoms, and the Chronotype.

Although sleep problems are common in children with ADHD, their extent, preceding risk factors, and the association between neurocognitive performance and neurobiological processes in sleep and ADHD, are still largely unknown. We examined sleep variables in school-aged children with ADHD, addressing their intra-individual variability (IIV) and considering potential precursor symptoms as well as the chronotype. Additionally, in a subgroup of our sample, we investigated associations with neurobehavioral functioning (n = 44). A total of 57 children (6-12 years) with (n = 24) and without ADHD (n = 33) were recruited in one center of the large ESCAlife study to wear actigraphs for two weeks. Actigraphy-derived dependent variables, including IIV, were analyzed using linear mixed models in order to find differences between the groups. A stepwise regression model was used to investigate neuropsychological function. Overall, children with ADHD showed longer sleep onset latency (SOL), higher IIV in SOL, more movements during sleep, lower sleep efficiency, and a slightly larger sleep deficit on school days compared with free days. No group differences were observed for chronotype or sleep onset time. Sleep problems in infancy predicted later SOL and the total number of movements during sleep in children with and without ADHD. No additional effect of sleep problems, beyond ADHD symptom severity, on neuropsychological functioning was found. This study highlights the importance of screening children with ADHD for current and early childhood sleep disturbances in order to prevent long-term sleep problems and offer individualized treatments. Future studies with larger sample sizes should examine possible biological markers to improve our understanding of the underlying mechanisms.

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.

Patterns of extreme temperature-related catastrophic events in Europe including the Russian Federation: a cross-sectional analysis of the Emergency Events Database.

OBJECTIVE: To investigate reported extreme temperature-related catastrophic events and associated mortality on the European continent including the Russian Federation. DESIGN: Cross-sectional respecting Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria. SETTINGS: Data source: Emergency Events Database (EM-DAT). PARTICIPANTS: Search criteria: location-European continent including Russian Federation, time-years 1988 until 2019 (close of database 12 July 2019), catastrophic events-extreme temperatures. PRIMARY OUTCOME MEASURES: Numbers of heat waves, cold waves, severe winter conditions and associated number of deaths, overall, and per country and year, respecting STROBE criteria. RESULTS: The most frequent type of the 243 events recorded in EM-DAT were cold waves (54.7%). However, cold waves and severe winter conditions only accounted for 6460 deaths (4.5%), while heat waves were associated with 137 533 deaths (95.5%). The five most severe heat waves in 2003, 2006, 2010, 2013 and 2015 were associated with a total of 135 089 deaths. The most severe heat waves were geographically distributed over the Russian Federation (2010), as well as France, Italy, Spain and Germany, each in 2003. CONCLUSION: Although cold waves are more frequently reported in EM-DAT, heat waves are the major cause for temperature-related deaths. In order to better protect the public, it is important to address resiliency and vulnerability of populations at risk and age groups.

"Include me if you can"-reasons for low enrollment of pediatric patients in a psychopharmacological trial.

BACKGROUND: Low recruitment in clinical trials is a common and costly problem which undermines medical research. This study aimed to investigate the challenges faced in recruiting children and adolescents with obsessive-compulsive disorder and autism spectrum disorder for a randomized, double-blind, placebo-controlled clinical trial and to analyze reasons for non-participation. The trial was part of the EU FP7 project TACTICS (Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes). METHODS: Demographic data on pre-screening patients were collected systematically, including documented reasons for non-participation. Findings were grouped according to content, and descriptive statistical analyses of the data were performed. RESULTS: In total, n = 173 patients were pre-screened for potential participation in the clinical trial. Of these, only five (2.9%) were eventually enrolled. The main reasons for non-inclusion were as follows: failure to meet all inclusion criteria/meeting one or more of the exclusion criteria (n = 73; 42.2%), no interest in the trial or trials in general (n = 40; 23.1%), and not wanting changes to current therapy/medication (n = 14; 8.1%). CONCLUSIONS: The findings from this study add valuable information to the existing knowledge on reasons for low clinical trial recruitment rates in pediatric psychiatric populations. Low enrollment and high exclusion rates raise the question of whether such selective study populations are representative of clinical patient cohorts. Consequently, the generalizability of the results of such trials may be limited. The present findings will be useful in the development of improved recruitment strategies and may guide future research in establishing the measurement of representativeness to ensure enhanced external validity in psychopharmacological clinical trials in pediatric populations. TRIAL REGISTRATION: EudraCT 2014-003080-38 . Registered on 14 July 2014.

Quantitative retrospective natural history modeling for orphan drug development.

The natural history of most rare diseases is incompletely understood and usually relies on studies with low level of evidence. Consistent with the goals for future research of rare disease research set by the International Rare Diseases Research Consortium in 2017, the purpose of this paper is to review the recently developed method of quantitative retrospective natural history modeling (QUARNAM) and to illustrate its usefulness through didactically selected analyses examples in an overall population of 849 patients worldwide with seven (ultra-) rare neurogenetic disorders. A quantitative understanding of the natural history of the disease is fundamental for the development of specific interventions and counseling afflicted families. QUARNAM has a similar relationship to a published case study as a meta-analysis has to an individual published study. QUARNAM relies on sophisticated statistical analyses of published case reports focusing on four research questions: How long does it take to make the diagnosis? How long do patients live? Which factors predict disease severity (eg, genotypes, signs/symptoms, biomarkers)? Where can patients be recruited for studies? Useful statistical techniques include Kaplan-Meier estimates, cluster analysis, regression techniques, binary decisions trees, word clouds, and geographic mapping. In comparison to other natural history study methods (prospective studies or retrospective studies such as chart reviews), QUARNAM can provide fast information on hard clinical endpoints (ie, survival, diagnostic delay) with a lower effort. The choice of method for a particular drug development program may be driven by the research question and may encompass combinatory approaches.

FDA orphan drug designations for lysosomal storage disorders - a cross-sectional analysis.

PURPOSE: To provide a quantitative clinical-regulatory insight into the status of FDA orphan drug designations for compounds intended to treat lysosomal storage disorders (LSDs). METHODS: Assessment of the drug pipeline through analysis of the FDA database for orphan drug designations with descriptive and comparative statistics. RESULTS: Between 1983 and 2019, 124 orphan drug designations were granted by the FDA for compounds intended to treat 28 lysosomal storage diseases. Orphan drug designations focused on Gaucher disease (N = 16), Pompe disease (N = 16), Fabry disease (N = 10), MPS II (N = 10), MPS I (N = 9), and MPS IIIA (N = 9), and included enzyme replacement therapies, gene therapies, and small molecules, and others. Twenty-three orphan drugs were approved for the treatment of 11 LSDs. Gaucher disease (N = 6), cystinosis (N = 5), Pompe disease (N = 3), and Fabry disease (N = 2) had multiple approvals, CLN2, LAL-D, MPS I, II, IVA, VI, and VII one approval each. This is an increase of nine more approved drugs and four more treatable LSDs (CLN2, MPS VII, LAL-D, and MPS IVA) since 2013. Mean time between orphan drug designation and FDA approval was 89.7 SD 55.00 (range 8-203, N = 23) months. CONCLUSIONS: The drug development pipeline for LSDs is growing and evolving, with increased focus on diverse small-molecule targets and gene therapy. CLN2 was the first and only LSD with an approved therapy directly targeted to the brain. Newly approved products included "me-too"-enzymes and innovative compounds such as the first pharmacological chaperone for the treatment of Fabry disease.

Disease awareness or subtle product placement? Orphan diseases featured in the television series "House, M.D." - a cross-sectional analysis.

BACKGROUND: Approximately 7% of the general population is affected by an orphan disease, which, in the United States, is defined as affecting fewer than 1 in 1500 people. Disease awareness is often low and time-to-diagnosis delayed. Different legislations worldwide have created incentives for pharmaceutical companies to develop drugs for orphan diseases. A journalistic article in Bloomberg Businessweek has claimed that pharmaceutical companies have tried marketing orphan drugs by placing a specific disease into the popular television series "House, M.D." which features diagnostic journeys and was produced between 2004 and 2012. This study aimed to describe the presentation of orphan diseases in the television series "House, M.D.", to test in an exploratory fashion the hypothesis that treatable orphan conditions are overrepresented in "House, M.D." and to discuss whether such marketing practices may or may not be ethical. METHODS: A list of all medical cases depicted in the television series "House, M.D." was obtained and classified as orphan or non-orphan according to the Orphanet database. The ratios of orphan diseases among all diseases, such with an orphan drug designation and such with an orphan drug approval by the FDA were then compared with conservative approximations of real world conditions (chi-squared tests for equality of proportions). STROBE criteria were respected. RESULTS: Out of a total of n = 181 different medical diagnoses, n = 42 (23.2%) were orphan diseases. The difference in percentages in between "House, M.D." and reality was not statistically significant for orphan diseases overall (p = 0.96), yet was statistically significantly higher for both orphan diseases with one or more orphan drug designations (p = 0.0192) and such with one or more approved orphan drugs (p < 0.0001). CONCLUSIONS: Orphan diseases with a designated and/or approved orphan drug were overrepresented in the television series "House, M.D." with statistical significance while orphan diseases overall were not. This may be explained by (so far) undocumented efforts of pharmaceutical companies to place their orphan drugs in the television series, as described in the article in Bloomberg Businessweek. Further research is needed into marketing practices in popular and emerging media formats.

Disasters in Germany and France: An Analysis of the Emergency Events Database From a Pediatric Perspective.

OBJECTIVE: The objective of this study was to conduct comprehensive analyses of disaster patterns for Germany and France from a pediatric perspective. METHODS: An analysis of the Emergency Events Database (EM-DAT), epidemiological database with standard methods of descriptive and comparative statistics respecting the strengthening the reporting of observational studies in epidemiology (STROBE) criteria, was performed. RESULTS: Between 2006 and 2016, there were 41 and 42 disasters in Germany and France claiming 259 and 4973 lives, respectively. Ages of afflicted individuals were not specified in EM-DAT. In Germany, most events were storms (37%), extreme temperatures (17%), floods (17%), and transport accidents (17%). In France, most events were storms (45%), extreme temperatures (17%), floods (19%), and transport accidents (14%). In Germany, most lives (96) were lost in transport accidents. In France, most casualties were due to the heat waves of 2006 and 2015 (1388 and 3275). Reported event types in Germany and France were similar, but heat waves struck France more significantly than Germany. CONCLUSIONS: Pediatric data are not explicitly captured in EM-DAT, but reported disaster patterns suggest that exposures to heat and cold, storms, trauma, chemicals, water, and infectious agents are possible mechanisms of injury. Age-stratified disaster data are needed to enable a timely, transparent, coordinated, and sustained data-driven approach to pediatric disaster resilience.

"Drugs Don't Work in Patients Who Don't Take Them".

The more recent term "adherence" is now taking the place of the earlier notion of "compliance," as it emphasizes the physician-patient partnership. To date, however, it has not been clearly defined. There are many limitations to measuring adherence, and presently no standard methods have been established. Even in clinical trials throughout medicine, the reported rates for adherence range only between 43 % and 78 %. Particularly medication adherence is highly relevant to the treatment of mentally ill adolescents, as they make up a population especially vulnerable to nonadherence - and high rates thereof have been reported. Factors influencing adherence are poorly understood and researched, especially in adolescents with mental illness. Physicians can currently rely only on concepts from other populations and expert recommendations. Concepts for children or adults should not directly be transferred to adolescent patients. Results from the current "SEMA" study should contribute to guiding future research in the development of interventions to improve medication adherence, in particular for this juvenile population.

Screening for ADHD-Related Symptoms in Preschoolers Should Be Considered-Results From a Representative Sample of 5-Year-Olds From a German Metropolitan Region.

Background: Early assessment and intervention are crucial to alleviate symptoms and prevent long-term negative outcomes in children suffering from Attention-deficit/hyperactivity disorder (ADHD). In Germany, at present, no standardized screening for ADHD is routinely administered. This study aims to evaluate a potential screening measure in a study population that is representative for a primary school entrance exam population in a German metropolitan region. Methods: Based on various socio-demographic variables, a sample of n = 500 5-year-old children (58% boys, 42% girls), representative of a primary school entrance exam population from a German metropolitan region, was selected. Their parents completed a written survey consisting of the CBCL and a brief screening tool for ADHD symptomatology based on the DISYPS-II questionnaire. Demographic data were also collected. Results: The subscale "Attention problems" of the CBCL/4-18 showed results in the clinical range for n = 10 (2%) participants. The ADHD screening identified n = 23 (4.6%) participants as suspect of having ADHD with a statistically significant gender difference (n = 17 boys vs. n = 6 girls, p = 0.03). In n = 5 (1%) participants, all boys, both CBCL/4-18 and the ADHD screening were indicative of ADHD. Conclusions: Results indicate that screening for ADHD in this population may be both feasible and reasonable given the high prevalence and chronic nature of this disorder and the benefit of an early initiation of treatment. Results match previously reported figures for prevalence of ADHD-related symptoms and gender differences in preschool and older pediatric populations and thus do not support the hypothesis that the prevalence of ADHD in a metropolitan region is significantly higher than in other regions.

Effects of long-term methylphenidate use on growth and blood pressure: results of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS).

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

"When I Stop My Medication, Everything Goes Wrong": Content Analysis of Interviews with Adolescent Patients Treated with Psychotropic Medication.

OBJECTIVES: Medication nonadherence constitutes a major problem in adolescent psychiatry. Previous studies have identified various factors associated with nonadherent behavior. The aim of this study is to explore adolescents' health beliefs and subjective perceptions relating to psychotropic medication, and to statistically link these to reported medication adherence. METHODS: The findings presented in this study are part of the multicenter SEMA study (Subjective Experience and Medication Adherence in Adolescents with Psychiatric Disorders). Patients 12-18 years of age were included, who had been treated with a psychotropic medication for at least 2 weeks. The validated MARS (Medication Adherence Rating Scale) and the QATT (Questionnaire on Attitudes Toward Treatment) were used to measure adherence, and a qualitative semi-structured interview was conducted to examine patients' subjective experiences and perceptions. A conventional content analysis was conducted, and Fisher's exact tests were performed to analyze group differences between completely adherent and not completely adherent patients. RESULTS: A total of 64 patients were included in the study. 40.6% (n = 26) were classified as not completely adherent. Distribution patterns of answers to 7 out of 64 questions showed statistically significant group differences between completely and not completely adherent patients. Patients with lower adherence reported the following: feeling worse after taking medication; a lower sense of self-efficacy concerning the improvement of their symptoms; a less trustful physician-patient relationship; a worsened attitude toward medication after experiencing adverse events/"side effects"; less support from their relatives; and fewer individuals in their family who were fully informed about their condition. CONCLUSIONS: To our knowledge, this is the first interview-based study to investigate subjective experiences and health beliefs of adolescents with psychiatric disorders and to correlate these findings with rates of medication adherence. The study results will be useful for the development of tools and approaches to increase medication adherence, for example, psychoeducation programs and personalized treatment concepts.

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.