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.

The adaptation and evaluation of a CBT-based manual for the inpatient treatment of youth depression: a pilot study.

BACKGROUND: Although there is good evidence to support the effectiveness of cognitive behavioral therapy (CBT) for the outpatient treatment of adolescent major depressive disorder (MDD), evidence-based manuals for the inpatient setting are lacking. This pilot study sought to (i) adapt an existing CBT manual (treatment of adolescent depression; TADS) to an inpatient setting (TADS-in), (ii) test its effectiveness at symptom reduction and remission of MDD in a pre-post design, and (iii) assess the strengths and limitations of the manual via a focus-group with clinicians. METHODS: Twenty nine adolescents aged 12-17 years with a primary ICD-10 diagnosis of MDD being treated as inpatients at a psychiatric clinic were included. Embedded in the regular inpatient treatment course (8 weeks), patients received 12 sessions of the TADS-in manual. Quantitative assessment of symptom reduction and remission of MDD was conducted using a non-controlled pre-post design. The quantitative results were supplemented by a focus group with participating psychotherapists. RESULTS: Of the 29 patients included in the study at the beginning, 19 (65.5%) remained in the study at week 8. Symptoms of depression were statistically significantly lower at the end of treatment than at baseline according to self- (d = 1.38; mean change = 19.88; 95% CI = 12.48-27.28) and other reports (d = 0.64, mean change = 0.35; 95% CI = 0.08-0.62). Clinicians ratings of improvement (CGI-I) suggested that at the end of treatment, 15.8% were very much improved, 68.4% much improved, and 15.8% were minimally improved. According to diagnostic interviews with patients conducted at the end of treatment, 73.3% were in remission. The qualitative analysis showed that on the whole, the TADS-in manual is suitable for the inpatient setting. However, clinicians believed the effectiveness of TADS-in was limited by patient comorbidity and the fact that the inpatients were unable to practice incorporating techniques learnt into everyday life. CONCLUSIONS: This study is the first to adapt the TADS manual to the inpatient setting. The sample of depressed adolescents showed reduced symptomology following treatment, although these findings require replicating in a randomized controlled trial before effects can be attributed to the TADS-in manual specifically. This pilot study informs further development of the manual as well as representing an important first step in the evaluation of the inpatient treatment of adolescent depression.The study was retrospectively registered (DRKS00017308) and received no external funding.

Nonsuicidal self-injury and its relation to personality traits in medical students.

Nonsuicidal self-injury (NSSI) has a high prevalence among the general undergraduate population, but as yet, no study has investigated the rate of NSSI among medical students despite the high levels of depression and suicidal ideation found in this population. Our study aimed to estimate the prevalence of NSSI and suicide attempts in German medical students and explore the associations between these behaviors and the five major personality traits. Seven hundred fourteen medical students (67% women; age range, 18-35 years; mean age, 23.1 years) participated in an online survey. We report a lifetime prevalence of 14.3% for NSSI and 1.5% for suicide attempt. The students with NSSI showed higher levels of neuroticism and openness to experience but lower levels of conscientiousness and extraversion on the NEO Five-Factor Inventory. Our results are in line with previous research from other countries regarding the prevalence of NSSI among students and its association with personality.

[Integrating the e-learning programme EGONE into the block of training in obstetrics and gynaecology]. / Integration des E-Learning-Programmes EGONE in das Blockpraktikum der Gynäkologie/Geburtshilfe.

OBJECTIVE: EGONE is an E-Learning Forum for Gynaecology, Obstetrics, Neonatology and Reproductive Endocrinology based on the Swiss Catalogue of Learning Objectives. For two semesters, students attending the gynaecology block at the Medical Faculty of the University of Ulm have been provided with licences to use EGONE. Students can work on a specially equipped computer and practise whenever they want. The aim of this study was to generate hypotheses as to which factors favour the use of EGONE and which didactic implications for the learning success the application of EGONE has. METHODS: During August 2009, 28 medical students in their 8th and 9th semester were interviewed after having completed their block of training in gynaecology. The instruments used included a questionnaire and a partially standardised interview. RESULTS: We found that the e-learning offering EGONE was basically met with a positive response from the medical students at the University of Ulm. Regarding the integration of EGONE, three problem areas were identified: shortage of equipment, lack of dependable access and functional, but not curricular integration. Students' suggestions for better integration of EGONE were related to two subject areas: establishing an assisted learning centre (e.g., PC pool with library) and developing curricular independence and relevance (e.g., specific application to patient cases, conducting seminars with EGONE). CONCLUSION: The integration of the e-learning programme EGONE presupposes a logical, didactic concept for the whole clinical block of training in gynaecology as well as dependable, sufficient infrastructure and technical equipment and providing didactic support to users.

[Introduction of the module "Evidence-based Medicine" in Child and Adolescent Psychiatry into the psychiatry block practicum at the University of Ulm]. / Einführung eines Moduls "Evidenz-basierte Medizin in der Kinder- und Jugendpsychiatrie" in das Blockpraktikum Psychiatrie an der Universität Ulm.

OBJECTIVE: The essential need for the timely availability of additional relevant information has resulted in a focus on "Evidence-based Medicine" (EBM) in medical practice. In Child and Adolescent Psychiatry (CAP) training it is essential to impart knowledge of how to effectively use the available literature, since the evidence for many therapies is still poor. METHOD: We modified the "Duke Model" for teaching EBM in CAP to better attune it to the educational needs of a German university. We describe the introduction of the teaching module "Evidence-based Medicine in CAP" in practical clinical training. RESULTS: Integrating EBM into mandatory practical training enables the students to deal with problems that directly pertain to patient treatment, thus motivating them to access and read relevant scientific literature. An initial evaluation of this pilot project shows the successful linkage of research with clinical routine and also the conveyance of improved decision making abilities as well as an attitude of life-long learning. CONCLUSIONS: Modifying the EBM-module for practical clinical training is an innovative approach to integrating EBM into medical curricula. In the course of a curricular reform, "EBM cross sectional training" for all medical students was introduced into the new curriculum of the Medical School at the University of Ulm.

[Docs'n Drugs--an E-learning program for medical students; feasibility and evaluation of the acceptance in student training in child and adolescent psychiatry at the University Hospital in Ulm]. / E-learning mit Docs'n Drugs--Anwendung und Akzeptanz in der Kinder- und Jugendpsychiatrie der Universität Ulm.

OBJECTIVE: Increasingly widespread is the use of modern media such as E-learning in medical education. The Medical Faculty of the University of Ulm, being the Competence Center of E-learning, and the Competence Network in Medical Education in Baden-Württemberg have been developing a web based multimedia educational program since 1998. METHODS: In 2004 a grant for modular teaching projects sponsored by the Medical School was obtained in order to incorporate cases from Child and Adolescent Psychiatry into the Docs'n Drugs E-learning Module. The objective was to explore the feasibility of adding psychiatric cases to an educational system that was primarily oriented towards somatic diseases and to then evaluate the acceptance of these child and adolescent psychiatric cases. RESULTS: Once cases had been developed, this module was integrated into Docs'n Drugs as a one-and-a-half hour web-based seminar as part of a block practicum in child and adolescent psychiatry and subsequently evaluated. The evaluation included data from 69 participants between summer 2004 and spring 2006. Of the participating students, 80.8% had never used the E-learning platform together with a monitor in a seminar before. 44.9%, respectively 41%, of the students responded that psychiatric cases could be dealt with in a good or partially satisfying way with that system. This gives an overall positive acceptance of 86%. CONCLUSIONS: Our evaluated feasibility trial with a child psychiatric module within an E-learning based teaching platform showed that knowledge not only of somatic cases but also of psychiatric cases can be imparted via E-learning. The integration into an existing curriculum is advisable in any case.