Sex-Specific Differences in Antidepressant and Antipsychotic Treatment Outcomes and Serum Levels in Children and Adolescents.

Sex-specific differences in psychopharmacological treatment have gained increasing attention in adults, with studies showing that women often have higher serum concentrations of psychotropic drugs due to biological differences. However, despite recognition of these differences in adults, reference ranges for therapeutic drug monitoring (TDM) in general, but even more sex-specific therapeutic windows for psychotropic drugs, are lacking in children and adolescents, who may metabolize and respond to medications differently. The study aimed to investigate sex-specific differences in antidepressant (AD) and antipsychotic (AP) -treatment outcomes, and pharmacokinetics in childhood/adolescence.

Efficacy of Adjunct Olanzapine Treatment in Adolescents With Anorexia Nervosa: A Comparison of Two Patient Cohorts.

Background: Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality, requiring innovative treatment strategies. Olanzapine (OLZ), an atypical antipsychotic, has demonstrated efficacy in promoting weight gain and reducing psychopathological symptoms in adults with AN. However, its efficacy and safety in adolescents remain insufficiently explored.

External validation of a therapeutic window for risperidone in children with autism spectrum disorder.

Although risperidone is an effective pharmacological intervention for managing disruptive behaviour in children with autism spectrum disorder, it may induce metabolic side effects. This study aimed to externally validate the population pharmacokinetic (popPK) model and the therapeutic window of 3.5-7 ng/mL of risperidone and 9-OH-risperidone, developed with data of the SPACe Study.

No indications of weight gain associated DNA methylation changes in patients with anorexia nervosa.

Anorexia nervosa (AN) is a mental disorder marked by a significantly low body weight. Differentially methylated CpG sites have been reported to be involved in body weight regulation. Methylation pattern may change during considerable weight gain by in-patient treatment.

Medication Nonadherence in Children and Adolescents with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) affects 6-10 % of children and adolescents worldwide. While psychopharmacological treatments effectively reduce symptoms, incomplete adherence is common, diminishing their effectiveness. This study investigated medication nonadherence and its predictors in children and adolescents with ADHD.

Genome-wide association studies of binge eating behaviour and anorexia nervosa yield insights into the unique and shared biology of eating disorder phenotypes.

Eating disorders -including anorexia nervosa (AN), bulimia nervosa, and binge eating disorder-are clinically distinct but exhibit symptom overlap and diagnostic crossover. Genomic analyses have mostly examined AN. We conducted the first genomic meta-analysis of binge eating behaviour (BE; 39,279 cases, 1,227,436 controls), alongside new analyses of AN (24,223 cases, 1,243,971 controls) and its subtypes (all European ancestries).

Serum Concentration-Dose Relationship and Modulation Factors in Children and Adolescents Treated with Fluvoxamine.

Introduction: Fluvoxamine is used in children and adolescents ('youths') for treating obsessive compulsive disorder (OCD) but also off-label for depressive and anxiety disorders. This study aimed to investigate the relationship between fluvoxamine dose and serum concentrations, independent correlates of fluvoxamine concentrations, and a preliminary therapeutic reference range (TRR) for youths with OCD and treatment response.

Methods: Multicenter naturalistic data of a therapeutic drug monitoring service, as well as prospective data of the 'TDM Vigil study' (EudraCT 2013-004881-33), were analyzed.

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.

Unexpected identification of obesity-associated mutations in LEP and MC4R genes in patients with anorexia nervosa.

Mutations leading to a reduced or loss of function in genes of the leptin-melanocortin system confer a risk for monogenic forms of obesity. Yet, gain of function variants in the melanocortin-4-receptor (MC4R) gene predispose to a lower BMI. In individuals with reduced body weight, we thus expected mutations leading to an enhanced function in the respective genes, like leptin (LEP) and MC4R.

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 ( = 138; mean age, 15; range, 7-18 years; 24.

Clinical pharmacokinetics of antipsychotics in pediatric populations: a scoping review focusing on dosing regimen.

Introduction: Achieving optimal clinical responses and minimizing side effects through precision dosing of antipsychotics in children and adolescents with psychiatric disorders remains a challenge. Identifying patient characteristics (covariates) that affect pharmacokinetics can inform more effective dosing strategies and ultimately improve patient outcomes. This review aims to provide greater insight into the impact of covariates on the clinical pharmacokinetics of antipsychotics in pediatric populations.

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.

Therapeutic Reference Range for Olanzapine in Schizophrenia: Systematic Review on Blood Concentrations, Clinical Effects, and Dopamine Receptor Occupancy.

Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and dopamine D-receptor occupancy for oral and long-acting injectable (LAI) formulations. Databases were systematically searched for randomized controlled trials (RCTs) and uncontrolled trials concerning blood olanzapine levels in relation to clinical outcomes or D-receptor occupancy using MEDLINE (PubMed), Web of Science, PsycINFO, and Cochrane Library (March 2021, updated in December 2021). We excluded articles not written in English or German and non-human data.

Lipocalin 2 - mutation screen and serum levels in patients with anorexia nervosa or obesity and in lean individuals.

Context: The bone-derived adipokine lipocalin-2 is relevant for body weight regulation by stimulating the leptin-melanocortin pathway.

Objective: We aimed to (i) detect variants in the lipocalin-2 gene () which are relevant for body weight regulation and/or anorexia nervosa (AN); (ii) describe and characterize the impact of and variants on circulating lipocalin-2 level.

Methods: Sanger sequencing of the coding region of in 284 children and adolescents with severe obesity or 287 patients with anorexia nervosa.

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.

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.

PTBP2 - a gene with relevance for both Anorexia nervosa and body weight regulation.

Genetic factors are relevant for both eating disorders and body weight regulation. A recent genome-wide association study (GWAS) for anorexia nervosa (AN) detected eight genome-wide significant chromosomal loci. One of these loci, rs10747478, was also genome-wide and significantly associated with body mass index (BMI).

[Therapeutic drug monitoring to optimize psychopharmacotherapy in children and adolescents - Update and guidelines for practice].

Therapeutic drug monitoring to optimize psychopharmacotherapy in children and adolescents - Update and guidelines for practice 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.

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.

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.