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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.

Ein 47-jahriger Diplom-Ingenieur, der seit uber 20 Jahren in der Produktentwicklung tatig ist, stellt sich in der Sprechstunde vor. Er berichtet, dass er seit Jahren einen wachsenden Druck am Arbeitsplatz verspurt und sich deswegen zunehmend erschopft, teilnahmslos und gleichgultig erlebt. Er habe eine gedruckte Stimmung, seine Interessen hatten deutlich nachgelassen, der Antrieb sei erheblich vermindert und er konne keine Freude mehr empfinden.

Ziel der Untersuchung: Systematische Erfassung des diagnostischen und therapeutischen Vorgehens bei psychiatrischen Notfallen in deutschen psychiatrischen Kliniken. Methodik: In einem Fragebogen wurden Versorgungsstrukturen der Kliniken und diagnostische und therapeutische Masnahmen bei psychiatrischen Notfallen erfasst. Ergebnisse: 42 % aller stationaren Aufnahmen waren Notaufnahmen. Als Notfallstandard wurden korperliche Untersuchung, Blutdruck- und Pulsmessung, Laborbestimmungen und Atemalkoholanalyse genannt. Die gebrauchlichsten Psychopharmaka fur Notfallsituationen waren Diazepam, Lorazepam, Haloperidol und Zuclopenthixol. Schlussfolgerung: Die Versorgung psychiatrischer Notfalle bedarf klarer Standards in Diagnostik und Therapie. Hierzu sind weitere, spezifischere Daten erforderlich.

Levamisole is an antihelminthic drug with immunomod- ulatory properties. Recent estimates suggest the majority of the cocaine in the United States is adulterated with levamisole. Le- vamisole-induced necrosis syndrome (LINES) is characterized by vasculitis, neutropenia, and purpura that progresses to skin necro- sis. Diagnosis relies on physical examination ndings and history of previous cocaine use. The purpose of this case series is to describe the pathophysiology, diagnosis, and management of LINES. The au- thors' institutional database was reviewed from 2008 to 2015, and they found 3 patients with LINES. Subsequent management and outcomes data are discussed. Patients had a variety of outcomes ranging from local wound care to necrosis and amputation of pha- langes. Patients with LINES can have a wide variety of outcomes; thus, this syndrome must be aggressively managed. Psychotherapy should also be utilized to help patients with further cocaine use. Levamisole-induced necrosis syndrome incidence is expected to in- crease, and all providers should be aware of this patient population.

Fur die Therapie schwerer psychischer Erkrankungen sind Psychopharmaka unverzichtbar. Da diese Substanzen haufig Nebenwirkungen aufweisen, ist eine kritische Indikationsstellung und Nutzen-Risiko-Bewertung erforderlich. Vor allem potenzielle Risiken, die eine Langzeitprognose negativ beeinflussen konnen, sollten rasch identifiziert und moglichst eliminiert werden.

BACKGROUND: Damage-control laparotomy (DCL) has revolutionized the surgery of injury. However, this has led to the dilemma of the nonclosable abdomen. Subsequently, there exists a subgroup of patients who after resuscitation and diuresis, remain nonclosable. Before the adoption of our open abdomen protocol (OAP) and use of transabdominal wall traction (TAWT), these patients required skin grafting and a planned ventral hernia. We hypothesize that our OAP and TAWT device, which use full abdominal wall thickness sutures to dynamically distribute midline traction, achieve an improved method of fascial reapproximation. METHODS: From 2008 to 2011, all DCL and decompressive laparotomy patients in our urban trauma center were managed by our OAP. Thirty two were noncloseable ‘‘domain loss abdomens’’ after achieving physiologic steady state and near dry weight. All patients received the TAWT device when near dry weight was achieved. Wound size, days to closure, days to TAWT, and TAWT to closure were tracked. RESULTS: During this 36-month period, OAP/TAWTwas applied to 32 patients. All patients demonstrated domain loss precluding fascial closure. Average wound size was 18.5-cm width by 30.5-cm length. Mean time DCL surgery to TAWTwas 9.5 days. At time of placement, TAWT decreased initial wound width by an average of 9.8 cm (51.4%). Patients returned to the operating room for tightening/washout an average of 2.2 times (excluding TAWT insertion and final closure operations). Mean time TAWT to closure was 8.7 days. Mean time from admission surgery to primary closure was 18.2 days. All patients achieved primary fascial closure using this method without components separation or biologic bridge operations. CONCLUSION: OAP/TAWT has revolutionized the way we manage ‘‘domain loss’’ open abdomen patients and has virtually eliminated the acceptance of planned ventral hernia. TAWT consistently recaptures lost domain, preserves the leading fascial edge, and eliminates the need for biologic bridges, components separation, or skin grafting. (J Trauma Acute Care Surg. 2013;74: 1486Y1492. Copyright * 2013 by Lippincott Williams & Wilkins)

International audience; BACKGROUND:Psychomotor agitation is associated with different psychiatric conditions and represents an important issue in psychiatry. Current recommendations on agitation in psychiatry are not univocal. Actually, an improper assessment and management may result in unnecessary coercive or sedative treatments. A thorough and balanced review plus an expert consensus can guide assessment and treatment decisions.METHODS:An expert task force iteratively developed consensus using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new, re-worded or re-rated items.RESULTS:Out of 2175 papers assessing psychomotor agitation, 124 were included in the review. Each component was assigned a level of evidence. Integrating the evidence and the experience of the task force members, a consensus was reached on 22 statements on this topic.CONCLUSIONS:Recommendations on the assessment of agitation emphasise the importance of identifying any possible medical cause. For its management, experts agreed in considering verbal de-escalation and environmental modification techniques as first choice, considering physical restraint as a last resort strategy. Regarding pharmacological treatment, the "ideal" medication should calm without over-sedate. Generally, oral or inhaled formulations should be preferred over i.m. routes in mildly agitated patients. Intravenous treatments should be avoided.

Background. Driving is an important activity of daily life and an integral part of mobility. However, impact of mental illness on road mobility is widely unexplored. Method. Driving status in 1497 psychiatric inpatients (PPs) and a clinical control group of 313 neurological inpatients (NPs) was investigated using a brief questionnaire. Results. 67% of PPs (89% NPs) reported to have a valid driver's licence and 77% of them (92% NPs) reported to regularly use their cars. Within driver's license holders, patients with organic mental disorder (32%), substance dependence (37%) and psychotic disorder (40%) had the lowest proportion of current drivers. Higher educational qualification (odds ratio [OR] from 2.978 to 17.036) and being married/partnered (OR 3.049) or divorced (OR 4.840) significantly advanced the probability of possession of a driving license. Predictive factors for driving cessation were being female, an older age, drawing a pension and having an organic mental disease or schizophrenic disorder. Conclusion. Mental disease has a negative impact on driving status and this is especially true for illnesses frequently being accompanied by distinct cognitive impairments. Factors predicting road mobility elucidate the strong relationship with psychosocial status indicating that recovery of driving competence should be an integral goal of treatment strategies.

Objective of this observational trial is to examine the effects of quetiapine in comparison with olanzapine and risperidone on clinical outcomes and quality of life in patients with schizophrenia and schizoaffective disorder in routine care. 374 adult persons with schizophrenia or schizoaffective disorder prescribed antipsychotic maintenance therapy with quetiapine, olanzapine, or risperidone at discharge from inpatient treatment were included. Clinical and psychosocial outcomes were assessed before discharge and at 6, 12, 18, and 24 months. Statistical analyses were conducted by mixed-effects regression models for longitudinal data. The propensity score method was used to control for selection bias. Patients discharged on olanzapine had significantly lower hospital readmissions than those receiving quetiapine or risperidone. The average chlorpromazine equivalent dose of quetiapine was higher than in patients treated with olanzapine or risperidone. No further significant differences between treatment groups were found. Quetiapine and risperidone are less effective in preventing the need for psychiatric inpatient care than olanzapine, and higher chlorpromazine equivalent doses of quetiapine are needed to obtain clinical effects similar to those of olanzapine and risperidone.

Aggression und Gewalt gegen Arzte kommen auch bei psychiatrischen Patienten und insbesondere unter Einfluss von Alkohol und/oder Drogen vor. Erregung und Aggression durchlaufen dabei definierte Stadien, die zur Gefahreneinschatzung hilfreich sein konnen. Der Arzt sollte versuchen, die Ursache fur Aggression und Gewalttatigkeit zu finden und sollte dabei aber zuerst auf seine eigene Sicherheit achten. Ist eine verbale Deeskalation nicht erfolgreich, kommt eine medikamentose Behandlung mit Benzodiazepinen oder Antipsychotika in Betracht.

Schennach-Wolff R, Obermeier M, Seemuller F, Jager M, Messer T, Laux G, Pfeiffer H, Naber D, Schmidt LG, Gaebel W, Klosterkotter J, Heuser I, Maier W, Lemke MR, Ruther E, Klingberg S, Gastpar M, Moller H-J, Riedel M. Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale. Objective: To examine depressive symptoms, their course during treatment, and influence on outcome. Method: Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to week 2, response as a 50% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from admission to discharge and remission according to the consensus criteria. Results: Thirty six per cent of the patients were depressed at admission, with 23% of them still being depressed at discharge. Depressed patients scored significantly higher on the PANSS negative and general psychopathology subscore, featured more impairments in subjective well-being (P

To describe the course of positive and negative symptoms during inpatient treatment and examine remission and response rates under routine clinical care conditions.Two hundred and eighty inpatients with schizophrenia (DSM-IV criteria) were assessed with the Positive and Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the symptom-severity component of the consensus criteria (Remission in Schizophrenia Working Group) as a rating of three or less in the relevant PANSS items at discharge, and response as a reduction of at least 20% in the PANSS total score from admission to discharge.The mean duration of inpatient treatment was 54.8 days. Of the total sample, 78.5% achieved the criteria for response and 44.6% those for remission. Mean PANSS total scores decreased from 72.4 at admission to 52.5 at discharge (p0.001). A reduction in PANSS total scores was found from visit to visit, up to week 8. The most pronounced decline was observed within the first two weeks of treatment.Response rates were comparable to those found in efficacy studies, and remission rates were slightly higher. This may be explained by differences in the selection and the treatment of patients. Nevertheless, the findings might indicate that a complex naturalistic treatment approach is beneficial in terms of effectiveness.

Background Purpose of the present study was to assess the attitude towards adherence at discharge and to verify its predictability using anamnestic and sociodemographic variables, factors influencing clinical treatment as well as the medical treatment applied. Methods Attitude towards adherence was evaluated in 369 inpatients with schizophrenic spectrum disorders within a naturalistic multicenter trial using the Compliance Rating Scale (CRS) by Kemp. Biweekly ratings of the PANSS, UKU and the Subjective Well-being under Neuroleptic Treatment Scale (SWN-K) were applied. Logistic regression and CART analyses were used to determine significant predictor variables for the attitude towards adherence at discharge. Results Sixty-seven percent of the patients were rated to have an attitude of active participation and moderate participation (=positive attitude towards adherence) and 33% of the patients to have an attitude of passive acceptance, occasional or permanent reluctance towards treatment as well as refusing treatment (=negative attitude towards adherence). A significant correlation was found between patients with a positive attitude towards adherence and course of all PANSS subscales. Statistical analyses revealed a reduction in PANSS general psychopathology subscore, employment status, greater illness insight and treatment with atypical antipsychotics to be significantly predictive for a positive attitude towards adherence at discharge. Conclusions The importance of an adequate antipsychotic treatment as a precondition for a favourable adherence attitude and the need to incorporate adherence-focused psychotherapy and psychoeducation into daily clinical practice are highlighted.

Depression is a common and often difficult-to-treat clinical condition with a high rate of patients showing insufficient treatment response and persistence of symptoms. We report the characteristics of a representative sample of depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Eight hundred and forty-two inpatients admitted to a psychiatric hospital for treatment of a major depressive episode, recurrent or bipolar depression were thoroughly characterized with respect to demographic factors, clinical history, and the degree of HPA-axis dysregulation evaluated by means of combined dex/CRH tests, and the predictive value of these factors for treatment outcome is investigated. 80.8% of patients responded to treatment (i.e., improvement in symptom severity of at least 50%) and 57.9% reached remission (i.e., near absence of residual depressive symptoms) at discharge after a mean treatment period of 11.8 weeks. Regression analysis identified early partial response (within 2 weeks) as the most important positive predictor for achieving remission. Previous ineffective treatment trials in the current episode and presence of a migration background are potent negative predictors for treatment outcome. In addition, remitters were characterized by a more pronounced normalization of an initially dysregulated HPA-axis. We could show that a large majority of inpatients suffering from depression benefits from antidepressant treatment during hospitalization. However, a considerable number of patients failed to achieve remission. We demonstrated that this subgroup can be characterized by a set of demographic, clinical and neuroendocrine variables allowing to predict unfavorable outcome at an early stage of treatment.

OBJECTIVE Various pharmacological strategies have been developed to treat such refractory depression, of which augmentation therapies are one of the most important. This article reviews both benefits and risks of all known augmentation therapies. METHODS The relevant literature was identified by means of a computerized MEDLINE research on the years 1990 - 2004 and scanning of review articles. RESULTS The efficacy of lithium augmentation is very well documented by a large number of controlled studies - lithium augmentation can therefore be recommended in depression refractory to antidepressant treatment. T3 augmentation is - in contrast to lithium augmentation - only a second-line strategy. There is an increasing number of augmentation therapies with atypical antipsychotics - its efficacy already supported by some well designed placebo controlled studies. Augmentation strategies with buspirone, modafinil and dopaminergic agents show good results in some case series and open studies, but there is a lack of doubleblind placebo controlled studies till now. Other augmentation therapies with stimulants, reserpine, pindolol, SAME and Yohimbine are very interesting clinical research strategies with rather little impact on clinical practice at the moment. CONCLUSIONS The distinct knowledge of available augmentation strategies may help to increase response - as well as remission rates in therapy resistant depression.

Polypharmazie in der Behandlung der Schizophrenie ist – wie haufig auch in der Behandlung anderer psychischer Storungen – das Resultat einer Therapieresistenz. Bis zu 70% der schizophrenen Patienten erreichen keine Vollremission, mindestens 30% der Betroffenen sprechen auf zwei oder mehr Monotherapien mit modernen Antipsychotika nicht an.

To analyze suicidal care episodes in emergency medical responses in Germany. Anonymized data from emergency care episodes in Ulm from 2004 to 2013 were analyzed retrospectively. 158 of 933 psychiatric emergencies (16 %) were suicide related, including 14 completed suicides, 25 care episodes with suicidal ideation, and 119 suicide attempts. Significantly more men than women completed suicide (χ²(2,N = 934) = 12.70, p = 0.02). 93 % of the total psychiatric emergencies received any medication at all, and only about 33 % were transported to a psychiatric hospital. Psychiatric treatment for suicidality in emergency medicine requires improvement to ensure that patients receive adequate therapy.

Current standards for the pharmacological treatment of schizophrenia favour antipsychotic monotherapy. Most atypical antipsychotics developed in recent years meet the statutory requirement of being at least as effective as Haloperidol. Nevertheless, pharmacoepidemiological data show an increase in polypharmacy. The importance of the studies is underlined by the fact that 40 - 50 % of schizophrenic inpatients and up to 90 % schizophrenic outpatients receive antipsychotic combination therapies. Treatment resistance, reduction of dose-related side effects caused by antipsychotic monotherapy or the effect on concomitant symptoms of schizophrenia, such as comorbid depression, might justify combination therapy or augmentation strategies. Apart from the high costs, polypharmacy is associated with reduced patient compliance and an increased risk of undesired pharmacological effects. Since polypharmacy is increasingly common further educational measures in psychopharmacology should be getting more attention. Due to the very small number of controlled studies that exist at present this report will focus on case reports of the most frequent as well as some of the lesser prescribed combination therapies. Finally, conclusions will be discussed in relation to therapy recommendations.

Background: Domain loss following damage-control laparotomy is a challenging problem many surgeons face. The authors recently developed trans–abdominal wall traction, which closed 100 percent of domain loss abdomens in the acute setting. They hypothesized that it can be used successfully in patients with chronic giant ventral defects. Methods: From 2008 to 2013, 44 patients with acute loss of domain and 10 with chronically giant ventral defects were enrolled in the open abdomen protocol with subsequent placement of the trans–abdominal wall traction device. Results: Patients’ average age in the acute and chronic groups was 28.2 and 35.3 years and average body mass index was 26.4 and 32.4 kg/m2, respectively. Ventral hernia size was reduced with the first trans–abdominal wall traction insertion from 610.5 cm2 to 274.6 cm2 in the acute setting and from 598 cm2 to 236.9 cm2 in the chronic setting. Average time from damage-control laparotomy to device insertion was 12.9 days in the acute group and more than 3 years in the chronic group. Lost domain was achieved with an average of less than 2.5 trans–abdominal wall traction tightenings, correlating to 9.2 and 8.2 days in the acute and chronic groups, respectively. Enterocutaneous fistula occurrence was 9 percent in the acute group and 0 percent in the chronic group. Conclusions: All patients were successfully closed after reestablishment of the lost domain. Trans–abdominal wall traction is an effective means of reestablishing abdominal domain and achieving primary abdominal wall closure in all patients with giant ventral defects, both acute and chronic. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Objectives: Reboxetine, a potent and selective noradrenaline reuptake inhibitor, has been approved for treatment of major depression. The aim of this study was to investigate the efficacy and tolerability of reboxetine in depressive outpatients undergoing treatment in routine clinical practice. Study design and methods: This post-marketing surveillance study was conducted to evaluate the therapeutic efficacy and tolerability of standard therapeutic doses of reboxetine in patients with depressive symptoms, particularly when administered in routine clinical practice. The 1835 patients (mean 54 years of age) evaluated showed demographic characteristics representative of the general depressive population. The majority of patients received the recommended dose of reboxetine 8 mg/day. Results: Measures of efficacy showed improvement in depressive symptoms with reboxetine therapy over the mean observational period of 9.6 weeks. Response to therapy, defined as Hamilton depression scale 21-item version score reduction of ≥50%, was reported in 83% of patients. The effects of reboxetine were rated by physicians as ‘good’ or ‘very good’ in 86% of patients at the last visit. The tolerability of reboxetine was rated by physicians as ‘good’ or ‘very good’ in 92% of patients at all evaluations. No adverse events that were possibly related to reboxetine therapy occurred in >1% of patients. Conclusion: The results of this study suggest that reboxetine is safe and well tolerated and may improve symptoms in depressive patients treated in routine clinical practice.

Objective. Temperament conventionally refers to stable behavioural and emotional reactions that appear early in life and are influenced in part by genetic constitution. Few studies compared temperamental traits in anxiety and mood disorders even though some authors suggested a clinical and neurobiological continuum between them. The aim of the study was to compare temperamental traits and psychopathological dimensions in subjects with DSM-IV diagnoses of mood and anxiety disorders. Methods. A total of 101 clinically stabilized consecutive outpatients (45 subjects with anxiety disorders and 56 with mood disorders diagnoses) were evaluated. The brief version of Temperament Evaluation of Memphis, Pisa, Paris and San Diego (briefTEMPS-M) and Symptom Checklist-90 (SCL-90) were used to assess temperamental traits and psychopathological dimensions, respectively. Results. No significant differences between anxiety disorders and mood disorders subjects for TEMPS-M or SCL-90 mean scores were observed. Different TEMPS-M scores differentially affect residual clinical symptoms. Conclusions. Our data represent an indirect indicator of possible common diathesis between the two different disorders. The temperament "paradigm" could explain part of the residual symptomatology. The evaluation of affective temperaments seems to add considerable clinical information to psychopathological and diagnostic descriptions.

Objective. The aim of the present 18-month retrospective study was to assess the association between a continuous long-term treatment with risperidone long-acting injectable (RLAI) of at least 12 months and in-patient care of patients suffering of schizophrenia or schizoaffective disorder. Furthermore we wanted to assess the cost-effectiveness of a long-term treatment with RLAI. Methods. In a mirror-image design, data of 119 patients with schizophrenia and schizoaffective disorder who were switched to RLAI treatment were analyzed retrospectively. Hospitalization rates, the duration of inpatient treatment and the overall treatment costs were assessed 12 and 18 months after switching to RLAI and compared to the equivalent time preceding the switch. Results. After 12 and 18 months of RLAI treatment, the mean reduction of inpatient care was 27.4 and 38.4 days per patient, respectively, compared to the equivalent time period prior to switching to RLAI (Wilcoxon P0.001). The overall savings in drug and institutional-care costs were 21.1 and 21.9%, respectively. Conclusions. Patients receiving RLAI for at least 12 months showed a reduction in inpatient days and lower overall treatment costs.

Im Bereich der adjuvanten Therapie des malignen Melanoms nimmt Interferon-alpha (IFN-α) eine wichtige Stellung ein. Unter den unerwunschten Nebenwirkungen spielen in der Langzeitbehandlung zunehmend psychische Veranderungen eine Rolle, insbesondere bei Therapieabbruchen. Bekannt sind Schlafstorungen, Unruhezustande, dauernde Mudigkeit, erhohte Erschopfbarkeit, zunehmende Reizbarkeit, sozialer Ruckzug und depressive Verstimmungen, die zumeist in den ersten drei Monaten der Behandlung entstehen. Aber auch schwerwiegende Nebenwirkungen wie delirante Zustande, schwere organische Depressionen, psychotische Episoden und organische Wesensanderungen konnen sich unter der Behandlung entwickeln und sogar zu Suizidversuchen fuhren. Anhand zweier Fallbeispiele werden Entstehungsmoglichkeiten suizidaler Syndrome unter der Therapie mit IFN-α verdeutlicht. Therapeutisch bieten sich je nach Schwere der Nebenwirkungen neben einer Dosisreduktion oder Behandlungsunterbrechung kurzfristig Benzodiazepine an. Gute Erfahrungen konnten bei leichten bis mittelschweren depressiven Syndromen mit Antidepressiva aus der Klasse der Serotonin-Wiederaufnahmehemmer gemacht werden, so das unter Umstanden eine Therapieunterbrechung vermieden werden kann. Bei schweren depressiven Syndromen oder organischen Wesensanderungen sollte primar die Behandlung mit IFN-α abgesetzt und bei Verdacht auf Suizidalitat eine stationar-psychiatrischer Behandlung erwogen werden.

OBJECTIVE Therapeutic drug monitoring (TDM) has been established at BKH Augsburg (psychiatric district hospital) since January 2001. According to Olanzapine product information the following illustration shows the evaluation (n = 216) of various parameters of the TDM requirements of Olanzapine. METHODS Items examined include "classification according to diagnoses", "reason for requirement", "severity of disease", "therapeutic effect" and "side-effects". In addition, serum concentration, daily dosage, clinical assessment (Brief Psychiatric Rating Scale), age, height and weight of patients will be presented. RESULTS Clearly sick patients, 52 % of them between 20 and 30 years old, were less compliant and achieved only a moderate therapeutic effect. CONCLUSIONS TDM is mainly assessed to control compliance. However, more specific and more personalized TDM would be more useful.