Premorbid body weight predicts weight loss in both anorexia nervosa and atypical anorexia nervosa: Further support for a single underlying disorder.

OBJECTIVE: For adolescents, DSM-5 differentiates anorexia nervosa (AN) and atypical AN with the 5th BMI-centile-for-age. We hypothesized that the diagnostic weight cut-off yields (i) lower weight loss in atypical AN and (ii) discrepant premorbid BMI distributions between the two disorders. Prior studies demonstrate that premorbid BMI predicts admission BMI and weight loss in patients with AN. We explore these relationships in atypical AN. METHOD: Based on admission BMI-centile < or ≥5th, participants included 411 female adolescent inpatients with AN and 49 with atypical AN from our registry study. Regression analysis and t-tests statistically addressed our hypotheses and exploratory correlation analyses compared interrelationships between weight loss, admission BMI, and premorbid BMI in both disorders. RESULTS: Weight loss in atypical AN was 5.6 kg lower than in AN upon adjustment for admission age, admission height, premorbid weight and duration of illness. Premorbid BMI-standard deviation scores differed by almost one between both disorders. Premorbid BMI and weight loss were strongly correlated in both AN and atypical AN. DISCUSSION: Whereas the weight cut-off induces discrepancies in premorbid weight and adjusted weight loss, AN and atypical AN overall share strong weight-specific interrelationships that merit etiological consideration. Epidemiological and genetic associations between AN and low body weight may reflect a skewed premorbid BMI distribution. In combination with prior findings for similar psychological and medical characteristics in AN and atypical AN, our findings support a homogenous illness conceptualization. We propose that diagnostic subcategorization based on premorbid BMI, rather than admission BMI, may improve clinical validity. PUBLIC SIGNIFICANCE: Because body weights of patients with AN must drop below the 5th BMI-centile per DSM-5, they will inherently require greater weight loss than their counterparts with atypical AN of the same sex, age, height and premorbid weight. Indeed, patients with atypical AN had a 5.6 kg lower weight loss after controlling for these variables. In comparison to the reference population, we found a lower and higher mean premorbid weight in patients with AN and atypical AN, respectively. Considering previous psychological and medical comparisons showing little differences between AN and atypical AN, we view a single disorder as the most parsimonious explanation. Etiological models need to particularly account for the strong relationship between weight loss and premorbid body weight.

The impact of the COVID-19 pandemic on administrative eating disorder prevalence in the outpatient sector and on severity of anorexia nervosa.

The COVID-19 pandemic appears to have had a considerable impact on the mental health of children and adolescents, particularly regarding eating disorders. However, it remains unclear whether the pandemic affected only the frequency or also the severity of eating disorders. We examined potential pandemic-related changes in the administrative prevalence of eating disorders in the outpatient sector compared with other mental disorders using German statutory health insurance data for the age group 10 to 16 years. We also examined disorder severity of anorexia nervosa using data from the multicenter German Registry of Children and Adolescents with Anorexia Nervosa in the same age group. Our results showed a marked increase in the administrative prevalence of eating disorders (based on documented diagnoses) in the outpatient sector among girls but not among boys. A similar pattern was found for internalizing disorders, whereas the administrative prevalences of externalizing disorders decreased. Regarding the severity of anorexia nervosa among inpatients, we found no pandemic-related changes in body mass index standard deviation score at admission, body weight loss before admission, psychiatric comorbidities and psychopharmacological medication. Given the administrative prevalence increase in the outpatient sector, the lack of impact of the pandemic on the inpatient sector may also be partly due to a shift in healthcare utilization towards outpatient services during the pandemic. Thus, the higher number of children and adolescents requiring specialized and timely outpatient care may be a major concern under pandemic conditions.

Value of a web-based pediatric drug information system to prevent serious adverse drug reactions in child and adolescent psychiatry.

Psychotropic drugs are frequently prescribed 'off-label' to children and adolescents and carry the risk of serious adverse drug reactions (sADR). We examined the frequency of sADRs of psychotropic drugs in pediatric inpatients and explored their potential preventability through following the recommendations of a web-based pediatric drug information system (PDIS). The potential socio-economic impacts of using this online system is also addressed. Routine clinical data from all inpatients treated in a child and adolescent psychiatry department between January 2017 and December 2018 were retrospectively examined for the occurrence of sADRs as defined by the European Medicines Agency. The preventability of the sADRs was assessed based on the information of the PDIS. Furthermore, the expected prolongation of the hospital stay due to sADRs was calculated as well as the associated treatment costs. The study was supported by the Innovation Fund of the Joint Federal Committee, grant number 01NVF16021. In total, 1036 patients were screened of whom 658 (63.5%) received psychopharmacological treatment. In 53 (8.1%) of these patients 54 sADRs were documented, of which 37 sADRs were identified as potentially preventable through PDIS. Mitigating sADR through PDIS would likely have prevented prolonged hospital stays and conferred considerable savings for health insurance companies. PDIS provides systematic and evidence-based information about pediatric psychopharmacotherapy and helps to prevent prescribing errors. Therefore, PDIS is a useful tool to increase drug therapy safety in child and adolescent psychiatry. Further prospective studies are needed to confirm the results.

Serious Adverse Drug Reactions to Antipsychotics in Minors with Multiple Disabilities: Preventability and Potential Cost Savings by Therapeutic Drug Monitoring.

INTRODUCTION: Children and adolescents with multiple disabilities and mental disorders (CAMD) are frequently treated with antipsychotic drugs. However, CAMD are particularly susceptible to serious adverse drug reactions (sADRs). This retrospective study examined the frequency of sADRs to antipsychotics in CAMD. Further, the potential preventability of these sADRs through therapeutic drug monitoring (TDM) and the potential socio-economic benefits of TDM were explored. METHODS: Routine clinical data of all patients treated at a specialized psychiatric clinic for CAMD between January 2017 and December 2018 were retrospectively examined. Data on the occurrence of sADRs (definition according to the European Medicines Agency), their causality with antipsychotics, as well as their preventability (Schumock criteria) were extracted from patient files. The prolongation of the hospital stay due to sADRs was calculated, and the cost savings were estimated if TDM had been applied. The data were based on a subsample of the KiDSafe project, supported by the Innovation Fund of the Joint Federal Committee, grant number 01NVF16021. RESULTS: One hundred two CAMD who were administered at least one antipsychotic drug during inpatient treatment were identified. Of these patients, 22 (21.6%) sADRs with a possible causal relationship with the antipsychotic treatment were documented. Eleven sADRs (50%) could potentially have been prevented through TDM. Mitigating sADRs through TDM likely would have prevented prolonged hospital stays and thus conferred considerable savings for health insurance companies. DISCUSSION: The routine implementation of TDM is urgently recommended for antipsychotic treatment in CAMD to increase drug therapy safety.

Therapeutic drug monitoring in adolescents with anorexia nervosa for safe treatment with adjunct olanzapine.

OBJECTIVE: Medication is commonly used in anorexia nervosa (AN) despite largely missing high grade evidence. Olanzapine (OLZ) is the best-evidenced substance used off-label in this group, with conflicting outcome regarding BMI, clinical and safety parameters. Therefore, it is important to strictly assure quality of treatment with OLZ in AN by using 'Therapeutic Drug Monitoring' according to AGNP-guidelines, including serum levels and adverse drug reactions (ADRs) to support safety for adolescents with AN and attempt to generate an initial age- and disorder-specific therapeutic reference range. METHOD: Sixty-five adolescents with AN (aged 10-18) treated with OLZ (98% female; 97.5% AN-restricting-type) were prospectively observed, ADRs reported, and correlations between dosage and serum levels measured at trough level were calculated, a preliminary therapeutic range defined. RESULTS: Mean dosage of OLZ was 8.15 (SD: 2.91) mg and 0.19 (SD: 0.07) mg/kg respectively, average concentration was 26.57 (SD: 13.46) ng/mL. Correlation between daily dosage/dosage per kg and serum level was 0.72 (**p < 0.001)/0.65 (**p < 0.001), respectively. ADRs with impairment were rare (6.3%). 75% improved clinically (CGI). BMI increased significantly by 1.5 kg/m2 (t = 10.6, p < 0.001). A preliminary therapeutic reference range is 11.9 and 39.9 ng/mL. CONCLUSIONS: OLZ in the hands of specialists is a well-tolerated and safe treatment adjunct for adolescents with AN.

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.

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.

BDNF levels in adolescent patients with anorexia nervosa increase continuously to supranormal levels 2.5 years after first hospitalization.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) influences brain plasticity and feeding behaviour, and it has been linked to anorexia nervosa in numerous studies. Findings in mostly adult patients point to reduced serum BDNF levels in the acute stage of anorexia nervosa and rising levels with weight recovery. However, it is unclear whether this increase leads to normalization or supranormal levels, a difference that is potentially important for the etiology of anorexia nervosa and relapse. METHODS: We measured serum BDNF at admission (n = 149), discharge (n = 130), 1-year follow-up (n = 116) and 2.5-year follow-up (n = 76) in adolescent female patients with anorexia nervosa hospitalized for the first time, and in healthy controls (n = 79). We analyzed associations with body mass index, eating disorder psychopathology and comorbidities. RESULTS: Serum BDNF was only nominally lower at admission in patients with anorexia nervosa compared to healthy controls, but it increased continuously and reached supranormal levels at 2.5-year follow-up. BDNF was inversely associated with eating disorder psychopathology at discharge and positively associated with previous weight gain at 1-year follow-up. LIMITATIONS: We compensated for attrition and batch effects using statistical measures. CONCLUSION: In this largest longitudinal study to date, we found only nonsignificant reductions in BDNF in the acute stage of anorexia nervosa, possibly because of a shorter illness duration in adolescent patients. Supranormal levels of BDNF at 2.5-year follow-up could represent a pre-existing trait or a consequence of the illness. Because of the anorexigenic effect of BDNF, it might play an important predisposing role for relapse and should be explored further in studies that test causality.

Dose-Corrected Serum Concentrations and Metabolite to Parent Compound Ratios of Venlafaxine and Risperidone from Childhood to Old Age.

OBJECTIVE: Comparative pharmacokinetic data about the antidepressant venlafaxine (VEN) and the antipsychotic drug risperidone (RIS) over the lifespan and especially in children and adolescents is lacking. This is the first cross-sectional study that aimed to investigate differences in dose-corrected serum concentrations (CDs) and metabolite to parent compound ratios (MPRs) of VEN and RIS across the lifespan. METHODS: Patients treated with VEN and RIS at the University Hospital of Würzburg, Germany were included in the study. Serum level determinations were performed during clinical routine care. Patients with CYP2D6 influencing co-medication were excluded from analyses. RESULTS: In 953 patients (12-93 years) treated with VEN and 552 patients (7-92 years) treated with RIS, children/adolescents (<18 years) showed 11% and 19%, and 44% and 42% lower CDs of the active moieties (CDsAM) of VEN and RIS than adults and elderly (≥60 years) (Kruskal-Wallis tests; p ≤ 0.001). However, when CDs were normalized to body weight, a different pattern emerged. Gender differences, with higher CDsAM in females were present in adults and elderlies but not in children/adolescents. No gender- or age-dependent difference in MPRs was found; however, 80% of MPRs of RIS in children/adolescents were below the range of "normal" CYP2D6 function for adults. CONCLUSIONS: We suggest a higher clearance as a reason for lower CDsAM of VEN and RIS in children/adolescents compared to adults/elderlies. Metabolism of VEN or RIS by CYP2D6, characterized by MPRs, was not associated with age. However, MPRs of RIS were lower in children/adolescents, possibly due to a higher renal clearance of 9-OH-risperidone.

Age dependency of body mass index distribution in childhood and adolescent inpatients with anorexia nervosa with a focus on DSM-5 and ICD-11 weight criteria and severity specifiers.

Both DSM-5 and ICD-11 have provided weight cut-offs and severity specifiers for the diagnosis of anorexia nervosa (AN) in childhood, adolescence and adulthood. The aims of the current study focusing on inpatients aged < 19 years were to assess (1) the relationship between age and body mass index (BMI; kg/m2), BMI-centiles, BMI-standard deviation scores (BMI-SDS) and body height-SDS at referral, (2) the percentages of patients fulfilling the DSM-5 and ICD-11 weight criteria and severity categories for AN, and (3) the validity of the AN severity specifiers via analysis of both weight related data at discharge and inpatient treatment duration. The German Registry for Anorexia Nervosa encompassed complete data sets for 469 female patients (mean age = 15.2 years; range 8.9-18.9 years) with a diagnosis of AN (n = 404) or atypical AN (n = 65), who were ascertained at 16 German child and adolescent psychiatric hospitals. BMI at referral increased up to age 15 to subsequently plateau. Approximately one tenth of all patients with AN had a BMI above the fifth centile. The ICD-11 specifier based on a BMI-centile of 0.3 for childhood and adolescent AN entailed two equally sized groups of patients. Discharge data revealed limited validity of the specifiers. Height-SDS was not correlated with age thus stunting had no impact on our data. We corroborate the evidence to use the tenth instead of the fifth BMI-centile as the weight criterion in children and adolescents. Weight criteria should not entail major diagnostic shifts during the transition from adolescence to adulthood. The severity specifiers based on BMI or BMI-centiles do not seem to have substantial clinical validity.

[Therapeutic drug monitoring to optimize psychopharmacotherapy in children and adolescents - Update and guidelines for practice]. / Therapeutisches Drug Monitoring zur Optimierung der Psychopharmakotherapie von Kindern und Jugendlichen.

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

Therapeutic drug monitoring of children and adolescents treated with aripiprazole: observational results from routine patient care.

Although aripiprazole is one of the most used antipsychotics, knowledge about serum concentrations in children and adolescents is scarce and age-specific therapeutic ranges have not been established yet. Data of a routine therapeutic drug monitoring service were analyzed in order to evaluate the relationship between dose and serum concentration of aripiprazole in children and adolescents. The study also aimed to evaluate whether the therapeutic reference range defined for adults with schizophrenia (100-350 ng/ml) is applicable for minors. Data from 130 patients (aged 7-19 years) treated with aripiprazole for different indications in doses of 2-30 mg/day were evaluated. Patient characteristics, doses, serum concentrations and therapeutic outcome were assessed by standardized measures. A positive mean correlation between body weight-corrected daily dose and aripiprazole concentration was found (rp = 0.59, p < 0.001) with variation in dose explaining 35% of the variability in serum concentrations. Girls had on average 41% higher dose-corrected concentrations than boys (244.9 versus 173.4 mg/l; p = 0.006). Aripiprazole concentrations did not vary with co-medication (p = 0.22). About 70% of all measured serum concentrations were within the recommended therapeutic range for adults. Using a calculation method in all responding patients with an ICD-10 F2 diagnosis for a rough estimation of a preliminary therapeutic window also demonstrated a similar therapeutic range of aripiprazole in minors (105.9-375.3 ng/ml) than for adults. If confirmed in larger samples and more controlled study designs, these data may contribute to the definition of a therapeutic range of aripiprazole concentrations in children and adolescents.

Incontinence and constipation in adolescent patients with anorexia nervosa-Results of a multicenter study from a German web-based registry for children and adolescents with anorexia nervosa.

OBJECTIVE: Nocturnal enuresis (NE), daytime urinary incontinence (DUI), and fecal incontinence (FI) are common disorders in childhood and are frequently accompanied by comorbid psychiatric disorders. Despite a high association between urinary and fecal incontinence with psychiatric and neurodevelopmental disorders, research on comorbidity between incontinence and anorexia nervosa (AN) remains scarce. Yet, it is well known that somatic consequences of AN include metabolic and gastrointestinal disorders. The study sought to assess the prevalence of incontinence and constipation in children and adolescents with AN and to examine associations of these two symptoms with body weight at admission and with BMI changes during inpatient treatment. METHODS: Data collected between 2015 and 2017 by a multicenter German web-based registry for AN were analyzed. Three hundred and forty-eight patients with AN (96.3% female, mean age = 15.1 ± 1.8 years) were assessed regarding AN subtype, psychiatric comorbidity, body weight, incontinence, and constipation. RESULTS: Overall, 27.6% of patients had constipation, 1.8% had NE and 1.8% DUI. Prevalence of constipation did not significantly differ between AN subtypes. Constipation did not lead to any significant differences in weight/BMI changes during inpatient treatment. DISCUSSION: This is the largest study of incontinence and constipation in patients with AN, so far. Our results indicate that constipation is highly prevalent in adolescent patients with AN and reflects a clinically relevant condition. Despite, patients with AN do not have an increased prevalence of incontinence compared with the general population. Future studies should include medical examinations like ultrasound and physical examination of the lower abdomen to evaluate the severity of constipation.

[Therapeutic drug monitoring in neuropsychopharmacology : Summary of the consensus guidelines 2017 of the TDM task force of the AGNP]. / Therapeutisches Drug-Monitoring in der Neuropsychopharmakologie : Zusammenfassung der Konsensusleitlinien 2017 der TDM-Arbeitsgruppe der AGNP.

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood serum or plasma to optimize pharmacological therapy. TDM is an instrument with which the high interindividual variability of pharmacokinetics of patients can be identified and therefore enables a personalized pharmacotherapy. In September 2017 the TDM task force of the Working Group for Neuropsychopharmacology and Pharmacopsychiatry (AGNP) published an update of the consensus guidelines on TDM published in 2011. This article summarizes the essential statements for the clinical practice in psychiatry and neurology.

Non-Fatal Intoxication with a High Dose of Citalopram in a Suicidal 14-Year-Old Girl.

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

[Polypharmacy of psychotropic drugs in child and adolescent psychiatry in Germany - rather the rule than the exception]. / Polypharmazie in der Anwendung von Psychopharmaka in der deutschen Kinder- und Jugendpsychiatrie ­ häufiger Regel als Ausnahme.

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

Outcome of childhood anorexia nervosa-The results of a five- to ten-year follow-up study.

OBJECTIVE: Although admissions of children with anorexia nervosa (AN) are increasing, there remains a dearth of up-to-date knowledge of the course and outcome of early-onset AN. The aim of the present study was to investigate the outcomes of patients with AN onset before the age of 14. METHOD: Sixty-eight consecutive former patients who met the DSM-IV criteria for AN and who had been treated at one of three German university hospitals were asked to participate in a follow-up study. Body mass index, body height, outcome of the eating disorder (ED), psychiatric morbidity, and health related quality of life (HRQoL) were assessed through a personal examination after an average time span of 7.5 years (range: 4.5-11.5 years) after admission. RESULTS: One patient had died. Fifty-two subjects with a mean age of 12.5 (SD 1.0) years at admission and of 20.2 (SD 2.0) years at follow-up agreed to participate in the follow-up assessment, aggregating to 77.9% of the original sample. Approximately 41% of the participants had a good outcome, while 35% and 24% had intermediate and poor outcomes, respectively. Twenty-eight percent of the sample met the DSM-IV criteria for a current non-ED psychiatric disorder, and 64% met the criteria for a past non-ED psychiatric disorder. Mental HRQoL and ED-specific psychopathology was strongly associated with the outcome of AN. Average body height was below the normal range. A higher weight at admission was the only significant positive indicator of outcome. DISCUSSION: Childhood AN is a serious disorder with an unfavorable course in many patients and high rates of chronicity and psychiatric comorbidity in young adulthood. Early detection and intervention are urgently needed.

Therapeutic Drug Monitoring in Children and Adolescents Under Pharmacotherapy With Olanzapine in Daily Clinical Practice.

BACKGROUND: The relationship between daily dose, serum concentrations, and clinical outcomes of olanzapine as well as the influencing factors thereof in children and adolescents treated for different psychiatric disorders were investigated in daily clinical practice. In addition, it was examined whether the current recommended therapeutic range (TR) for adult patients with psychotic disorders is valid for minors. METHODS: The Competence Network for Therapeutic Drug Monitoring (www.tdm-kjp.com) routinely collects demographic and clinical outcome data as well as serum concentrations of children and adolescents treated with psychotropics. The therapeutic effect is documented using the Clinical Global Impression Scale subscale for Global Improvement. Adverse drug reactions (ADRs) are assessed using the Udvalg for Kliniske Undersogelser-Side Effect Rating Scale. RESULTS: One hundred fifteen patients (mean age = 15.9 years; range = 10.4-18.8 years; 40.9% male) were included. The majority (72.1%) was cotreated with other psychotropic drugs. A positive medium linear relationship (r = 0.619; P < 0.001) between olanzapine dose (mean = 11.64 mg/d) and serum concentration (mean = 35.65 ng/mL) was found with a marked interindividual variability of serum concentrations. Neither relationship between olanzapine serum concentration and treatment response (clinical benefit documented in 80%) nor ADRs (documented in 53.3%, in 7.5% judged as severe) was detected. Most of the patients with psychotic and eating disorders (68.8% and 71.8%, respectively) had an olanzapine serum concentration within the TR suggested for adults. CONCLUSIONS: There are several limitations of this study because of the naturalistic design, and our results should therefore be interpreted with caution. As most of the patients showed a clinical benefit under olanzapine concentrations within the TR for adults and only a minority had severe ADRs, it is reasonable to conclude a similar TR for children, adolescents, and adults.

Relationship Between Daily Dose, Serum Concentration, and Clinical Response to Quetiapine in Children and Adolescents with Psychotic and Mood Disorders.

Introduction In child and adolescent psychiatry, therapeutic drug monitoring (TDM) is strongly recommended. However, therapeutic ranges (TR) are defined only for adults. The objectives of this naturalistic study were to assess the relationships between serum quetiapine concentration, daily dose, and clinical outcomes as well as the determinants of pharmacokinetic variability. Furthermore, it was elucidated whether the recommended TR for adult patients with psychotic disorders is valid for children and adolescents. Methods TDM was performed in 180 pediatric patients treated with quetiapine. Psychopathological changes were assessed by the Clinical Global Impression - Improvement scale (CGI-I). Adverse drug reactions (ADRs) were assessed by using a short form of the Udvalg for Kliniske Undersogelser (UKU) side effect rating scale. Results A weak positive linear relationship between daily dose (mean 349.9±248.9 mg/day) and serum concentration of quetiapine (rs=0.496, p<0.001) was found (mean age 15.6±1.9 years, 45.6% male, 31.1% monotherapy), but no relationship between serum concentration and clinical outcome was found. Dose variation accounted for only 12.5% (rs2=0.125) of the variability of serum concentrations. No effects by gender, age, body weight, smoking habits, and co-medication were found. The majority of patients with psychotic (67.8%) and mood disorders (74.5%) showed a serum concentration below the suggested lower limit (100 ng/mL) of the TR for adults. Discussion There are several limitations of this study because of the naturalistic design, and our results should therefore be interpreted with caution. Notwithstanding, our data suggest that the lower limit of the TR for quetiapine is lower than the limit in adult patients.

Expressed Emotions and Depressive Symptoms in Caregivers of Adolescents with First-Onset Anorexia Nervosa-A Long-Term Investigation over 2.5 Years.

OBJECTIVE: High levels of expressed emotions (EE) and depressive symptoms (DS) are often found in caregivers of patients with anorexia nervosa (AN). Both parameters are considered to influence AN symptoms of the patient. METHODS: One hundred seventy adolescent women with AN and their caregivers were assessed at admission, discharge, at 1-year and 2.5-year follow up to evaluate AN symptoms of the patient and EE and DS of caregivers. RESULTS: The EE and DS were elevated at admission and decreased during treatment, criticism (as part of EE) exhibited again at the 2.5-year follow up. Caregivers of more severely ill patients reported significantly greater levels of EE and DS. Mothers were more affected than fathers. EE and DS were interrelated. CONCLUSION: Caregivers of adolescent AN patients suffer from elevated levels of EE and DS. Further studies are needed to examine whether therapeutic interventions to reduce caregivers' EE and DS might have a positive influence on treatment outcome. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.