Transcranial direct current stimulation as an additional treatment to selective serotonin reuptake inhibitors in adults with major depressive disorder in Germany (DepressionDC): a triple-blind, randomised, sham-controlled, multicentre trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been proposed as a feasible treatment for major depressive disorder (MDD). However, meta-analytic evidence is heterogenous and data from multicentre trials are scarce. We aimed to assess the efficacy of tDCS versus sham stimulation as an additional treatment to a stable dose of selective serotonin reuptake inhibitors (SSRIs) in adults with MDD. METHODS: The DepressionDC trial was triple-blind, randomised, and sham-controlled and conducted at eight hospitals in Germany. Patients being treated at a participating hospital aged 18-65 years were eligible if they had a diagnosis of MDD, a score of at least 15 on the Hamilton Depression Rating Scale (21-item version), no response to at least one antidepressant trial in their current depressive episode, and treatment with an SSRI at a stable dose for at least 4 weeks before inclusion; the SSRI was continued at the same dose during stimulation. Patients were allocated (1:1) by fixed-blocked randomisation to receive either 30 min of 2 mA bifrontal tDCS every weekday for 4 weeks, then two tDCS sessions per week for 2 weeks, or sham stimulation at the same intervals. Randomisation was stratified by site and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score (ie, <31 or ≥31). Participants, raters, and operators were masked to treatment assignment. The primary outcome was change on the MADRS at week 6, analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one treatment session. The trial was registered with ClinicalTrials.gov (NCT02530164). FINDINGS: Between Jan 19, 2016, and June 15, 2020, 3601 individuals were assessed for eligibility. 160 patients were included and randomly assigned to receive either active tDCS (n=83) or sham tDCS (n=77). Six patients withdrew consent and four patients were found to have been wrongly included, so data from 150 patients were analysed (89 [59%] were female and 61 [41%] were male). No intergroup difference was found in mean improvement on the MADRS at week 6 between the active tDCS group (n=77; -8·2, SD 7·2) and the sham tDCS group (n=73; -8·0, 9·3; difference 0·3 [95% CI -2·4 to 2·9]). Significantly more participants had one or more mild adverse events in the active tDCS group (50 [60%] of 83) than in the sham tDCS group (33 [43%] of 77; p=0·028). INTERPRETATION: Active tDCS was not superior to sham stimulation during a 6-week period. Our trial does not support the efficacy of tDCS as an additional treatment to SSRIs in adults with MDD. FUNDING: German Federal Ministry of Education and Research.

Neurocognitive function as outcome and predictor for prefrontal transcranial direct current stimulation in major depressive disorder: an analysis from the DepressionDC trial.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex might beneficially influence neurocognitive dysfunctions associated with major depressive disorder (MDD). However, previous studies of neurocognitive effects of tDCS have been inconclusive. In the current study, we analyzed longitudinal, neurocognitive data from 101 participants of a randomized controlled multicenter trial (DepressionDC), investigating the efficacy of bifrontal tDCS (2 mA, 30 min/d, for 6 weeks) in patients with MDD and insufficient response to selective serotonin reuptake inhibitors (SSRI). We assessed whether active tDCS compared to sham tDCS elicited beneficial effects across the domains of memory span, working memory, selective attention, sustained attention, executive process, and processing speed, assessed with a validated, digital test battery. Additionally, we explored whether baseline cognitive performance, as a proxy of fronto-parietal-network functioning, predicts the antidepressant effects of active tDCS versus sham tDCS. We found no statistically significant group differences in the change of neurocognitive performance between active and sham tDCS. Furthermore, baseline cognitive performance did not predict the clinical response to tDCS. Our findings indicate no advantage in neurocognition due to active tDCS in MDD. Additional research is required to systematically investigate the effects of tDCS protocols on neurocognitive performance in patients with MDD.

Medical experience as an influencing parameter in emergency medical care for psychiatric emergencies: retrospective analysis of a multicenter survey.

BACKGROUND: Prehospital care of psychiatric patients often relies on the medical experience of prehospital emergency physicians (PHEPs). The psychiatrists (PSs) involved in the further treatment of psychiatric patients also often rely on their experience. Furthermore, the interaction between PHEPs and PSs is characterized by interaction problems and different approaches in the prehospital care of the psychiatric emergency. OBJECTIVES: To analyze the phenomenon of "medical experience" as a cause of possible interaction-related problems and assess its impact on the prehospital decision-making process between prehospital emergency physicians and psychiatrists. METHODS: The retrospective data analysis was conducted between November 2022 and March 2023. Medical experience was defined as follows, based on the demographic information collected in the questionnaires: For PHEPs, the period since obtaining the additional qualification in emergency medicine was defined as a surrogate marker of medical experience: (i) inexperienced: < 1 year, (ii) experienced: 1-5 years, (iii) very experienced: > 5 years. For PSs, age in years was used as a surrogate parameter of medical experience: (i) inexperienced: 25-35 years, (ii) experienced: 35-45 years, (iii) very experienced: > 45 years. RESULTS: Inexperienced PSs most frequently expressed anxiety about the psychiatric emergency referred by a PHEP (27.9%). Experienced PHEPs most frequently reported a lack of qualifications in handling the care of psychiatric emergencies (p = 0.002). Very experienced PHEPs were significantly more likely to have a referral refused by the acute psychiatric hospital if an inexperienced PS was on duty (p = 0.01). Experienced PHEPs apply an intravenous hypnotic significantly more often (almost 15%) than PSs of all experience levels (p = 0.001). In addition, very experienced PHEPs sought prehospital phone contact with acute psychiatry significantly more often (p = 0.01). CONCLUSION: PHEPs should be aware that the PS on duty may be inexperienced and that treating emergency patients may cause him/her anxiety. On the other hand, PHEPs should be receptive to feedback from PS who have identified a qualification deficiency in them. Jointly developed, individualized emergency plans could lead to better prehospital care for psychiatric emergency patients. Further training in the prehospital management of psychiatric disorders is needed to minimize the existing skills gap among PHEPs in the management of psychiatric disorders.

[Acute catatonia]. / Akute katatone Zustände.

BACKGROUND: Catatonia is an underdiagnosed psychomotor syndrome that can occur in the context of various mental and somatic diseases. Malignant catatonia is particularly relevant in the context of intensive medical care. Clear recommendations in guidelines are missing. OBJECTIVE: To present the current state of the diagnosis and treatment of catatonia, especially malignant catatonia. MATERIAL AND METHODS: The literature was evaluated with respect to acute catatonic conditions, with a special focus on the differential diagnosis, relevance to intensive medical care and treatment of catatonia. RESULTS: In psychiatric inpatients, catatonic syndromes are relatively frequent with a prevalence between 9% and 17%, and in neurological patients somewhat less frequent with a prevalence of 3.3%. There is a clear recommendation for pharmacological treatment with lorazepam. Additional electroconvulsive therapy (ECT) should be considered as early as possible, especially in cases not responding to benzodiazepines. Response rates to ECT have been shown to be 80-100%. In malignant catatonia, ECT should be performed immediately as an emergency indication. CONCLUSION: Several factors lead to the underdiagnosis of catatonia. It is problematic that even life-threatening malignant catatonia is often not recognized as such, although there is a mortality of about 50% if untreated. The best treatment outcome is achieved with a combination of benzodiazepines and ECT. The treatment of severe malignant catatonia represents an emergency indication for ECT.

Drug-Associated Liver Injury Related to Antipsychotics: Exploratory Analysis of Pharmacovigilance Data.

BACKGROUND: Drug-associated liver injury is one of the most common causes for acute liver failure and market withdrawal of approved drugs. In addition, the potential for hepatotoxicity related to specific substances has to be considered in psychopharmacotherapy. However, systematic evaluations of hepatotoxicity related to antipsychotics are limited. METHODS: We conducted an exploratory case/non-case study and evaluated pharmacovigilance data from VigiBase related to 30 antipsychotics marketed in the European Union. Reporting odds ratios were calculated for antipsychotics associated with the Standardized Medical Dictionary of Regulatory Activities queries "Drug-related hepatic disorders-comprehensive search" (DRHD-CS) and "Drug-related hepatic disorders-severe events only" (DRHD-SEO). RESULTS: We found several signals for drug-associated liver injury including signals for severe events: 17 of 30 antipsychotics were associated with DRHD-CS and 10 of 30 antipsychotics with DRHD-SEO. Amisulpride, fluphenazine, levomepromazine, loxapine, olanzapine, perazine, perphenazine, pipamperone, sulpiride, and thioridazine were associated with both, DRHD-CS and DRHD-SEO. No association with fatal outcomes was detected. CONCLUSIONS: Several common antipsychotics are associated with hepatotoxicity, partly also with severe hepatotoxicity. Our data do not allow to account for patient-related risk factors for drug-associated liver injury. This should be addressed in further studies.

Incidence of inpatient cases with mental disorders due to use of cannabinoids in Germany: a nationwide evaluation.

BACKGROUND: Quantitative (e.g. increasing recreational cannabinoid use) and qualitative (e.g. increasing availability and use of synthetic cannabinoids and cannabis preparations with increased tetrahydrocannabinol content) changes in cannabinoid use may be associated with changes in the prevalence of cannabinoid-related mental and behavioural disorders and, accordingly, changes in the need for medical care. We aimed to investigate if there are changes in the number of inpatient cases (ICs) due to cannabinoid-related disorders in Germany. METHODS: Data were obtained from the Federal Statistical Office of Germany (Destatis) and comprised type and number of hospital main diagnoses (according to ICD-10) of all ICs in Germany in the period 2000-18. Linear trend analysis of absolute and relative annual frequencies (AFs) of ICs with diagnoses related to the use of cannabinoids (DRUCs), and, as controls, alcohol-related psychiatric disorders and schizophrenia-spectrum disorders was performed. RESULTS: Absolute AFs of ICs with DRUCs increased statistically significantly (P<0.0001, trend analysis) in Germany between 2000 and 2018 and corresponding relative AFs increased considerably (4.8-fold increase when comparing 2000 and 2018). Specifically, absolute AFs of ICs with cannabinoid intoxications (P<0.0001), harmful use (P=0.0005), dependence syndrome (P< 0.0001), withdrawal state (P<0.0001), psychotic disorders (P< 0.0001) and residual and late-onset psychotic disorder (P<0.0001) statistically significantly increased. Absolute AFs of schizophrenia-spectrum disorders slightly, but statistically significantly decreased (P=0.008), and alcohol dependence did not statistically significantly change (P=0.844). CONCLUSIONS: Our evaluation demonstrates increasing numbers of ICs with mental and behavioural disorders due to use of cannabinoids in Germany and emphasizes the need for adequate prevention of such disorders.

Provision of Electroconvulsive Therapy During the COVID-19 Pandemic: A Survey Among Clinics in Germany, Austria, and Switzerland.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic has had a marked impact on psychiatry. Capacity reductions also affected electroconvulsive therapy (ECT), even though ECT is an essential rather than an elective procedure. We sent a survey to all 197 clinics in Germany, Austria, and Switzerland with an ECT service between March and May 2021 to provide an overview of the changes made to ECT services in these countries during the acute phase of the COVID-19 pandemic. More than a quarter of the clinics (27.0%) reported a temporary suspension of all ECT treatments, and 28.2% of the clinics reported reductions of up to 75%. Maintenance ECT was suspended in 46.7% of the clinics and reduced by up to 75% in 30.6% of the clinics. At the time of the survey, 40.8% of the clinics still reported lower numbers of ECT treatments compared with the prepandemic situation. Reasons for the reduced number of ECT treatments included patient safety and testing measures, personnel shortages in the anesthesiology departments, and limited availability of rooms. The COVID-19 pandemic had and continues to have a marked negative impact on the provision of ECT in clinics in Germany, Austria, and Switzerland. To avoid negative consequences for patients, ECT clinics should urgently take steps to provide ECT services without disruptions.

Emergency medical care of patients with psychiatric disorders - challenges and opportunities: Results of a multicenter survey.

BACKGROUND: Pre-clinical psychiatric emergencies are generally treated by emergency medical staff. The subsequent clinical treatment is often conditioned by interaction problems between emergency medical staff and psychiatric clinical staff. OBJECTIVES: To identify problems affecting interaction between emergency medical and psychiatric care of mentally ill patients and pinpoint aspects of optimized emergency care. METHODS: To shed light on the interaction problems an anonymous, questionnaire-based, nonrepresentative survey of 98 emergency physicians (EM) and 104 psychiatrists (PS) practicing in acute psychiatry was conducted between March 1, 2021 and October 1, 2021. RESULTS: The chi-square test for multiple response sets revealed consistently significant differences (p < 0.001) between EM and PS with respect to the questions analyzed. Approximately 36% of EM reported not to be adequately qualified to handle psychiatric emergencies (p = 0.0001), while around 50% of respondents were neutral in their assessment in how to deal with psychiatric emergencies. 80% of EM reported a negative interaction (rejection of patients) with PS when referring a psychiatric emergency patient to the acute psychiatric unit. The most common reasons for refusal were intoxication (EM: 78.8%, PS: 88.2%), emergency physician therapy (EM: 53.8%, PS: 63.5%), and not resident in the catchment area of the hospital (EM 68.8%, PS: 48.2%). In the casuistry presented, most respondents would choose "talk down" for de-escalation (EM: 92.1%, PS: 91.3%). With respect to drug therapy, benzodiazepine is the drug of choice (EM: 70.4%, PS: 78.8%). More EM would choose an intravenously (i.v.) or a Mucosal Atomization Device (MAD) administration as an alternative to oral medication (i.v.: EM: 38.8%, PS: 3.8%, p = 0.001, MAD: EM: 36.7%, PS: 10.6%, p = 0.006). Significantly more EM would seek phone contact with the acute psychiatric hospital (EM: 84.7%, PS: 52.9%, p = 0.0107). A psychiatric emergency plan was considered useful in this context by more than 90% of respondents. The need for further training for EM with regard to treating psychiatric clinical syndromes was considered important by all respondents. In particular, the topics of "psychogenic seizure," "intoxication," and "legal aspects of psychiatric emergencies" were considered important (Mann-Whitney U test, p < 0.001). CONCLUSION: The interaction-related problems identified in the emergency medical care of pre-clinical psychiatric patients relate to non-modifiable, structural problems, such as insufficient admission capacity and non-existent or inadequate monitoring capabilities in acute psychiatric hospitals. However, factors such as the education and training of EM and communication between EM and PS can be improved. Developing personalized emergency care plans for psychiatric patients could help to optimize their care.

[Mobbing Among Hospital Physicians]. / Mobbing unter Klinikärztinnen und -ärzten.

OBJECTIVES: Bullying in the workplace is considered an interpersonal stress factor. Occupational stress and mental health among physicians is increasingly becoming the focus of public attention. The extent to which mobbing plays a role in this has hardly been investigated yet. The aim of this study is to provide data on the prevalence of bullying among hospital physicians in Germany and possible correlations with occupational stress and mental health. METHODS: Within the framework of two cross-sectional studies, 692 hospital physicians in the field of psychiatry/psychotherapy (P/PT) and 667 hospital physicians in intensive care (IM) were interviewed at conferences. Standardized questionnaires on mobbing experience, occupational stress and mental health (single item from COPSOQ, BDI-II, ERI, MBI) were used. RESULTS: Bullying was experienced by 4.6% (n=61) of the respondents. IM and women physicians were more often affected (not significant) and correlations with occupational stress (ERI), overcommitment (OC), emotional exhaustion (MBI) and depression (BDI-II) were found. CONCLUSION: Our data on a large cohort of physicians in specialties with different exposure profiles show that a relevant proportion is affected by bullying and that bullying is related to the experience of occupational stress as well as mental health impairments. From this, implications for institutional and individual prevention and support services can be derived.

[Sulpiride induced dystonia in a patient with Tourette syndrome. A stroke-mimicking presentation]. / Sulpirid induzierte Dystonie bei einem Patienten mit Tourette-Syndrom - eine Schlaganfall ähnliche Präsentation.

We present a case of a 23-year-old male Caucasian patient admitted to the emergency department because of an acute onset of difficulty of articulation, weakness of the left arm, throat- and neck pain. An emergency CT & MRI of the brain showed no abnormalities. The Patient had started visiting a new neurologist three weeks before admission and received Sulpiride against Tourette syndrome (TS) in a rapid escalation manner over a short period. Sulpiride induced dystonia and other neurological symptoms that were clinically masked by dystonic and clonic tics of the known TS. 5 mg Biperiden (anticholinergic agent) was slowly injected intravenously under monitor condition. The Patient reported an immediate disappearance of articulation difficulties, left arm movement, and cervical and neck pain. After discontinuing Sulpiride the patient did not develop such attacks anymore and could be discharged the next day. This case shows the development of dystonia in correlation to the use of Sulpiride, which involved the cervical region, the laryngeal muscles, and the left upper extremity. Our case is of particular interest to neurologists and psychiatrists, because of their involvement in the treatment of TS. Therefore, young neurologists must be aware of such complications when thinking of differential diagnosis in movement disorders particularly in TS.

Arrhythmias related to antipsychotics and antidepressants: an analysis of the summaries of product characteristics of original products approved in Germany.

PURPOSE: Most psychiatric drugs, such as antidepressants (AD) and antipsychotics (AP), may cause cardiac adverse events (CAE). We used summaries of product characteristics (SmPC) for assessing the likelihood of AD and AP to cause CAE. METHODS: We identified all original medicinal products (OMP) of AD and AP approved in Germany. We searched for their SmPCs using the online services of PharmaNet.Bund, Gelbe liste®, Rote Liste®, Fachinfo-Service®, and via manufacturer contact. We extracted frequencies of reported CAE (QT prolongation, Torsade de Pointes tachycardia, and ventricular arrhythmia) and performed a risk assessment. RESULTS: We obtained the SmPCs of 24 AD and 26 AP identified as OMP. Comparably high reported frequencies regarding QT prolongation were found for Invega® (paliperidone), Serdolect® (sertindole) (≥ 1/100 and < 1/10), and Zoloft® (sertraline) (≥ 1/10.000 and < 1/1000); regarding Torsade de Pointes tachycardia were found for Serdolect® (≥ 1/1000 to < 1/100), Zoloft®, and Trevilor® (venlafaxine) (≥ 1/10.000 and < 1/1000); regarding ventricular tachycardia for Solian® (amisulpride), Xomolix® (droperidol), Zyprexa® (olanzapine), and Trevilor® (≥ 1/10.000 and < 1/1000). CONCLUSION: The risk and frequency of CAE, as reported in the SmPCs, varied significantly among substances and between groups. There are more reports for AP than AD. The AP with the most frequently reported CAE (QT prolongation and Torsade de Pointes tachycardia) was Serdolect®; for AD, Zoloft® (QT prolongation, Torsade de Pointes tachycardia) and Trevilor® (Torsade de Pointes tachycardia and ventricular tachycardia) carried a higher cardiac risk.

Factors related to age at depression onset: the role of SLC6A4 methylation, sex, exposure to stressful life events and personality in a sample of inpatients suffering from major depression.

BACKGROUND: An early onset of depression is associated with higher chronicity and disability, more stressful life events (SLEs), higher negative emotionality as described by the primary emotion SADNESS and more severe depressive symptomatology compared to depression onset later in life. Additionally, methylation of the serotonin transporter gene (SLC6A4) is associated with SLEs and depressive symptoms. METHODS: We investigated the relation of SLEs, SLC6A4 methylation in peripheral blood, the primary emotions SADNESS and SEEKING (measured by the Affective Neuroscience Personality Scales) as well as depressive symptom severity to age at depression onset in a sample of N = 146 inpatients suffering from major depression. RESULTS: Depressed women showed higher SADNESS (t (91.05) = - 3.17, p = 0.028, d = - 0.57) and higher SLC6A4 methylation (t (88.79) = - 2.95, p = 0.02, d = - 0.55) compared to men. There were associations between SLEs, primary emotions and depression severity, which partly differed between women and men. The Akaike information criterion (AIC) indicated the selection of a model including sex, SLEs, SEEKING and SADNESS for the prediction of age at depression onset. SLC6A4 methylation was not related to depression severity, age at depression onset or SLEs in the entire group, but positively related to depression severity in women. CONCLUSIONS: Taken together, we provide further evidence that age at depression onset is associated with SLEs, personality and depression severity. However, we found no associations between age at onset and SLC6A4 methylation. The joint investigation of variables originating in biology, psychology and psychiatry could make an important contribution to understanding the development of depressive disorders by elucidating potential subtypes of depression.

COVID-19: Factors associated with psychological distress, fear, and coping strategies among community members across 17 countries.

BACKGROUND: The current pandemic of COVID-19 impacted the psychological wellbeing of populations globally. OBJECTIVES: We aimed to examine the extent and identify factors associated with psychological distress, fear of COVID-19 and coping. METHODS: We conducted a cross-sectional study across 17 countries during Jun-2020 to Jan-2021. Levels of psychological distress (Kessler Psychological Distress Scale), fear of COVID-19 (Fear of COVID-19 Scale), and coping (Brief Resilient Coping Scale) were assessed. RESULTS: A total of 8,559 people participated; mean age (±SD) was 33(±13) years, 64% were females and 40% self-identified as frontline workers. More than two-thirds (69%) experienced moderate-to-very high levels of psychological distress, which was 46% in Thailand and 91% in Egypt. A quarter (24%) had high levels of fear of COVID-19, which was as low as 9% in Libya and as high as 38% in Bangladesh. More than half (57%) exhibited medium to high resilient coping; the lowest prevalence (3%) was reported in Australia and the highest (72%) in Syria. Being female (AOR 1.31 [95% CIs 1.09-1.57]), perceived distress due to change of employment status (1.56 [1.29-1.90]), comorbidity with mental health conditions (3.02 [1.20-7.60]) were associated with higher levels of psychological distress and fear. Doctors had higher psychological distress (1.43 [1.04-1.97]), but low levels of fear of COVID-19 (0.55 [0.41-0.76]); nurses had medium to high resilient coping (1.30 [1.03-1.65]). CONCLUSIONS: The extent of psychological distress, fear of COVID-19 and coping varied by country; however, we identified few higher risk groups who were more vulnerable than others. There is an urgent need to prioritise health and well-being of those people through well-designed intervention that may need to be tailored to meet country specific requirements.

Comparison of International Therapy Guidelines with Regard to the Treatment of Malignant Catatonia.

OBJECTIVE: Malignant catatonia (MC) is an extremely rare, life-threatening disorder. It is characterized by catatonic symptoms accompanied by autonomic instability, hyperthermia, and changes in laboratory values. In many cases, MC is not recognized as such. Evidence-based guidelines are essential to ensure quality of treatment, but what do current national and international guidelines recommend? METHOD: Online search for international guidelines from English-, French-, Italian-, and German-speaking countries whose medical care meets high standards addressing the treatment of MC. These were analyzed and compared regarding statements on MC, recommendations, and strength of scientific evidence. RESULTS: Fifteen of the identified guidelines were included. Only 5 of 15 comment on the treatment of MC. As for other rare diseases, no detailed recommendations are available. Suggested therapies are limited to benzodiazepines and electroconvulsive therapy. Levels of evidence and grades of recommendation are predominantly low. CONCLUSION: Many international guidelines do not mention MC. It is not possible to derive a clear algorithm for the treatment of MC from most current guidelines. A thorough update of most guidelines appears to be necessary. Lack of awareness and knowledge of MC among physicians and medical professionals might lead to inadequate or delayed care, worsened outcome, or death.

Treatment of the Neuroleptic Malignant Syndrome in International Therapy Guidelines: A Comparative Analysis.

INTRODUCTION: The neuroleptic malignant syndrome (NMS) is a potentially life-threatening condition associated to the use of antipsychotics. Since it requires rapid and efficient medical care, high-quality treatment guidelines should be available. In this article, we analyzed and compared different international therapy guidelines for the treatment of schizophrenia, in which NMS treatment recommendations might be contained. METHODS: We performed an Internet-based search for schizophrenia guidelines via the website of the respective medical society. Guidelines in English, French, Italian, and German from countries whose medical care meets high standards were selected for further analysis and comparison of the NMS treatment recommendations (if present), and their underlying evidence. RESULTS: The NMS is mentioned in 12 of 14 guidelines. Only 9 report concrete therapy recommendations (benzodiazepines/dantrolene/bromocriptine/amantadine/intensive care and/or electroconvulsive therapy (ECT)), however, with high heterogeneity. Only 5 guidelines included all possible drug therapy options and ECT, but with differing combination strategies, dosages, application forms, and combinability of options. The level of evidence of the different recommendations was estimated as low. DISCUSSION: One-third of the selected guidelines do not report any NMS therapy recommendations. Most guidelines mentioning the NMS do not provide therapy recommendations that include all relevant treatment options. The results show a very high heterogeneity, and the recommendations and statements are of low-evidence levels. The lack of knowledge about the NMS and its treatment may delay the onset of therapy, impair the quality of treatment, and lead to a worse outcome or death.

[Different number of contraindications between summaries of product characteristics (SmPC) of drugs with the same active ingredients - an analysis of data from SmPCs of neuropsychiatric drugs]. / Unterschiedliche Anzahl von Kontraindikationen zwischen Fachinformationen wirkstoffgleicher Arzneimittel ­ eine Analyse von Daten aus Fachinformationen von neuropsychiatrischen Arzneimitteln.

OBJECTIVE: In the case of prescriptions of pharmaceuticals in the context of the aut-idem-regulation the physician frequently does not know, which same-substance medication is dispensed in the pharmacy; the contemplable same-substance medications may differ in numerous features which raises questions regarding the obligation to give information and medical liability for medical malpractice. Currently, systematic evaluations regarding differences between summaries of product characteristics (SmPCs) of same-substance medications are missing. To determine size and type of those differences SmPCs of most (neuro)psychiatric drugs that are approved in Germany were evaluated regarding the number of listed contraindications (CI). METHODS: Basis for the selection of substances was the Anatomical Therapeutic Chemical (ATC) Classification System (group ATC N Nervous System). Substances that are approved in Germany for the treatment of mental disorders according to ICD-10 F were included. Brand-name medications and SmPCs were searched by means of further in- and exclusion criteria via the online services of PharmNet.Bund, Gelbe Liste, Rote Liste®/Fachinfo-Service® and communication with the manufacturer. RESULTS: N = 941 SmPCs (=116 substances) were evaluated. Considering only the group of SmPCs with > 1 brand-name medication (n = 78; 67.2 %) differences in the number of CIs were found in more than the half of substances (N = 43; 55.1 %). Considering indication groups most groups of SmPCs of same-substance medications with differences in the numbers of CIs were found in - considering only substances with > 1 brand-name medication - hypnotics and sedatives (77.8 %), anxiolytics (75.0 %), drugs for treatment of substance use disorders (66.7 %), antidepressants (61,9 %), anticonvulsant drugs and mood stabilizers (53.8 %), followed by antipsychotics (41.2 %), antidementia-drugs (20.0 %), and psychostimulants (0 %). Largest ranges regarding the number of CIs were found in the SmPCs of morphine (14), amitriptyline (8), chlorprothixene (6), lorazepam (6) and citalopram (4). CONCLUSION(S): In numerous (neuro-)psychopharmacologic substances differences exists between the SmPCs of the associated same-substance medications regarding the number of CIs. Due to the outstanding evaluation of content aspects of these differences and legal evaluation the relevance of this result for clinical practice is not yet clear.

Major depressive disorder: insight into candidate cerebrospinal fluid protein biomarkers from proteomics studies.

INTRODUCTION: Major Depressive Disorder (MDD) is the leading cause of global disability, and an increasing body of literature suggests different cerebrospinal fluid (CSF) proteins as biomarkers of MDD. The aim of this review is to summarize the suggested CSF biomarkers and to analyze the MDD proteomics studies of CSF and brain tissues for promising biomarker candidates. Areas covered: The review includes the human studies found by a PubMed search using the following terms: 'depression cerebrospinal fluid biomarker', 'major depression biomarker CSF', 'depression CSF biomarker', 'proteomics depression', 'proteomics biomarkers in depression', 'proteomics CSF biomarker in depression', and 'major depressive disorder CSF'. The literature analysis highlights promising biomarker candidates and demonstrates conflicting results on others. It reveals 42 differentially regulated proteins in MDD that were identified in more than one proteomics study. It discusses the diagnostic potential of the biomarker candidates and their association with the suggested pathologies. Expert commentary: One ultimate goal of finding biomarkers for MDD is to improve the diagnostic accuracy to achieve better treatment outcomes; due to the heterogeneous nature of MDD, using bio-signatures could be a good strategy to differentiate MDD from other neuropsychiatric disorders. Notably, further validation studies of the suggested biomarkers are still needed.

Sensitivity of Quantitative Signal Detection in Regards to Pharmacological Neuroenhancement.

Pharmacological neuroenhancement (PNE) is a form of abuse and has not yet been addressed by methods of pharmacovigilance. In the present study, we tested if quantitative signal detection may be sensitive in regards to PNE. We evaluated the risk of drug abuse and dependence (DAAD) related to substances that are known to be used for PNE and divided this group into agents with (methylphenidate) and without a known abuse potential outside the field of PNE (atomoxetine, modafinil, acetylcholine esterase inhibitors, and memantine). Reporting odds ratios (RORs) were calculated using a case/non-case approach based on global and country-specific drug safety data from the Uppsala Monitoring Centre (UMC). Both control substances (diazepam and lorazepam) and methylphenidate were statistically associated with DAAD in all datasets (except methylphenidate in Italy). Modafinil was associated with DAAD in the total dataset (ROR, 2.7 (95% confidence interval (CI), 2.2-3.3)), Germany (ROR, 4.6 (95% CI, 1.8-11.5)), and the USA (ROR, 2.0 (95% CI, 1.6-2.5)). Atomoxetine was associated with DAAD in the total dataset (ROR, 1.3 (95% CI, 1.2-1.5)) and in the UK (ROR, 3.3 (95% CI, 1.8-6.1)). Apart from memantine, which was associated with DAAD in Germany (ROR, 1.8 (95% CI, 1.0-3.2)), no other antidementia drug was associated with DAAD. Quantitative signal detection is suitable to detect agents with a risk for DAAD. Its sensitivity regarding PNE is limited, although atomoxetine and modafinil, which do not have a known abuse potential outside PNE, and no antidementia drugs, whose use in PNE is presumably low, were associated with DAAD in our analysis.

[Psychiatric Emergencies in the Preclinical Emergency Medicine Service in Ulm, Germany in 2000 and 2010, and Practical Consequences]. / Psychiatrische Notfälle im Notarzt- und Rettungsdienst in Ulm in den Jahren 2000 und 2010 und Konsequenzen für die Praxis.

Background Psychiatric emergencies (PE) in preclinical emergency medical services are about 5 - 10 % of all emergencies and represent often a source of difficulties in handling for the non-psychiatric professional helpers that deal with them. Studies informing about quantitative and qualitative changes of PEs in preclinical emergency medicine in Germany are scarce. Methods Therefore, we conducted a retrospective cross-sectional study of PE in a preclinical emergency medical service based on the protocols of the emergency ambulance of the Section for Emergency Medicine at the University Hospital Ulm comparing the years 2000 and 2010. Results We observed a significant increase of PEs from 8.8 % in the year 2000 (n = 285, from a total of n = 3227) to 10.3 % in 2010 (n = 454, from a total of n = 4425). In both years intoxications were the most common PE [2000: n = 116 (44.4 %); 2010: n = 171 (37.7 %)], followed by suicide-related behavior [2000: n = 59 (22.6 %); 2010: n = 78 (17.2 %)] and acute anxiety disorders [2000: n = 37 (13 %); 2010: n = 105 (23.1 %)]. The mentioned three conditions accounted for about 80 % of all PE. Most frequently PE occurred at the weekend and with the highest density in the evening and at night (18 - 24 h) in both years. Patients with PE were predominantly men, but the rate of women causing PE increased between 2000 and 2010. Discussion/Conclusion This study provides preliminary data on current trends in PEs in preclinical emergency medicine in Germany and has implications for improving the medical care provided.