Bright Light Therapy as Add-On to Inpatient Treatment in Youth With Moderate to Severe Depression: A Randomized Clinical Trial.

Importance: Major depressive disorder is one of the most common mental disorders among adolescents, entailing severe, long-term psychosocial impairment and a high risk of chronicity. In view of the large number of patients requiring treatment, along with insufficient treatment responses with small effect sizes, innovative adjunctive treatment strategies are urgently needed. Objective: To investigate whether the effect of adolescent psychiatric inpatient treatment as usual for major depressive disorder can be enhanced by simultaneous use of morning bright light therapy. Design, Setting, and Participants: This was a double-blind, placebo-controlled randomized parallel-group trial with enrollment between March 2018 and November 2020 and follow-up completed in May 2021. The study took place among inpatients at 4 university hospitals for child and adolescent psychiatry across Germany. Of 248 eligible youth aged 12 to 18 years fulfilling ICD-10 criteria for major depressive disorder, 227 were randomized to bright light therapy (n = 116) or placebo red light (n = 111); 151 participants completed the study. Interventions: Up to 20 sessions of either morning bright light therapy with an intensity of 10 000 lux or placebo red light (100 lux) in addition to multimodal inpatient treatment as usual over 4 weeks. Main Outcomes and Measures: The primary outcome was the change in Beck Depression Inventory-II (BDI-II) score from baseline to posttreatment in the intention-to-treat sample. Results: Among the 224 patients included in the intention-to-treat analyses (192 girls and 32 boys; mean [SD] age, 15.5 [1.4] years), the mean (SD) BDI-II score at baseline was 37.3 (8.7). BDI-II scores were significantly reduced after 4 weeks (postassessment) by a mean of -7.5 (95% CI, -9.0 to -6.0; Hedges g = 0.71). Bright light therapy had no impact on this change (no significant group × time effect). Loss to follow-up was 31% (n = 69) at 16 weeks and 49% (n = 110) at 28 weeks. There were 10 serious adverse events throughout the whole trial, which were not considered related to study treatment. Conclusions and Relevance: The findings in this study did not indicate superiority of bright light therapy over placebo red light therapy in a large sample of adolescent inpatients with moderate or severe major depressive disorder. Both groups benefited equally from treatment as usual, showing relevant symptom reduction. Trial Registration: German Clinical Trials Register: DRKS00013188.

[How can we ensure the future care for children and adolescents with mental disorders?] / Wie sichern wir in Zukunft die Versorgung von Kindern und Jugendlichen mit psychischen Erkrankungen?

The interdisciplinary care of children and adolescents with mental disorders requires services from various German codes of social law and-within the medical care system-enclosing inpatient and outpatient services. The increasing demand, the increase in severity of disorders, and the general shortage of staff in social services put pressure on the structures of the interdisciplinary service networks resulting in long waiting periods, long distances, and regionally insufficient care. The medical field of child and adolescent psychiatry and psychotherapy (CAPP) plays the central and coordinating role within the cooperative care for children and adolescents with mental disorders. The CAPP is in clear need of reforms; however, these are markedly different from the reform needs of the German somatic medical care system and differ substantially from those of the (adult) psychiatry, psychotherapy, and psychosomatics disciplines. This discussion paper describes the reform requirements, the specifics of the CAPP structures, and suggestions to overcome sectors of service provision, enhance networking, intensify telemedicine, and develop evidence-based prevention and early recognition of child mental disorders.

[Support for families with a mentally ill parent : Which forms of help do mentally ill parents utilize and which would they like to have?] / Unterstützung für Familien mit einem psychisch erkrankten Elternteil : Welche Hilfen nehmen psychisch erkrankte Eltern in Anspruch und welche wünschen sie sich?

BACKGROUND: In Germany different offers of social support are available for families that are provided by different sectors, e.g., the youth welfare and the healthcare systems. OBJECTIVE: Documentation of the utilized help, child-related factors that are associated with the utilization and the parental desires for support. MATERIAL AND METHODS: Survey of 160 parents undergoing (partial) inpatient treatment in psychiatric hospitals via an oral interview using standardized and semi-standardized instruments. RESULTS: The results show that nonprofessional help by family and friends as well as support offers provided by the healthcare system are used most frequently. Families that perceived their children as more burdened receive more help than families with children judged as being less burdened. There are regional differences especially in the utilization of high-threshold help by the healthcare system. DISCUSSION: Support offers seem to reach families with mental illnesses, especially those that are particularly burdened; however, there are regional differences regarding the utilization of support as well as the wishes for specific support offers.

Therapeutic Drug Monitoring in Children and Adolescents: Findings on Fluoxetine from the TDM-VIGIL Trial.

Fluoxetine is the recommended first-line antidepressant in many therapeutic guidelines for children and adolescents. However, little is known about the relationships between drug dose and serum level as well as the therapeutic serum reference range in this age group. Within a large naturalistic observational prospective multicenter clinical trial ("TDM-VIGIL"), a transdiagnostic sample of children and adolescents (n = 138; mean age, 15; range, 7-18 years; 24.6% males) was treated with fluoxetine (10-40 mg/day). Analyses of both the last timepoint and all timepoints (n = 292 observations), utilizing (multiple) linear regressions, linear mixed-effect models, and cumulative link (mixed) models, were used to test the associations between dose, serum concentration, outcome, and potential predictors. The receiver operating curve and first to third interquartile methods, respectively, were used to examine concentration cutoff and reference values for responders. A strong positive relationship was found between dose and serum concentration of fluoxetine and its metabolite. Higher body weight was associated with lower serum concentrations, and female sex was associated with lower therapeutic response. The preliminary reference ranges for the active moiety (fluoxetine+norfluoxetine) were 208-328 ng/mL (transdiagnostically) and 201.5-306 ng/mL (depression). Most patients showed marked (45.6%) or minimal (43.5%) improvements and reported no adverse effects (64.9%). This study demonstrated a clear linear dose-serum level relationship for fluoxetine in youth, with the identified reference range being within that established for adults.

Electroconvulsive therapy in children and adolescents in Europe-a systematic review of the literature complemented by expert information and guideline recommendations.

The first documented pediatric use of Electroconvulsive therapy (ECT) occurred in Europe in 1941. Since then, predominantly successful treatments and reasonable side effects have been reported in severely ill minors. Nevertheless, a shy reluctance determines the controversy about ECT in young patients. This study describes the use of ECT in children and adolescents in Europe. We systematically searched the literature concerning the practice of ECT in minors in all 53 European countries. In addition, we surveyed European experts about national practices and compared guidelines for ECT in minors. The search yielded 79 publications from 18 European countries, mainly from Western Europe, Israel, and Turkey. National data were available from eight countries. These showed an interestingly high relationship between the number of minors treated with ECT and the general use of ECT. No persistent deficits or deaths were reported. On the other hand, no randomized clinical trial was found, and many publications lacked relevant information. Accordingly, the appraisal of the evidence in the guidelines varies considerably. Experts from 13 European countries consistently reported infrequent and unsystematic use of ECT in minors. ECT has been used successfully in minors in Europe with reasonable complications and side effects. Adverse effects on the developing brain, as often suspected, have not been scientifically supported in eight decades. Nevertheless, the use of ECT in Europe is sparse and dependent on accidental circumstances. High-quality evidence is needed, as well as improved knowledge and training of child and adolescent psychiatrists.

[The landscape of child and adolescent psychiatry and psychotherapy in Germany: structures, challenges, and developments]. / Die Versorgungslandschaft der Kinder- und Jugendpsychiatrie und -psychotherapie in Deutschland: Strukturen, Herausforderungen und Entwicklungen.

For children and adolescents in need of psychiatric and psychotherapeutic care, outpatient, day patient, and inpatient facilities are provided. A new development is called "inpatient equivalent treatment" that consists of home visits by a multiprofessional team. This paper depicts the landscape of Child and Adolescent Psychiatry (CAP) Services, covering its historical development and the structural, care policy, and financing backgrounds. Until 2014, there was free choice of private practice locations in the outpatient sector, leaving rural areas and marginalized neighborhoods partially undersupplied until today.The number of beds in the hospital sector decreased significantly between 1991 and 2004. It later rose again in favor of improved regional access and smaller units, with an additional 50% of day patient places. Inpatient equivalent treatments are equally effective, but not yet established nationwide; only a few innovative models have been negotiated. Regional networks of all social support systems, aiming for child psychiatric supply networks, are limited due to the pillarization of the social system. In conclusion, an imperative cooperation between all services of the Social Security Code and enabling true cross-sectoral services would benefit CAP patients.

[COVID-19 and Psychiatric Disorders in Minors: Changes in Inpatient Treatment According to Hospital Statistics]. / COVID-19 und psychische Störungen bei Minderjährigen: Veränderungen der Behandlungen nach der Krankenhausstatistik.

COVID-19 and Psychiatric Disorders in Minors: Changes in Inpatient Treatment According to Hospital Statistics Abstract: Increased rates of psychiatric disorders and psychiatric emergencies in children and adolescents stemming from the COVID-19 pandemic have been reported, with more children and adolescents suffering from internalizing disorders. This study analyzes whether the increased rates led to increased rates of inpatient treatment in child and adolescent psychiatric and pediatric hospitals in Germany as well as a change in diagnoses of the treated patients. We analyzed routine hospital data ("InEK" data, § 21 KHG data files) from a prepandemic (2019) and a pandemic (2021) half-year regarding changes in the number of cases, diagnoses, and length of stay (LoS) in child and adolescent psychiatry and pediatrics. We also investigated the development of psychiatric emergencies in minors. We found an increase in internalizing problems (depression, anorexia nervosa, trauma-related disorders) and a decrease in externalizing problems among the admitted psychiatric inpatients. Further, we observed a halving of cases treated for alcohol intoxication. However, we discovered no change for the frequency of psychiatric emergency treatments nationwide. A more detailed analysis revealed that, in areas with a low number of child and adolescent psychiatry inpatient beds, emergency care was prioritized and LoS decreased, whereas in areas with a fair bed-to-inhabitant ratio among minors, there was a trend toward increased LoS, also in pediatric departments. We recommend continued monitoring of inpatient care after the pandemic, with special attention paid to underprivileged children and adolescents such as those with externalizing problems.

LessStress - how to reduce stress in school: evaluation of a universal stress prevention in schools: study protocol of a cluster-randomised controlled trial.

BACKGROUND: Chronic stress is detrimental to health, and children and young people have had to cope with significantly more stress since the start of the COVID-19 pandemic. In particular, stress at school and in relation to learning is a major problem in this age group. Studies in Germany have indicated that the pandemic has led to a reduced quality of life (QoL) and an increased risk for psychiatric disorders in children and adolescents. Schools are an ideal setting for interventions against stress, which is one of the strongest predictors for the development of psychosocial problems. The present study seeks to address stress by means of a short prevention training programme in schools, including emotion regulation, mindfulness, and self-compassion. In addition to information material for self-study, students should have the opportunity to actively deal with the topic of stress and develop coping strategies within a short space of time. In contrast to very long stress reduction programmes that often last several weeks, the programme is delivered in just 90 min. METHODS: The effectiveness of the short and economical prevention programme LessStress will be examined in a cluster-randomised controlled trial (RCT) encompassing 1894 students. At several measurement time points, students from two groups (intervention and control) will be asked about their subjectively perceived stress levels, among other aspects. Due to the clustered nature of the data, mainly multilevel analyses will be performed. DISCUSSION: In Germany, there are no nationwide universal prevention programmes for students against stress in schools, and this gap has become more evident since the outbreak of the pandemic. Universal stress prevention in schools may be a starting point to promote resilience. By dealing with stress in a healthy way, mental health can be strengthened and maintained. Moreover, to reach at-risk students at an early stage, we advocate for a stronger networking between child psychiatry and schools. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00025721 . Registered on November 4, 2021.

Validation of a new emotion regulation self-report questionnaire for children.

OBJECTIVE: To examine and validate the self-report Questionnaire on the Regulation of Unpleasant Moods in Children (FRUST), which is a modified and shortened version of the Questionnaire for the Assessment of Emotion Regulation in Children and Adolescents (FEEL-KJ). METHODS: The data comprised child and parent ratings of a community-screened sample with differing levels of affective dysregulation (AD) (N = 391, age: M = 10.64, SD = 1.33, 56% male). We conducted latent factor analyses to establish a factor structure. Subsequently, we assessed measurement invariance (MI) regarding age, gender, and AD level and evaluated the internal consistencies of the scales. Finally, we examined the convergent and divergent validity of the instrument by calculating differential correlations between the emotion regulation strategy (ERS) scales and self- and parent-report measures of psychopathology. RESULTS: A four-factor model, with one factor representing Dysfunctional Strategies and the three factors Distraction, Problem-Solving and Social Support representing functional strategies provided the best fit to our data and was straightforward to interpret. We found strong MI for age and gender and weak MI for AD level. Differential correlations with child and parent ratings of measures of psychopathology supported the construct validity of the factors. CONCLUSIONS: We established a reliable and valid self-report measure for the assessment of ERS in children. Due to the reduced number of items and the inclusion of highly specific regulatory behaviors, the FRUST might be a valuable contribution to the assessment of ER strategies for diagnostic, therapeutic, and research purposes.

Clock Genes Profiles as Diagnostic Tool in (Childhood) ADHD-A Pilot Study.

Attention deficit hyperactivity disorder (ADHD) is a very common disorder in children and adults. A connection with sleep disorders, and above all, disorders of the circadian rhythm are the subject of research and debate. The circadian system can be represented on different levels. There have been a variety of studies examining 24-h rhythms at the behavioral and endocrine level. At the molecular level, these rhythms are based on a series of feedback loops of core clock genes and proteins. In this paper, we compared the circadian rhythms at the behavioral, endocrine, and molecular levels between children with ADHD and age- and BMI-matched controls, complementing the previous data in adults. In a minimally invasive setting, sleep was assessed via a questionnaire, actigraphy was used to determine the motor activity and light exposure, saliva samples were taken to assess the 24-h profiles of cortisol and melatonin, and buccal mucosa swaps were taken to assess the expression of the clock genes BMAL1 and PER2. We found significant group differences in sleep onset and sleep duration, cortisol secretion profiles, and in the expression of both clock genes. Our data suggest that the analysis of circadian molecular rhythms may provide a new approach for diagnosing ADHD in children and adults.

Attitudes toward innovative mental health treatment approaches in Germany: E-mental health and home treatment.

E-mental health and home treatment are treatment approaches that have proven to be effective, but are only slowly implemented in the German health care system. This paper explores the attitudes toward these innovative treatment approaches. Data was collected in two large, non-clinical samples representative of the German population in spring 2020 (N = 2,503) and winter 2020/2021 (N = 2,519). Statistical associations between variables were examined using two-tailed tests. Binary and multinomial logistic regressions were performed to predict attitudes toward online-based treatment concepts and home treatment approaches. Only few (<20%) people preferred online-based treatment approaches, while a larger proportion (~50%) could imagine being treated at home. Overall, younger subjects were more open to online-therapy approaches, while people with lower education preferred more often a traditional therapy setting. Acceptance of online-therapy did not raise significantly during the first months of the COVID-19 pandemic. When different online-based treatment options were available, the probability of accepting home treatment significantly increased with increasing levels of therapeutic support. Further promotion of acceptance for online-therapy and home treatment seems to be necessary. In the future, more information on innovative treatment approaches should be actively provided.

Electroconvulsive Therapy in Children and Adolescents in Germany-A Case Series From 3 University Hospitals.

OBJECTIVE: Electroconvulsive therapy (ECT) is a well-established, safe, and efficacious treatment for severe psychiatric disorders. In children and adolescents, it is used much less frequently than in adults, likely because of a lack of knowledge. METHODS: We retrospectively analyzed all patients aged 12 to 17 years who completed a course of ECT at 3 psychiatric university hospitals in Germany between 2010 and 2020. Clinical Global Impression Severity (CGI-S) scores were assessed based on electronic medical records. Changes in CGI-S scores were assessed using a paired samples t test. Predictors for response and remission were assessed using binomial logistic regression. RESULTS: We included 32 patients. The CGI-S scores improved significantly from before to after ECT treatment (6.9 vs 3.9, t = 10.0, P < 0.01). A total of 40.6% of patients responded (CGI ≤ 3) and 21.9% remitted (CGI ≤ 2). The number of ineffective medication trials in the 6 months before ECT treatment was significantly associated with response (odds ratio, 0.54; P = 0.028) and remission (odds ratio, 0.31; P = 0.048). Five patients reported subjective cognitive adverse effects, 2 patients exhibited a prolonged seizure, 1 patient reported headaches, and 1 patient experienced a mild allergic reaction after anesthesia with etomidate. A total of 65.6% of patients experienced no adverse effects at all. CONCLUSIONS: This retrospective analysis found ECT to be effective and safe in children and adolescents irrespective of their main diagnosis. The reported data point to the importance of an early use of ECT for severe psychiatric diseases in child and adolescent psychiatry.

Possible Effects of Bright Light Therapy on Electroencephalogram-Vigilance in the Treatment of Depression in Adolescents: A Pilot Study.

Background: Chronotherapeutic treatments for depression, such as bright light therapy (BLT), are non-invasive and produce almost no side effects. However, study evidence for reliable neurobiological changes associated with treatment response is still rare. Several studies using EEG-vigilance indicate higher arousal and a later decline during resting state in adult depressive patients compared to healthy controls. To our knowledge, there are no study reports on EEG-vigilance in depressive youth to date. Methods: A total of 11 adolescents with depression receiving BLT were compared to 11 age and gender-matched patients with depression receiving treatment as usual (TAU). The BLT was administered in the morning for 2 weeks on five consecutive days per week. The depressive symptomatology was assessed using the Beck Depression Inventory (BDI-II) and the resting state electroencephalogram (EEG) of 20 min was recorded. EEG and BDI-II were assessed before and after 10 days of treatment. Vigilance level and vigilance decline were estimated using the VIGALL toolbox. Results: Brain arousal increased after 10 days of bright light therapy in adolescents with depression. Severe depressive symptoms were associated with higher brain arousal levels; the BDI-II sum score correlated negatively with the amount of drowsiness. Limitations: The sample size was small and participants' brain arousal at baseline was not matched and differed between BLT and TAU groups. Conclusion: The BLT might have an additional effect on brain arousal. EEG-vigilance seems to be a reliable and valid marker for neurobiological changes that are probably associated with depression and its treatment and, therefore, might be of clinical relevance.

[Parental Stress: Psychometric Evaluation of the German Version of the Parental Stress Scale in the General Population]. / Stress durch Elternschaft: Psychometrische Evaluation der deutschen Version der Parental Stress Scale in der Allgemeinbevölkerung.

Parental stress has negative impact on parents and their children. Parental stress may be of special interest for family and child well-being due to Covid-19 pandemic. A reliable and valid assessment of parental stress would be beneficial both in research and clinical practice. The Parental Stress Scale (PSS) is internationally well established as an economic and psychometric valid assessment. It consists of 18 items. The study evaluated the factor structure of the German version of the PSS in a general population (n=386 parents with children<16 years) for the first time. The sample was part of a representative sample (n=2519). The confirmatory factor analysis did not confirm internationally previously reported models. Eliminating one item, the explorative factor analysis suggested a two factor structure with the dimensions "lack of confident" and "worries and strain". Both subscales showed a good internal consistence (McDonalds ω≥0,87). We observed correlations of the PSS-17 items with family dysfunction and elevated scores for depressive or anxiety symptoms, but not with sociodemographic factors. One conclusion is that the multidimensional construct of parental stress maybe is not comprehensively represented by the PSS. For the use in clinical practice and research this has to be taken into account. Albeit, the German version of the PSS is an economic, reliable and valid assessment.

Therapeutic drug monitoring of sertraline in children and adolescents: A naturalistic study with insights into the clinical response and treatment of obsessive-compulsive disorder.

BACKGROUND: Sertraline is a selective serotonin reuptake inhibitor with specific indications in child and adolescent psychiatry. Notwithstanding its frequent use and clinical benefits, the relationship between pharmacokinetics, pharmacodynamics, efficacy, and tolerability of sertraline across indications, particularly in non-adult patients, is not fully understood. METHOD: This naturalistic therapeutic drug monitoring (TDM) study was conducted in a transdiagnostic sample of children and adolescents treated with sertraline (n = 78; mean age, 14.22 ± 2.39; range, 7-18 years) within the prospective multicenter "TDM-VIGIL" project. Associations between dose, serum concentration, and medication-specific therapeutic and side effects based on the Clinical Global Impression scale were examined. Tolerability was measured qualitatively with the 56-item Pediatric Adverse Event Rating Scale. RESULTS: A strong linear positive dose-serum concentration relationship (with dose explaining 45% of the variance in concentration) and significant effects of weight and co-medication were found. Neither dose nor serum concentration were associated with side effects. An overall mild-to-moderate tolerability profile of sertraline was observed. In contrast with the transdiagnostic analysis that did not indicate an effect of concentration, when split into depression (MDD) and obsessive-compulsive disorder (OCD) diagnoses, the probability of clinical improvement significantly increased as both dose and concentration increased for OCD, but not for MDD. CONCLUSIONS: This TDM-flexible-dose study revealed a significant diagnosis-specific effect between sertraline serum concentration and clinical efficacy for pediatric OCD. While TDM already guides clinical decision-making regarding compliance, dose calibration, and drug-drug interactions, combining TDM with other methods, such as pharmacogenetics, may facilitate a personalized medicine approach in psychiatry.

Serious Adverse Drug Reactions in Children and Adolescents Treated On- and Off-Label with Antidepressants and Antipsychotics in Clinical Practice.

INTRODUCTION: Despite the growing evidence base for psychotropic drug treatment in pediatric patients, knowledge about the benefit-risk ratio in clinical practice remains limited. The 'Therapeutic Drug Monitoring (TDM)-VIGIL' study aimed to evaluate serious adverse drug reactions (ADRs) in children and adolescents treated with antidepressants and/or antipsychotics in approved ('on-label'), and off-label use in clinical practice. METHODS: Psychiatric pediatric patients aged 6-18 years treated with antidepressants and/or antipsychotics either on-label or off-label were prospectively followed between October 2014 and December 2018 within a multicenter trial. Follow-up included standardized assessments of response, serious ADRs and therapeutic drug monitoring. RESULTS: 710 youth (age=14.6±2.2 years, female=66.6%) were observed for 5.5 months on average; 76.3% received antidepressants, 47.5% antipsychotics, and 25.2% both. Altogether, 55.2% of the treatment episodes with antidepressants and 80.7% with antipsychotics were off-label. Serious ADRs occurred in 8.3% (95%CI=6.4-10.6%) of patients, mainly being psychiatric adverse reactions (77.4%), predominantly suicidal ideation and behavior. The risk of serious ADRs was not significantly different between patients using psychotropics off-label and on-label (antidepressants: 8.1% vs. 11.3%, p=0.16; antipsychotics: 8.7% vs 7.5%, p=0.67). Serious ADRs occurred in 16.6% of patients who were suicidal at enrollment versus 5.6% of patients who were not suicidal (relative risk 3.0, 95%CI=1.9-4.9). CONCLUSION: Off-label use of antidepressants and antipsychotics in youth was not a risk factor for the occurrence of serious ADRs in a closely monitored clinical setting. Results from large naturalistic trials like ours can contribute to bridging the gap between knowledge from randomized controlled trials and real-world clinical settings.