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.

The impact of a digital guideline version on schizophrenia guideline knowledge: results from a multicenter cluster-randomized controlled trial.

BACKGROUND: Clinical practice guidelines are crucial for enhancing healthcare quality and patient outcomes. Yet, their implementation remains inconsistent across various professions and disciplines. Previous findings on the implementation of the German guideline for schizophrenia (2019) revealed low adherence rates among healthcare professionals. Barriers to guideline adherence are multifaceted, influenced by individual, contextual, and guideline-related factors. This study aims to investigate the effectiveness of a digital guideline version compared to print/PDF formats in enhancing guideline adherence. METHODS: A multicenter, cluster-randomized controlled trial was conducted in South Bavaria, Germany, involving psychologists and physicians. Participants were divided into two groups: implementation of the guideline using a digital online version via the MAGICapp platform and the other using the traditional print/PDF version. The study included a baseline assessment and a post-intervention assessment following a 6-month intervention phase. The primary outcome was guideline knowledge, which was assessed using a guideline knowledge questionnaire. RESULTS: The study included 217 participants at baseline and 120 at post-intervention. Both groups showed significant improvements in guideline knowledge; however, no notable difference was found between both study groups regarding guideline knowledge at either time points. At baseline, 43.6% in the control group (CG) and 52.5% of the interventional group (IG) met the criterion. There was no significant difference in the primary outcome between the two groups at either time point (T0: Chi2(1) = 1.65, p = 0.199, T1: Chi2(1) = 0.34, p = 0.561). At post-intervention, both groups improved, with 58.2% in the CG and 63.5% in the IG meeting this criterion. CONCLUSIONS: While the study did not include a control group without any implementation strategy, the overall improvement in guideline knowledge following an implementation strategy, independent of the format, was confirmed. The digital guideline version, while not superior in enhancing knowledge, showed potential benefits in shared decision-making skills. However, familiarity with traditional formats and various barriers to digital application may have influenced these results. The study highlights the importance of tailored implementation strategies, especially for younger healthcare providers. TRIAL REGISTRATION: https://drks.de/search/de/trial/DRKS00028895.

Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders - An individual patient data meta-analysis.

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorders(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI -0.55-0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05-0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17-0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptoms severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies.

Vaccination and clozapine use: a systematic review and an analysis of the VAERS database.

In the context of COVID-19 concerns related to the potential interactions between clozapine and vaccination arose. With the ultimate goal of deriving recommendations for clinical practice, we systematically reviewed the current evidence regarding altered vaccine effectiveness in clozapine-treated patients and safety aspects of vaccination, such as haematological changes and the impact of vaccines on clozapine blood levels, in clozapine-treated patients. A systematic PRISMA-conform literature search of four databases (PubMed, PsycINFO, EMBASE and Cochrane Library) complemented by a case-by-case analysis of the Vaccine Adverse Event Reporting System (VAERS) database was performed. We then systematically appraised the joint evidence and tried to derive recommendations for clinical practice. 14 records were included in this analysis. These records consisted of 5 original articles and 9 case reports. Among the original articles, two studies provided data on the association between clozapine use and antibody responses to vaccination, both indicating that clozapine use in schizophrenia may be associated with reduced levels of immunoglobulins. Additionally, three studies examined vaccine safety in clozapine-treated patients, with no clinically significant adverse effects directly attributable to the interplay between vaccinations and clozapine. VAERS Analysis encompassed 137 reports and showed no consistent evidence of an increased risk for clozapine blood level increases or adverse events. We found no evidence indicating that clozapine impairs the effectiveness of vaccines. Moreover, no serious safety concerns seem to apply when patients on clozapine are receiving vaccines. However, it is crucial to acknowledge that data on the interaction between clozapine and vaccines remain limited.

Polygenetic risk scores and phenotypic constellations of obsessive-compulsive disorder in clozapine-treated schizophrenia.

Obsessive-compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clozapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive-compulsive disorder (OCD) in this subgroup and find possible correlations with different phenotypes. Additionally, this is the first study to examine polygenetic risk scores (PRS) in individuals with SCZ and OCS. A multicenter cohort of 91 individuals with SCZ who were treated with CLZ was recruited and clinically and genetically assessed. Symptom severity was examined using the Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI), the Calgary Depression Scale for Schizophrenia (CDSS), Global Assessment of Functioning Scale (GAF) and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Participants were divided into subgroups based on phenotypic OCS or OCD using Y-BOCS scores. Genomic-wide data were generated, and PRS analyses were performed to evaluate the association between either phenotypic OCD or OCS severity and genotype-predicted predisposition for OCD, SCZ, cross-disorder, and CLZ/norclozapine (NorCLZ) ratio, CLZ metabolism and NorCLZ metabolism. OCS and OCD were frequent comorbidities in our sample of CLZ-treated SCZ individuals, with a prevalence of 39.6% and 27.5%, respectively. Furthermore, the Y-BOCS total score correlated positively with the duration of CLZ treatment in years (r = 0.28; p = 0.008) and the PANSS general psychopathology subscale score (r = 0.23; p = 0.028). A significant correlation was found between OCD occurrence and PRS for CLZ metabolism. We found no correlation between OCS severity and PRS for CLZ metabolism. We found no correlation for either OCD or OCS and PRS for OCD, cross-disorder, SCZ, CLZ/NorCLZ ratio or NorCLZ metabolism. Our study was able to replicate previous findings on clinical characteristics of CLZ-treated SCZ individuals. OCS is a frequent comorbidity in this cohort and is correlated with CLZ treatment duration in years and PANSS general psychopathology subscale score. We found a correlation between OCD and PRS for CLZ metabolism, which should be interpreted as incidental for now. Future research is necessary to replicate significant findings and to assess possible genetic predisposition of CLZ-treated individuals with SCZ to OCS/OCD. Limitations attributed to the small sample size or the inclusion of subjects on co-medication must be considered. If the association between OCD and PRS for CLZ metabolism can be replicated, it should be further evaluated if CYP1A2 alteration, respectively lower CLZ plasma level, is relevant for OCD development.

Intermittent theta burst stimulation in adolescents and young adults with depressive disorders: protocol of a randomized, sham-controlled study with a sequential Bayesian design for adaptive trials.

Intermittent theta burst stimulation (iTBS), a variant of repetitive transcranial magnetic stimulation (rTMS), is an established treatment for adults with major depressive disorder (MDD). Due to its favorable safety profile, iTBS is also a promising early intervention in the transition phase from adolescence to early adulthood, but this has not been systematically investigated to date. Thus, the EARLY-BURST trial investigates the efficacy and safety of iTBS over the left dorsolateral prefrontal cortex (lDLPFC) in treatment-seeking young patients (age 16-26 years) with depressive disorders (i.e. major depressive disorder, persistent depressive disorder, bipolar depression), allowing for relevant co-morbidities. Participants have not received antidepressant or antipsychotic medication during the last 12 months except for short-term (< 2 weeks) on-demand medication. The trial will employ a novel sequential Bayesian, randomized, double-blind, parallel-group, sham-controlled design. Up to 90 patients at two clinical sites (Munich, Augsburg) will be randomized 1:1 to the treatment groups, with sequential analyses starting after 26 patients in each group completed the treatment. The primary outcome will be the difference in depression severity at week 6 (post-treatment visit) between active iTBS and sham iTBS, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). The trial is planned to be expanded towards a three-arm leapfrog design, contingent on securing additional funding. Thus, in addition to potentially providing evidence of iTBS's efficacy in adolescents and young adults with depressive disorders, the EARLY-BURST trial aims at setting the stage for subsequent platform trials in this dynamic research field, where novel adaptive study designs are required to meet the need for rapidly testing promising new vs established rTMS protocols.Trial registration: DRKS00033313.

Predictors of adherence to exercise interventions in people with schizophrenia.

Exercise interventions are nowadays considered as effective add-on treatments in people with schizophrenia but are usually associated with high dropout rates. Therefore, the present study investigated potential predictors of adherence from a large multicenter study, encompassing two types of exercise training, conducted over a 6-month period with individuals with schizophrenia. First, we examined the role of multiple participants' characteristics, including levels of functioning, symptom severity, cognitive performance, quality of life, and physical fitness. Second, we used K-means clustering to identify clinical subgroups of participants that potentially exhibited superior adherence. Last, we explored if adherence could be predicted on the individual level using Random Forest, Logistic Regression, and Ridge Regression. We found that individuals with higher levels of functioning at baseline were more likely to adhere to the exercise interventions, while other factors such as symptom severity, cognitive performance, quality of life or physical fitness seemed to be less influential. Accordingly, the high-functioning group with low symptoms exhibited a greater likelihood of adhering to the interventions compared to the severely ill group. Despite incorporating various algorithms, it was not possible to predict adherence at the individual level. These findings add to the understanding of the factors that influence adherence to exercise interventions. They underscore the predictive importance of daily life functioning while indicating a lack of association between symptom severity and adherence. Future research should focus on developing targeted strategies to improve adherence, particularly for people with schizophrenia who suffer from impairments in daily functioning.Clinical trials registration The study of this manuscript which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112, https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1 ) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804.

Association of Four Medication Classes and Non-suicidal Self-injury in Adolescents with Affective Disorders - A Retrospective Chart Review.

BACKGROUND: Non-suicidal self-injury (NSSI) behaviour is frequently observed in children and adolescents with psychiatric conditions. Affected individuals are regularly treated with psychotropic drugs, although the impact of these agents on NSSI behaviour remains elusive. METHODS: We performed a retrospective chart review from clinical routine data in a large cohort (N=1140) of adolescent inpatients with primary affective and non-affective psychiatric disorders according to ICD-10 (mean age=15.3±1.3 years; 72.6% female). Four separate mixed regression models compared the frequency of NSSI between treatment periods without any medication and four medication categories (benzodiazepines, selective serotonin reuptake inhibitors (SSRIs), high- and low-potency antipsychotics). RESULTS: In those individuals with affective disorders as the primary diagnosis, periods without medication were associated with significantly lower NSSI/day compared to all four other medication conditions (benzodiazepines p<10-8, antidepressants/SSRIs p=0.0004, high-potency antipsychotics p=0.0009, low-potency antipsychotics p<10 -4). In individuals with a primary diagnosis other than an affective disorder, NSSI was significantly lower during the period without medication compared to the treatment periods with benzodiazepines (p=0.005) and antidepressants/SSRIs (p=0.01). However, NSSI rates in the no-medication condition were comparable to NSSI rates under high-potency (p=0.89) and low-potency antipsychotics (p=0.53). CONCLUSIONS: The occurrence of NSSI correlates with the treatment with a psychotropic drug in children and adolescents with psychiatric disorders. Due to the retrospective design, it remains elusive to what extent psychotropic drugs might alter the frequency of NSSI in adolescents or if NSSI might indicate a transdiagnostic feature of more pronounced disease severity.

The influence of marathon running on resting-state EEG activity: a longitudinal observational study.

Physical activity (PA) has positive effects on various health aspects and neuronal functions, including neuronal plasticity. Exceeding a certain exercise frequency and duration has been associated with negative effects. Our study investigated the effects of excessive PA with a marathon run (MA) and regular PA (training and recovery phases) on electrocortical activity, as measured by electroencephalography (EEG). Thirty healthy marathon runners (26 male, 45 ± 9 yrs) were enrolled in the study. Four resting-state 32 channel EEG recordings were conducted: 12-8 weeks before MA (T-1), 14-4 days prior to MA (T0), 1-6 days after (T2), and 13-15 weeks after MA (T3). Power spectrum analyses were conducted using standardized Low-Resolution Electromagnetic Tomography (sLORETA) and included the following frequency bands: delta (1.5-6 Hz), theta (6.5-8.0 Hz), alpha1 (8.5-10 Hz), alpha2 (10.5-12.0 Hz), beta1 (12.5-18.0 Hz), beta2 (18.5-21.0 Hz), beta3 (21.5-30.0 Hz), and total power (1.5-30 Hz). Statistical nonparametric mapping showed reduced power both in the alpha-2 (log-F ratio = - 0.705, threshold log-F ratio = ± 0.685, p < 0.05) and in the delta frequency band (log-F ratio = -0.699, threshold log-F ratio = ± 0.685, p < 0.05) in frontal cortical areas after MA (T2 vs. T0). These effects diminished at long-term follow-up (T3). The results can be interpreted as correlates for subacute neuroplasticity induced by strenuous and prolonged PA. Although previous studies reported an increase in alpha frequency during and directly postexercise, the adverse observation a few days after exercise cessation suggests counterregulatory mechanisms, whose complex origin can be suspected in subcortical circuits, changes in neurotransmitter systems and modulation of affectivity.

Culturally sensitive stepped care for adolescent refugees: efficacy and cost-utility of a multicentric randomized controlled trial.

Adolescent refugees and asylum seekers (ARAS) are highly vulnerable to mental health problems. Stepped care models (SCM) and culturally sensitive therapies offer promising treatment approaches to effectively provide necessary medical and psychological support. To our knowledge, we were the first to investigate whether a culturally sensitive SCM will reduce symptoms of depression and PTSD in ARAS more effectively and efficiently than treatment as usual (TAU). We conducted a multicentric, randomized, controlled and rater-blinded trial across Germany with ARAS between the ages of 14 to 21 years. Participants (N = 158) were stratified by their level of depressive symptom severity and then equally randomized to either SCM or TAU. Depending on their severity level, SCM participants were allocated to tailored interventions. Symptom changes were assessed for depression (PHQ) and PTSD (CATS) at four time points, with the primary end point at post-intervention after 12 weeks. Based on an intention-to-treat sample, we used a linear mixed model approach for the main statistical analyses. Further evaluations included cost-utility analyses, sensitivity analyses, follow-up-analyses, response and remission rates and subgroup analysis. We found a significant reduction of PHQ (d = 0.52) and CATS (d = 0.27) scores in both groups. However, there was no significant difference between SCM and TAU. Cost-utility analyses indicated that SCM generated greater cost-utility when measured as quality-adjusted life years compared to TAU. Subgroup analysis revealed different effects for the SCM interventions depending on the outcome measure. Although culturally sensitive, SCMs did not prove to be more effective in symptom change and represent a more cost-effective treatment alternative for mentally burdened ARAS. Our research contributes to the optimization of clinical productivity and the improvement of therapeutic care for ARAS. Disorder-specific interventions should be further investigated.

[Management of treatment resistance-Treatment-resistant schizophrenia]. / Management von Therapieresistenzen ­ therapieresistente Schizophrenie.

Despite a very high prevalence and substantial impairments among affected individuals, treatment-resistant schizophrenia (TRS) has not been sufficiently researched in clinical research in the field of psychiatric disorders and the pathophysiology is still poorly understood. A better clinical and pathophysiological understanding of this heterogeneous and severely affected population of people with persistent symptoms in different domains is necessary in order not only to be able to intervene early but also to develop novel therapeutic strategies or individualized treatment approaches. This review article presents the state of the art criteria of the pharmacological TRS, neurobiological disease models and predictive factors for TRS as well as the phenomenon of pseudo-treatment resistance and the clinical management of TRS. In the future, not only the use of operationalized criteria and definitions of TRS in longitudinal studies and randomized-controlled trials (RCTs) are paramount, but also the observation of trajectories with the integration of multimodal longitudinal phenotyping and the longitudinal collection of clinical routine data in academic research, which will be possible in the newly created German Center for Mental Health (DZPG).

[Deprescribing in DGPPN S3 guidelines-a systematic analysis]. / "Deprescribing" in DGPPN-S3-Leitlinien ­ eine systematische Analyse.

BACKGROUND: Deprescribing of medication or psychotherapy represents a critical phase in treatment. The aim of the work is to systematically analyze recommendations for deprescribing medication and discontinuation of psychotherapy in the evidence- and consensus-based S3 guidelines of the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) to identify potential research gaps. METHODS: A systematic analysis of the DGPPN S3 guidelines to investigate and compare information and recommendations on deprescribing. RESULTS: Regarding deprescribing of medication, our analysis showed that eight of the 20 included S3 guidelines contain information both in the form of recommendations and background information. Regarding psychotherapy, only two guidelines provided information on deprescribing. CONCLUSION: Our results highlight the need to expand guidelines to include evidence-based recommendations for deprescribing medication or discontinuation of psychotherapy. Future research should focus on the development of specific, generic, and evidence-based guidelines that support both medical staff and patients during these critical phases of therapy.

[Self-help offers for people with severe mental illness: who uses which format?] / Selbsthilfeangebote für Menschen mit schwerer psychischer Erkrankung ­ wer nutzt welches Format?

BACKGROUND: Self-help can play an important supplementary role in the treatment of people with severe mental illness; however, little is known about the utilization of the various approaches. OBJECTIVE: This study describes the use of various self-help options by patients with severe mental illness and examines potential predictors. MATERIAL AND METHODS: As part of the observational cross-sectional study on patients with severe mental illness (IMPPETUS, N = 397), trained staff collected sociodemographic, illness-associated and treatment-associated data between March 2019 and September 2019. Binary logistic regression was used to analyze a possible association with the use of self-help. RESULTS: The participants most frequently reported using self-help literature (n = 170; 45.5%) followed by self-help groups (n = 130; 33.2%), electronic mental health applications (n = 56; 15.5%) and self-management approaches (n = 54; 14.8%). Trialogue seminars (n = 36; 9.9%) were the least used by the participants. The utilization of the various approaches is influenced by sociodemographic and disease-related characteristics (age, education, marital status, migration background, age at onset of initial mental health problems, psychosocial functioning level) but not by factors associated with treatment. CONCLUSION: The potential of self-help is not being fully utilized in the sample investigated. The reported use of self-help approaches by the participants ranged between 10% and 46%. The various formats address specific target groups. More targeted information must be provided about the various options and the use of self-help in routine treatment must be actively fostered in order to increase the utilization of self-help.

[Acute Treatment Of Schizophrenia]. / Akutbehandlung der Schizophrenie.

Schizophrenia is one of the most common, most severe and most costly mental illnesses in adults. In the acute phase, sufferers usually experience massive anxiety and a high level of distress due to their altered perception. If the symptoms are severe, psychiatric emergencies can arise. The earliest possible antipsychotic treatment, which is felt to be appropriate by those affected, is essential for acute treatment.

[Inpatient Treatment of Mentally Ill Prisoners in General Psychiatric Departments and Hospitals]. / Status der stationären Behandlung psychisch erkrankter Strafgefangener in allgemeinpsychiatrischen Abteilungen und Kliniken.

BACKGROUND: Inpatient psychiatric treatment of prisoners is organized differently in Germany, depending on the structural conditions of the federal state and prison. There are very few findings on the different possibilities of treatment and the view of the hospitals on this issue. OBJECTIVES: Our aim was to gain an up-to-date picture of inpatient treatment of prisoners in general psychiatric departments and hospitals and the challenges these institutions face. METHODS: We conducted an anonymous online survey of the frequency, extent, and challenges of inpatient treatment of prisoners. Approximately 460 chief physicians of German general psychiatric departments and hospitals were invited to participate in this survey. In addition to descriptive statistics, we calculated group differences by type of hospital and by subjective responsibility for inpatient care of prisoners. RESULTS: A total of 74 chief physicians surveyed participated; 51.4% of the surveyed hospitals provided psychiatric inpatient treatment to prisoners in 2020. Group differences between the different types of hospitals were found only for the presence of anticipated anxiety among regular inpatients. Various differences were found between responsible and non-responsible hospitals, especially with regard to organizational aspects. DISCUSSION: For the treatment of mentally ill prisoners, various organizational challenges as well as fears of hospital staff and fellow patients were mentioned by the participants. The type of hospital appears to play a subordinate role here, whereas the responsibility of the hospital for the inpatient treatment of mentally ill prisoners might be more decisive for anticipated concerns and barriers.

[Providing Cognitive Remediation Therapy to People with Schizophrenia: Results of a Survey in Psychiatric Clinics in Germany]. / Die Versorgung von an Schizophrenie erkrankten Menschen mit Kognitiver Remediationstherapie ­ Ergebnisse einer Befragung in psychiatrischen Kliniken in Deutschland.

Schizophrenia is accompanied by significant cognitive impairments, which often persist to a relevant extent after remission of clinical symptoms and has a negative impact on psychosocial functioning. These impairments are often experienced as very stressful by those affected. Under the umbrella term of Cognitive Remediation Therapy (CRT), evidence-based therapy options are available that improve both the respective cognitive target functions and the psychosocial functioning. According to expert recommendations, at least 20 sessions should be carried out, accompanied by qualified therapeutic staff. The current edition of the S3 treatment guideline schizophrenia of the German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology recommends CRT with the highest level of recommendation. It is unclear to what extent CRT has become part of routine inpatient care. Between July 2021 and May 2022, 395 psychiatric university hospitals and non-university psychiatric specialist hospitals in Germany were invited to fill in a 14-item questionnaire. A total of 103 institutions took part in the survey; 56.3% of these hospitals used at least one evidence-based CRT programme. Among the CRT programmes used, Cogpack, Rehacom and the Integriertes Psychologisches Therapieprogramm (IPT) were named most frequently. In 87.5% of the participating facilities, fewer than half of the people with schizophrenia received CRT. With regard to the clinics which used evidence-based CRT, 64.3% carried out fewer than 11 therapy sessions, 28.6% between 11 and 20 sessions and 7.2% more than 20 sessions. It is thus clear that CRT is not yet offered in all of the participating psychiatric hospitals in Germany, not yet for all people with schizophrenia, and not yet with sufficient intensity, with clinics indicating the need for more technical and personnel resources and more extensive development of competencies for CRT application.The low response rate of 26.1% and possible selection effects for participation in the study are addressed and are to be seen as limitations.

Higher Subjective Burden in Psychiatric Compared to Somatic Healthcare Workers in Germany During the first wave of the COVID-19 Pandemic.

The COVID-19 pandemic has posed unprecedented challenges for health care workers (HCWs) worldwide. While the adverse effects of the pandemic on the well-being of HCWs in general have now been established, little is known about the impact on HCWs of psychiatric hospitals (PHCWs). PHCWs are of special interest, given that they faced both an increase in infection rates among psychiatric patients as well as in mental strain of the general public due to consequences of the pandemic. The aim of the present study was to investigate how the pandemic affected PHCWs as well as possible differences between PHCWs and other health care workers (OHCWs) in Germany during the first wave of the pandemic. We conducted a country-wide anonymous online survey early during the first pandemic wave between April 15th and May 1st, 2020, to assess different aspects of subjective burden and perceived stress using 5-point Likert-scale questions. We analysed data of 1530 PHCWs and 2114 OHCWs and showed that PHCWs reported higher subjective burden and stress compared to OHCWs (p<0.001). Overall, nurses from both groups of HCWs showed higher ratings in subjective burden and stress than physicians. These higher ratings for subjective burden were even more pronounced for nurses working in psychiatric hospitals. Future research is needed to investigate the causes for PHCWs' increased stress and subjective burden, especially when taking into account the long-term effects of the pandemic, which may lead to further challenges and an ever-increasing workload, especially for PHCWs.

Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany.

Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study's aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as "probable psychiatric AE (pAE)," if well-characterized neuronal IgG autoantibodies were detected or "possible pAE" (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed.

Repositioning synthetic glucocorticoids in psychiatric disease associated with neural autoantibodies: a narrative review.

Synthetic glucocorticoids (sGCs) are a well-investigated and standard drug therapy for disorders associated with CNS inflammation. Less is known about treating psychiatric disorders associated with neural autoantibodies. Our aim is to elucidate the repositioning of sGCs in psychiatric diseases that co-exist with neural autoantibodies. We used PubMed to identify articles for this narrative review. To our knowledge, no randomized, placebo-controlled trials have yet been conducted on applying sGC to treat neural autoantibody-associated psychiatric disorders. We describe initial results of cohort studies and single cases or case series often associated with autoantibodies against membrane-surface antigens demonstrating a largely beneficial response to sGCs either as monotherapy or polytherapy together with other immunosuppressive agents. However, sGCs may be less efficient in patients with psychiatric diseases associated with autoantibodies directed against intracellular antigens. These results reveal potential benefits of the novel usage of sGCs for the indication of neural autoantibody-associated psychiatric disease. Further large-scale randomized, placebo-controlled trials are needed to discover whether sGCs are safe, well tolerated, and beneficial in subgroups of neural autoantibody-associated psychiatric diseases.

Effects of add-on Celecoxib treatment on patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame): study design and methodology of a multicentre randomized, placebo-controlled trial.

Neuroinflammation has been proposed to impact symptomatology in patients with schizophrenia spectrum disorders. While previous studies have shown equivocal effects of treatments with add-on anti-inflammatory drugs such as Aspirin, N-acetylcysteine and Celecoxib, none have used a subset of prospectively recruited patients exhibiting an inflammatory profile. The aim of the study is to evaluate the efficacy and safety as well as the cost-effectiveness of a treatment with 400 mg Celecoxib added to an ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. The "Add-on Celecoxib treatment in patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame)" is a multicentre randomized, placebo-controlled phase III investigator-initiated clinical trial with the following two arms: patients exhibiting an inflammatory profile receiving either add-on Celecoxib 400 mg/day or add-on placebo. A total of 199 patients will be assessed for eligibility by measuring blood levels of three pro-inflammatory cytokines, and 109 patients with an inflammatory profile, i.e. inflamed, will be randomized, treated for 8 weeks and followed-up for additional four months. The primary endpoint will be changes in symptom severity as assessed by total Positive and Negative Syndrome Scale (PANSS) score changes from baseline to week 8. Secondary endpoints include various other measures of psychopathology and safety. Additional health economic analyses will be performed. TargetFlame is the first study aimed at evaluating the efficacy, safety and cost-effectiveness of the antiphlogistic agent Celecoxib in a subset of patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. With TargetFlame, we intended to investigate a novel precision medicine approach towards anti-inflammatory antipsychotic treatment augmentation using drug repurposing. Clinical trial registration: http://www.drks.de/DRKS00029044 and https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00029044.