[Sleep in patients of a memory clinic : Clinical characteristics of the discrepancy between subjective and objective assessment]. / Schlaf bei Patienten einer Gedächtnissprechstunde : Klinische Charakteristika der Diskrepanz zwischen subjektiver und objektiver Erfassung.

BACKGROUND: Dementia is often accompanied by sleep disturbances, whereby the diagnostics with subjective procedures and objective methods can produce discrepant results. The frequency and clinical characteristics of patients, whose subjective sleep efficiency was unimpaired and was in contrast to an objectively conspicuous sleep efficiency in the sense of an overestimation, were investigated in a memory consultation. METHODS: On 2 consecutive days, patients underwent guideline-oriented diagnostics for dementia (including mini-mental status examination, MMSE and clinical dementia rating, CDR), supplemented by a subjective (Pittsburgh sleep quality index, PSQI) and objective (overnight actigraphy) sleep assessment. Overestimation of sleep efficiency was defined as a subjective sleep efficiency (SSE) of ≥85% with an actigraphic sleep efficiency (ASE) of <85%. RESULTS: Of 45 patients (74.4 ± 7.8 years; 26 f/19 m; CDR < 1: n = 16, CDR = 1: n = 28; diagnostic groups according to ICD-10: F0: n = 39, F3: n = 5, Z03.x: n = 1) 10 showed an overestimation of sleep efficiency, who showed a lower MMSE score and a higher proportion of patients with a dementia syndrome (CDR = 1) when compared with the other three groups of SSE and ASE ≥85% (n = 17), SSE and ASE <85% (n = 9) and SSE <85% with ASE ≥85% (n = 9). Binary regression showed that MMSE remained an important predictor for overestimation of sleep efficiency. CONCLUSION: Cognitive deficits in memory clinic patients appear to contribute to a poorer perception and/or an underreporting of objectively disturbed sleep. This could promote false negative subjective screening results in a diagnostic process in which a comprehensive sleep assessment is not routinely considered.

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017.

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

The reproducibility and clinical utility of the 3D camera for measuring scar height, with a protocol for administration.

BACKGROUND: This study aimed to determine the reproducibility and clinical utility of a 3D camera for measuring burn scar height in adults. METHODS: Participants from a larger prospective longitudinal study were included. Reproducibility data were collected using an immediate test-retest interval and a 1-2 week test-retest interval and included reliability and agreement. The LifeViz™ 3D camera was used to measure scar height. Reproducibility was tested using the Intraclass Correlation Coefficient (ICC), percentage agreement within 1 mm between test and retest, standard error of measurement, smallest detectable change (SDC) and Bland Altman limits of agreement. RESULTS: Burn scar images from 55 adult participants were included. Intra-rater reliability was acceptable using an immediate retest interval (maximum and minimum height ICC=0.85, 0.86 respectively). Agreement using an immediate retest interval was borderline acceptable (maximum and minimum height SDC=1.11, 0.69 respectively) to detect changes of close to 1 mm. Reproducibility was largely not acceptable using a 1-2 week test-retest interval (eg, maximum and minimum height ICC=0.34, 0.68 respectively; maximum and minimum height SDC=2.66, 1.16). The clinical utility of the camera was supported for scars over relatively flat areas and well-defined border margins. A protocol for administration of the camera was developed. CONCLUSION: The 3D camera appears capable of detecting gross changes or differences in scar height above the normal skin surface, in adults with scars over relatively flat areas and well-defined border margins. However, further testing of reproducibility using a shorter test-retest interval than 1-2 week retest is recommended to confirm the suitability of the device for measuring changes or differences in scar height.

[Multiprofessional inpatient psychotherapy of depression in old age]. / Multiprofessionelle stationäre Psychotherapie bei Depressionen im Alter.

Depression is common in old age but is often underdiagnosed and inadequately treated. Although psychotherapy is considered effective for treating elderly patients with depression, it is rarely applied in inpatient settings. Furthermore, treatment on inpatient units specialized for elderly patients and implementation of a psychotherapeutic treatment approach are currently more the exception. From this background, a multiprofessional inpatient behavioral treatment program (MVT) for elderly depressed patients was developed at a specialized unit of a university-affiliated regional psychiatric hospital. The MVT is based on specific and modularized group therapies accompanied by individual therapeutic interventions. While the provision of group therapies (such as psychotherapy, social skills training, relaxation training, euthymic and mindfulness-based methods, exercise and occupational therapy as well as psychoeducational sessions for relatives) is assigned to specific professional groups, a joint multiprofessional treatment planning is of central relevance. First evaluations of different treatment components support the high acceptability of the MVT and highlight that psychotherapeutic inpatient treatment programs for the elderly are feasible. Further research is required to investigate the clinical efficacy of psychotherapy in elderly depressive inpatients.

[Rank of outcome parameters in the treatment of depression : Results of a Delphi panel survey]. / Präferenz von Zielparametern bei der Behandlung der Depression : Ergebnisse einer Delphi-Panel-Erhebung.

BACKGROUND: In the context of new drug benefit assessments a list of outcome parameter are evaluated. Currently it is unclear, how different outcome parameters are weighed in the overall assessment. OBJECTIVES: The objective of the survey is to rank relevant outcome parameters in the treatment of depression, which may be considered in benefit the assessment of new antidepressants. MATERIALS AND METHODS: In 2015 a Delphi panel survey with 30 general practitioners and specialists in Germany was performed regarding the benefit assessment of antidepressants. On the basis of two fictive casuistics (patients with depressive disorders) the physicians weighed a range of relevant outcome parameters regarding efficacy, quality of life, safety and tolerability according to their relevance to clinical practice. RESULTS: Regarding efficacy, response, remission and recovery were rated as the most important outcomes. Regarding quality of life, handling of the daily household activities and mental performance were rated as most important. Suicidality was rated as the most important outcome regarding safety and tolerability. CONCLUSIONS: Individual outcome parameters were rated differently by the physicians regarding their relevance to clinical practice. The results indicate that outcome parameters should be weighed differently when assessing the overall benefit of new antidepressants.

[Current Guidelines to Prevent Obesity in Childhood and Adolescence]. / Aktuelle Empfehlungen zur Prävention der Adipositas im Kindes- und Jugendalter.

BACKGROUND: Current guidelines for the prevention of obesity in childhood and adolescence are presented. METHODS: A literature search was performed in Medline via PubMed, and appropriate studies were analysed. RESULTS: Programs to prevent childhood obesity were to date mainly school-based. Effects were limited to date. Analyses tailored to different age groups show that prevention programs have the best effects in younger children (< 12 years). Evidence based recommendations for preschool- and early school age imply the need for interventions addressing parents and teachers alike. During adolescence, school-based interventions were most effective when adolescents were directly addressed. To date, obesity prevention programs have mainly focused on behavior oriented prevention. Recommendations for condition oriented prevention have been suggested by the German Alliance of Non-communicable Diseases and include one hour of physical activity at school, promotion of healthy food choices by taxing unhealthy foods, mandatory quality standards for meals at kindergarten and schools as well as a ban on unhealthy food advertisement addressing children. CONCLUSION: Behavior oriented prevention programs showed hardly any or only limited effects in the long term. Certain risk groups for the development of obesity are not reached effectively by available programs. Due to the heterogeneity of available studies, universally valid conclusions cannot be drawn. The combination with condition oriented prevention, which has to counteract on an obesogenic environment, is crucial for sustainable success of future obesity prevention programs.

[Required Effekt Sizes of Preventive Measures for Overweight in Children and Adolescents]. / Wie groß muss die Wirkung von Prävention auf das Übergewicht von Kindern und Jugendlichen sein?

BACKGROUND AND AIM OF THE STUDY: Successful preventive measures can stop a further increase in the prevalence of overweight in children and adolescents. However, up to now, the required effect sizes of interventions for reducing childhood overweight remain unclear. The calculation of the energy gap (excess calories consumed over calories expended) offers the possibility to estimate the required effect sizes. In this work 2 approaches to calculate the energy gap will be compared. METHODS: Longitudinal data of 1690 children and adolescents of the Kiel Obesity Prevention Study (KOPS) on measured height, weight, fat mass and fat-free mass (using bioelectrical impedance analysis) at age 6 and 10 years will be used to calculate energy gap with 2 different approaches: (i) using age-independent changes in fat mass and fat-free mass (old approach) and (ii) using a mathematic model of weight dynamic (new approach). RESULTS: Energy gap according to the old approach was 140 kcal/day; by contrast, new modeling resulted in an energy gap between 270 and 370 kcal/day. Both, BMI and fat mass were suitable to calculate energy gap and led to nearly same results. Exceeding the 90(th) percentile of BMI or fat mass (incidence approach) as well as large changes within the normal range (i.e. between the 10(th) and the 90(th) percentile) led to large energy gaps. Thus, all children with large energy gaps have to be characterized as at risk for overweight. CONCLUSION: The new approach seems to be convincing because it considered the additional energy expenditure for building fat-free mass due to increasing age and weight.Calculating energy gap offers a new approach for prevention of overweight. It shows that the required effect sizes of prevention measures have to be in a region of 140 to 400 kcal/day. This differs clearly from energy reduction of diets in the therapy of obesity.

Identification of skeletal muscle mass depletion across age and BMI groups in health and disease--there is need for a unified definition.

Although reduced skeletal muscle mass is a major predictor of impaired physical function and survival, it remains inconsistently diagnosed to a lack of standardized diagnostic approaches that is reflected by the variable combination of body composition indices and cutoffs. In this review, we summarized basic determinants of a normal lean mass (age, gender, fat mass, body region) and demonstrate limitations of different lean mass parameters as indices for skeletal muscle mass. A unique definition of lean mass depletion should be based on an indirect or direct measure of skeletal muscle mass normalized for height (fat-free mass index (FFMI), appendicular or lumbal skeletal muscle index (SMI)) in combination with fat mass. Age-specific reference values for FFMI or SMI are more advantageous because defining lean mass depletion on the basis of total FFMI or appendicular SMI could be misleading in the case of advanced age due to an increased contribution of connective tissue to lean mass. Mathematical modeling of a normal lean mass based on age, gender, fat mass, ethnicity and height can be used in the absence of risk-defined cutoffs to identify skeletal muscle mass depletion. This definition can be applied to identify different clinical phenotypes like sarcopenia, sarcopenic obesity or cachexia.

[GeKo KidS--Health Literacy in School Children]. / GeKo KidS--Gesundheitskompetenz bei Kindern in der Schule.

The main goal of this study was the evaluation of an intervention programme for the promotion of health literacy in school-aged children (grade 5-6). The project and the programme were highly accepted, the extension of the annual dental health examination was suitable to collect data within evaluation projects in schools. In spite of positive outcomes, a longer supervision phase would be necessary in order to optimise and to implement other programme components fully.

[Pharmacotherapy of psychiatric acute and emergency situations: General principles]. / Pharmakotherapie von psychiatrischen Akut- und Notfallsituationen : Allgemeine Prinzipien.

The pharmacotherapy of psychiatric emergencies is essentially determined by the acuteness, the scene of the emergency, the diagnostic assessment and the special pharmacological profile of the drug used. As there are no specific drugs, syndromic treatment is carried out. For this, primarily antipsychotic drugs and benzodiazepines are available. This article gives an overview of the current state of treatment options for major psychiatric emergency syndromes, namely agitation, delirium, stupor and catatonia, anxiety and panic, as well as drug-induced emergencies.

Effect of weight loss and regain on adipose tissue distribution, composition of lean mass and resting energy expenditure in young overweight and obese adults.

BACKGROUND: Although weight cycling is frequent in obese patients, the adverse consequences on body composition and an increased propensity to weight gain remain controversial. OBJECTIVE: We investigated the effect of intentional weight loss and spontaneous regain on fat distribution, the composition of lean mass and resting energy expenditure (REE). DESIGN: Weight regainers (≥ 30% of loss, n=27) and weight-stable subjects (within <± 20% of weight change, n=20) were selected from 103 overweight and obese subjects (body mass index 28-43 kg m(-2), 24-45 years) who passed a 13-week low-calorie diet intervention. REE and body composition (by densitometry and whole-body magnetic resonance imaging) were examined at baseline, after weight loss and at 6 months of follow-up. RESULTS: Mean weight loss was -12.3 ± 3.3 kg in weight-stable subjects and -9.0 ± 4.3 kg in weight regainers (P<0.01). Weight regain was incomplete, accounting for 83 and 42% of weight loss in women and men. Regain in total fat and different adipose tissue depots was in proportion to weight regain except for a higher regain in adipose tissue of the extremities in women and a lower regain in extremity and visceral adipose tissue in men. In both genders, regain in skeletal muscle of the trunk lagged behind skeletal muscle regain at the extremities. In contrast to weight-stable subjects, weight regainers showed a reduced REE adjusted for changes in organ and tissue masses after weight loss (P<0.001). CONCLUSION: Weight regain did not adversely affect body fat distribution. Weight loss-associated adaptations in REE may impair weight loss and contribute to weight regain.

Early improvement and serum concentrations of citalopram to predict antidepressant drug response of patients with major depression.

INTRODUCTION: Post hoc analyses of clinical trials have shown that early improvement around day 14 is highly predictive for later response. More-over, evidence has been given that sufficiently high concentrations of antidepressant drugs in blood are required to attain response. In this study, we determined cut-off levels for citalopram serum concentrations and clinical improvement during the early phase of treatment to predict later response and the predictive power of these measures either alone or in combination. METHODS: Inpatients with depressive disorder according to ICD-10 who received citalopram were included. Psychopathology was assessed by the 17-item Hamilton Depression (HAMD-17) rating scale, and serum concentrations of citalopram were measured in weekly intervals. RESULTS: The analysis included 55 inpatients. Receiver operating characteristics analysis revealed for citalopram a serum concentration of 53 ng/ml on day 7 and a clinical improvement of 24% on the HAMD-17 scale on day 14 as significant cut-off values to predict response after 5 weeks of treatment. Both measures taken together predicted response on week 5 with 73% sensitivity and 85% specificity with an odds ratio of 14.6. DISCUSSION: It is concluded that treatment with citalopram should be guided by symptom rating at baseline and on day 14 and serum concentration determination on day 7.

[Myelodysplastic syndromes. Epidemiology, molecular and morphological characteristics and risk stratification]. / Myelodysplastische Syndrome. Epidemiologie, molekulare und morphologische Merkmale, Risikostratifizierung.

Myelodysplastic syndromes (MDS) comprise a spectrum of clonal stem cell disorders which are currently defined according to the classification scheme of the revised 2008 WHO classification but which may be further refined in the future. The clinical presentation is often characterized by unexplained isolated or multiple peripheral blood cytopenias resulting in anemia, bleeding events or increased susceptibility to infections. The generally hypercellular, but rarely hypocellular and occasionally fibrotic bone marrow shows dysplastic features in ≥ 10 % of cells of at least one of the hematopoietic lineages. These features and enhanced apoptosis, stem cell senescence and immunologic dysregulation result in ineffective hematopoiesis. Diagnostics in MDS relies on complementary consideration of hematological, morphological and cytogenetic/molecular parameters. Methods include marrow and peripheral blood cytology, cytogenetics, fluorescence in situ hybridization (FISH), trephine bone marrow biopsy examination, immunophenotyping and the evaluation of molecular markers by established and new techniques. Mutations affecting growth factor receptors, cell cycle and apoptosis regulators, intracellular signaling, transcription factors, epigenetic regulation and the splicosome are involved in MDS pathogenesis and progression.

Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men.

BACKGROUND: Little is known about the effects of short-term caloric restriction (CR) and overfeeding (OF) on glucose homeostasis in healthy lean individuals. In addition, it remains unclear whether the effects of CR and OF are reversed by a complementary feeding period. METHODS: Ten healthy men participated in two cycles of controlled 7-day periods of CR and refeeding (RF; protocol A), and OF and CR (protocol B) at ±60% energy requirement. At baseline, insulin sensitivity (IS) was assessed by euglycemic clamp (M). Before and during each feeding cycle, fasting and oral glucose tolerance test-derived indices were used to estimate glucose tolerance, IS and glucose-stimulated insulin secretion. RESULTS: Clamp tests revealed normal IS at baseline (M-values 9.4±2.1 mg kg⁻¹ min⁻¹, coefficient of variation (CV)(inter) 22%). M-values were significantly correlated with indices of IS. In protocol A, CR-induced weight loss (-3.0±0.4 kg) was associated with an increase in fasting IS. Postprandial IS and glucose-stimulated insulin secretion remained unchanged, but glucose tolerance decreased. RF decreased fasting and postprandial IS at increased glucose-stimulated insulin secretion. In protocol B, OF significantly increased the body weight (+1.6±0.9 kg). Concomitantly, fasting and postprandial IS decreased at increased glucose-stimulated insulin secretion. Subsequent CR reversed these effects. Inter-individual variability in indices of glucose metabolism was high with coefficients of variation ranging from 9 to 59%. CONCLUSION: Significant changes in glucose metabolism are evident within 7-day periods of controlled OF and underfeeding. Although IS was impaired at the end of the CR-RF cycle, IS was normalized after the OF-CR cycle. At different feeding regimens, homeostatic responses of glucose metabolism were highly variable.

Different age-specific incidence and remission rates in pre-school and primary school suggest need for targeted obesity prevention in childhood.

BACKGROUND: School entry marks a tremendous change in the children's life style, which might well be relevant for the emergence of overweight. Previous studies suggested a dramatic increase in the prevalence of overweight during this age. OBJECTIVE: To compare the age-specific balance between the incidence and remission of overweight between pre-school and primary school age children. DESIGN: We combined the data of three studies that had been conducted within the setting of the compulsory school entry health examination in different parts of Germany: one covering retrospective cohort data from age 2 to school entry (n=5045), one prospective data from school entry to fourth grade (n=1235) and one comprising both (n=1194). We assessed the rates of incidence and remission of overweight and obesity from age 2 to school entry and from school entry to fourth grade. RESULTS: In pre-school age, the pooled incidence for overweight was 8.2% (95% confidence interval: 7.5, 8.9) compared with a remission rate of 62.6% (58.4, 66.7), yielding a prevalence at school entry of 10.7% (9.9, 11.5). In primary school age, the pooled incidence for overweight increased to 14.6% (13.1, 16.1), whereas the remission rate was reduced to 17.7% (13.8, 22.3), yielding a prevalence of 23.7% (22.0, 25.4) in fourth grade. A similar pattern was observed for obesity. CONCLUSIONS: While high remission rates balance incident overweight in pre-school years, the dramatic increase in the prevalence of overweight and obesity in primary school years reflects a higher incidence and even more a lower remission rate. Obesity prevention programs in primary school age are mandatory and need to address primary and secondary prevention elements.

The serotonin transporter promoter polymorphism (5-HTTLPR) affects the relation between antidepressant serum concentrations and effectiveness in major depression.

INTRODUCTION: Both the serotonin transporter promotor polymorphism (5-HTTLPR) and serum concentrations of SSRIs have been shown to affect response to SSRIs. Results, however, are inconsistent. The aim of this study was to investigate whether remission or response to SSRIs is influenced by an interaction of 5-HTTLPR and SSRI serum concentrations. METHODS: 49 patients with major depression and SSRI treatment were genotyped for the 5-HTTLPR locus including the rs25531. Drug serum concentrations and depression severity were measured weekly. RESULTS: Logistic regression analysis revealed a significant association between 5-HTTLPR, SSRI serum concentrations and response to treatment. A favourable treatment outcome correlated with SSRI serum concentration in 5-HTTLPR-L(A) allele carriers (r² = 34.3 %; p = 0.001), but not in S/L(G)-allele carriers (p = 0.31). DISCUSSION: In the group of L(A) allele carriers, those MDD patients with a high antidepressant serum concentrations responded better to treatment than patients with a low serum concentration. We conclude that the 5-HTTLPR might affect reponse to SRRI subject to serum concentrations. If replicated this might be a starting point for prospective clinical trials.

[Longitudinal data of the Kiel Obesity Prevention Study (KOPS)]. / Längsschnittdaten der Kieler Adipositas-Präventionsstudie (KOPS).

The Kiel Obesity Prevention Study (KOPS) has been performed since 1996. Examinations were performed at age 6, 10 and 14 years. In addition, birth weight as well as height and weight at age 2 years were collected retrospectively. For the study 4,997, 1,671 and 748 children were recruited at baseline (at age 6 years) as well as at 4 and 8-year follow-up, respectively. In this paper we will analyze and discuss (i) the important time period for preventive measures, (ii) effect sizes needed for successful interventions and (iii) suitable approaches for preventive measures. The main results were: (i) at age 6 years persistence of overweight was 69% while at younger ages persistence was 21% only. Thus, school entry was shown to be an important period for preventive measures. (ii) Interventions have to reduce energy balance by 140 kcal/day to prevent overweight (e.g. a reduction of energy intake). (iii) Prevention programs should involve the family and focus on increasing physical activity.

Neuropsychiatric symptoms and brain structural alterations in Fabry disease.

BACKGROUND: Neuropsychiatric symptoms (NPS), mainly cognitive deficits up to dementia and depressive syndromes have been described repeatedly in Fabry disease (FD). However, examinations regarding the pattern, extent, and frequency of the NPS in FD are still lacking. Moreover, the relationship between NPS and brain structural alterations in FD is unknown. The aim of this study was 1) to characterize NPS in a relatively large cohort of adult subjects with FD, and 2) to explore the association of cognitive performance and depressive syndromes with the FD-typical brain structural findings. METHODS: Twenty-five Fabry patients (age 36.5 ± 11.0) with mild to moderate disease involvement and 20 age, gender-, and education-matched healthy controls were extensively studied by neuropsychiatric assessment, structural magnetic resonance imaging, magnetic resonance angiography, and diffusion-tensor imaging. RESULTS: Patients with FD showed deficits only in the attention domain. Clinically relevant depressive syndromes were noted in 60% of the patients. The subgroup of patients with markedly elevated volumes of white matter lesions (not associated with actual stroke; n=7) showed slightly more learning and memory deficits, but no higher depression rate compared to less affected patients. CONCLUSIONS: Against the prevailing assumption, Fabry patients, even those with marked brain structural alterations, showed only mild cognitive deficits. The high frequency of depression in FD is likely to be related to the burden of this chronic multiorganic hereditary disease, but not to the FD-typical brain structural alterations. Longitudinal studies are necessary to clear, if the mild cognitive deficits in FD might precede clinically relevant cognitive decline.

AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate- and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint effort.