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.

Harmonization of summaries of product characteristics (SmPCs) of drugs with the same active ingredients: an evaluation of SmPCs of the most frequently prescribed active substances.

PURPOSE: In aut-idem or generic substitution, discrepancies between summaries of product characteristics (SmPCs) referring to the same active substance (AS) may cause difficulties regarding informed consent and medical liability. The qualitative and quantitative characteristics of such discrepancies are insufficiently studied, impeding harmonization of same-substance SmPCs and compromising safe drug treatment. METHODS: SmPCs of the one hundred most frequently prescribed ASs in Germany were analyzed for discrepancies in the presentation of indications (Inds) and contraindications (CInds). Inclusion and exclusion criteria of drugs/SmPCs were chosen according to the standards of the aut-idem substitution in Germany. RESULTS: According to the study protocol, we identified 1486 drugs, of which 1426 SmPCs could be obtained. 41% respectively 65% of the ASs had same-substance SmPCs that differed from the respective reference SmPC in the number of listed Inds respectively CInds. The number of listed Inds/CInds varied considerably between same-substance SmPCs with maximum ranges in Inds of 7 in amoxicillin, and in CInds of 11 in lisinopril. Many ASs had large proportions (> 50%) of associated same-substance SmPCs that differed from the respective reference SmPC. A considerable proportion of ASs had same-substance SmPCs with formal and content-related differences other than the discrepancy in the number of Inds/CInds. CONCLUSION: This evaluation of same-substance SmPCs shows a clear lack of harmonization of same-substance SmPCs. Considering that generic substitution has become the rule and that physicians usually do not know which drug the patient receives in the pharmacy, these discrepancies raise several questions, that require a separate legal evaluation.

The Impact of Serotonin Transporter Binding Affinity on the Risk of Bleeding Related to Antidepressants.

PURPOSE/BACKGROUND: The alleged primary mechanism underlying bleeding events associated with antidepressants is inhibition of serotonin uptake in platelets resulting in reduced platelet aggregability and activity, and prolonged bleeding time. There is some evidence that a substance's degree of serotonin reuptake inhibition in terms of its binding affinity to the serotonin transporter (SERT) affects the magnitude of bleeding risk increase. METHODS/PROCEDURE: To test this hypothesis, we performed data mining in the worldwide largest pharmacovigilance database (VigiBase) and conducted pharmacodynamically informed quantitative signal detection. Reporting odds ratios related to the standardized Medical Dictionary of Regulatory Activities query term "haemorrhages" and 24 antidepressants were calculated, and SERT binding affinities (pKi) were obtained and correlated (Pearson correlation). FINDINGS/RESULTS: A strong and statistically significant correlation between substance-related reporting odds ratios and SERT binding affinities was found (r = 0.63; 95% confidence interval, 0.30-0.82; P = 0.00097). IMPLICATIONS/CONCLUSIONS: Our findings strengthen the hypothesis that inhibition of serotonin uptake contributes to the antidepressant-related bleeding risk and suggest an association between the degree of the SERT binding affinity and the bleeding risk. This supports the preferential use of antidepressants with low or no SERT binding affinity in depressed patients at risk of bleeding.

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.

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.

[Sleep disorders and impaired sleep as adverse drug reactions of psychotropic drugs: an evaluation of data of summaries of product characteristics]. / Schlafstörungen und Beeinträchtigungen des Schlafs als Nebenwirkungen von Psychopharmaka: eine Bewertung der Daten aus Fachinformationen.

OBJECTIVE: Psychopharmacotherapy is essential in the treatment of many mental disorders. Adverse drug reactions (ADR) have impact on compliance and tolerability. Sleep disorders or impaired sleep may occur as ADRs of psychopharmacotherapy. Sleep disorders are associated with an increased risk for physical and mental illness and may impair cognition, impulse control, emotion regulation and mood. Objective of the following study was the systematic presentation of type and risk of sleep disorders/impairments of sleep of frequently prescribed psychotropic drugs. METHODS: Psychotropic agents that are most frequently prescribed in Germany were identified by using the Arzneiverordnungs-Report 2016. Summaries of product characteristics (SmPC) of corresponding original products were analyzed regarding presence and frequency of sleep disorders/impairments of sleep according to the International Classification of Sleep Disorders 3 (ICSD-3). RESULTS: N = 64 SmPCs were analyzed. In most of the analyzed SmPCs, at least one sleep disorder (50/64; 78 %) was listed. At least one SmPC with a corresponding ADR was found in the categories insomnia (52 %), parasomnias (33 %), and sleep-related movement disorders (20 %); sleep-related breathing disorders (6 %) and central disorders of hypersomnolence (5 %) were rarely listed; circadian rhythm sleep-wake disorder was not found. The SmPCs of the four most frequently prescribed agents (citalopram > venlafaxine > mirtazapine > sertraline) listed insomnia as an ADR. Nearly all analysed hypnotics (except chloral hydrate) were associated with nightmares. CONCLUSION(S): Most of the psychotropic agents frequently prescribed in Germany may induce sleep disorders/impairments of sleep. The four most frequently prescribed agents were antidepressants and all of the corresponding SmPCs listed insomnia as a possible ADR. Sleep disorders should be taken seriously as possible ADRs of psychopharmacotherapy.

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.

[Update Opipramol]. / Update Opipramol.

Opipramol was developed in the 1960s as an antidepressant and has chemical similarities with tricyclic antidepressants. Pharmacodynamic properties with absent reuptake inhibition of serotonin and noradrenaline and agonism at sigma receptors distinguish opipramol from tricyclics. Furthermore, antidepressive effects are smaller than the anxiolytic ones. The mechanism of action of opipramol is currently not sufficiently understood. Agonistic effects at sigma receptors have been linked with therapeutic effects. Excessive hepatic metabolism (primarily via CYP2D6) should be considered, particularly in patients with impaired hepatic function and polypharmacy. The available clinical data suggest good tolerability and safety within the approved dose range. Mild disturbances of vigilance and anticholinergic adverse events are the predominant side effects. In Germany, opipramol is approved for the treatment of somatoform disorders and generalized anxiety disorder, and there is sufficient evidence for the efficacy of opipramol in these disorders. The agent is still prescribed very often in Germany, yet plays a minor role in the clinical as well as scientific setting. In view of the limited availability of (pharmacologic) treatment options for generalized anxiety disorder and particularly somatoform disorders, opipramol should be considered in the treatment of these entities.

[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.

Linking Annual Prescription Volume of Antidepressants to Corresponding Web Search Query Data: A Possible Proxy for Medical Prescription Behavior?

Persons using the Internet to retrieve medical information generate large amounts of health-related data, which are increasingly used in modern health sciences. We analyzed the relation between annual prescription volumes (APVs) of several antidepressants with marketing approval in Germany and corresponding web search query data generated in Google to test whether web search query volume may be a proxy for medical prescription practice. We obtained APVs of several antidepressants related to corresponding prescriptions at the expense of the statutory health insurance in Germany from 2004 to 2013. Web search query data generated in Germany and related to defined search terms (active substance or brand name) were obtained with Google Trends. We calculated correlations (Person's r) between the APVs of each substance and the respective annual "search share" values; coefficients of determination (R) were computed to determine the amount of variability shared by the 2 variables. Significant and strong correlations between substance-specific APVs and corresponding annual query volumes were found for each substance during the observational interval: agomelatine (r = 0.968, R = 0.932, P = 0.01), bupropion (r = 0.962, R = 0.925, P = 0.01), citalopram (r = 0.970, R = 0.941, P = 0.01), escitalopram (r = 0.824, R = 0.682, P = 0.01), fluoxetine (r = 0.885, R = 0.783, P = 0.01), paroxetine (r = 0.801, R = 0.641, P = 0.01), and sertraline (r = 0.880, R = 0.689, P = 0.01). Although the used data did not allow to perform an analysis with a higher temporal resolution (quarters, months), our results suggest that web search query volume may be a proxy for corresponding prescription behavior. However, further studies analyzing other pharmacologic agents and prescription data that facilitate an increased temporal resolution are needed to confirm this hypothesis.

Baseline brain perfusion and brain structure in patients with major depression: a multimodal magnetic resonance imaging study.

BACKGROUND: Abnormal regional cerebral blood flow (rCBF) and grey matter volume have been frequently reported in patients with major depressive disorder (MDD). However, it is unclear to what extent structural and functional change co-occurs in patients with MDD and whether markers of neural activity, such as rCBF, can be predicted by structural change. METHODS: Using MRI, we investigated resting-state rCBF and brain structure in patients with MDD and healthy controls between July 2008 and January 2013. We acquired perfusion images obtained with continuous arterial spin labelling, used voxel-based morphometry to assess grey matter volume and integrated biological parametric mapping analyses to investigate the impact of brain atrophy on rCBF. RESULTS: We included 43 patients and 29 controls in our study. Frontotemporal grey matter volume was reduced in patients compared with controls. In patients, rCBF was reduced in the anterior cingulate and bilateral parahippocampal areas and increased in frontoparietal and striatal regions. These abnormalities were confirmed by analyses with brain volume as a covariate. In patients with MDD there were significant negative correlations between the extent of depressive symptoms and bilateral parahippocampal rCBF. We found a positive correlation between depressive symptoms and rCBF for right middle frontal cortical blood flow. LIMITATIONS: Medication use in patients has to be considered as a limitation of our study. CONCLUSION: Our data suggest that while changes of cerebral blood flow and brain volume co-occur in patients with MDD, structural change is not sufficient to explain altered neural activity in patients at rest. Abnormal brain structure and function in patients with MDD appear to reflect distinct levels of neuropathology.

Safety of electroconvulsive therapy in the presence of cranial metallic objects.

OBJECTIVES: Little is known regarding the safety of electroconvulsive therapy (ECT) in the presence of cranial metallic objects (cMO) such as medical devices or metallic foreign bodies. The presence of cMO raises 3 theoretical concerns toward the safety of ECT: (1) cMO may significantly alter the ECT-induced electric field distribution in the brain regarding field strength and focality, (2) vascular complications at the location of the cMO due to the ECT-induced hyperdynamic state may occur, and (3) possible development of a prolonged seizure/status epilepticus during ECT as a consequence of a device-induced symptomatic epilepsy. In the light of missing systematic approaches, we intended to assess the safety of ECT in the presence of cMO with particular regard to the concerns as specified previously. METHODS: A systematic review of previously published cases of ECT in patients with cMO was conducted. RESULTS: We identified 23 publications reporting 24 cases of ECT in the presence of cMO (cerebral clipping systems, 8 cases; cerebral coils, 2 cases; deep brain stimulator, 4 cases; osteosynthesis materials or other metallic medical devices, 7 cases; foreign bodies, 3 cases). Modified placement of ECT-electrodes was reported in 10 cases (42%). No ECT-related complications with regard to the proposed theoretical concerns were reported. CONCLUSIONS: The absence of cMO-related complications during ECT in the reported cases implies that cMO might not represent an absolute contraindication for the performance of ECT. However, the indication for ECT should be put in place thoroughly in patients with cMO. Further research is necessary for an adequate safety assessment.

Cerebrospinal fluid biomarker candidates of schizophrenia: where do we stand?

Here, we review the cerebrospinal fluid (CSF) candidate markers with regard to their clinical relevance as potential surrogates for disease activity, prognosis assessment, and predictors of treatment response. We searched different online databases such as MEDLINE and EMBASE for studies on schizophrenia and CSF. Initial studies on cerebrospinal fluid in patients with schizophrenia revealed increased brain-blood barrier permeability with elevated total protein content, increased CSF-to-serum ratio for albumin, and intrathecal production of immunoglobulins in subgroups of patients. Analyses of metabolites in CSF suggest alterations within glutamatergic neurotransmission as well as monoamine and cannabinoid metabolism. Decreased levels of brain-derived neurotrophic factor and nerve growth factor in CSF of first-episode patients with schizophrenia reported in recent studies point to a dysregulation of neuroprotective and neurodevelopmental processes. Still, these findings must be considered as non-specific. A more profound characterization of the particular psychopathological profiles, the investigation of patients in the prodromal phase or within the first episode of schizophrenia promoting longitudinal investigations, implementation of different approaches of proteomics, and rigorous adherence to standard procedures based on international CSF guidelines are necessary to improve the quality of CSF studies in schizophrenia, paving the way for identification of syndrome-specific biomarker candidates.

"Krokodil":revival of an old drug with new problems.

In order to summarize current knowledge about the drug "Krokodil" a systematic review including a literature search of the databases PubMed, Embase, Scopus, and Google was conducted in December 2011. According to information acquired, "Krokodil" is a mixture of several substances and was first reported to have been used in Russia in 2003. The core agent of "Krokodil" is desomorphine, an opioid-analogue that can be easily and cheaply manufactured by oneself. Self-production results in a contaminated suspension that is injected intravenously. Due to its pharmacologic features, desomorphine shows a high potential to cause dependence. Against the background of first possible cases of "Krokodil" use in Western Europe, it appears advisable to provide information regarding the fatal consequences of "Krokodil."

Psychological Distress, Fear and Coping Strategies During the Second and Third Waves of the COVID-19 Pandemic in Southern Germany.

Background: The COVID-19 pandemic has imposed enormous psychological discomfort and fear across the globe, including Germany. Objectives: To assess the levels of COVID-19 associated psychological distress and fear amongst Southern German population, and to identify their coping strategies. Methods: A cross-sectional survey using an online questionnaire was conducted in healthcare and community settings in the region of Ulm, Southern Germany. Assessment inventories were the Kessler Psychological Distress Scale (K-10), the Brief Resilient Coping Scale (BRCS), and the Fear of COVID-19 Scale (FCV-19S), which were valid and reliable tools. Results: A total of 474 Individuals participated in the study. The mean age was 33.6 years, and 327 (69%) were females. Most participants (n = 381, 80.4%) had high levels of psychological distress, whereas only 5.1% had high levels of fear, and two-thirds of participants showed higher levels of coping. Moderate to very high levels of psychological distress were associated with being female, living alone, distress due to employment changes, experiencing financial impact, having multiple co-morbidities, being a smoker, increased alcohol use over the previous 6 months, contact with COVID-19 cases and healthcare providers for COVID-19-related stress. Individuals who were ≥60 years, lived with non-family members, had co-morbidities and visited a healthcare provider had higher levels of fear. Higher levels of education and income showed better coping amongst participants. Conclusion: Psychological distress was very high during the COVID-19 pandemic in Germany and associated with low levels of coping. This study identified vulnerable groups of people, who should be given priorities for addressing their health and wellbeing in future crisis periods.

Exploring the affective component of pain perception during aversive stimulation in borderline personality disorder.

In a pilot study, affective components of pain were assessed using repetitive peripheral magnetic stimulation (rPMS) in patients with borderline personality disorder and healthy controls. Significant differences in pain thresholds and in affective components of pain between both groups were found. rPMS was well tolerated and suitable for assessing pain.