The development of guidelines is time-consuming and cost-intensive. The heterogeneity of clinical practice, evidence, and patients’ needs is an issue across Europe. An European core guidance for a specific psychiatric disorder may help to overcome this issue. Here, we present a progress report on the European Psychiatric Association (EPA) proof-of-concept approach to develop a European consensus guidance on the pharmacological treatment of schizophrenia.

All national psychiatric associations in Europe were contacted to provide their schizophrenia guidelines. Six guidelines were rated by three experts, experienced in the development of national and international guidelines, from three different countries (Italy, Hungary, and Germany), and the German schizophrenia guideline published in 2019 was found to have the highest quality. For this proof-of-concept approach, 45 recommendations on the pharmacological treatment of schizophrenia from the German guideline were evaluated in a two-step Delphi process to determine their acceptability throughout the European continent.

44 experts participated in the first round and 40 experts in the second round of the Delphi process. Agreement among the involved experts was reached for 75% of the presented recommendations from the German schizophrenia guidelines. 11 out of 45 recommendations (24.4%) did not reach this level of agreement.

This progress report highlights the possibility of developing a pan-European core guidance on the pharmacological treatment of schizophrenia by adapting national guidelines and reconciling their recommendations. However, several barriers in this adaptation process, such as non-agreement in recommendations with strong scientific evidence in the reconciling process, were identified and must be considered when developing the final guidance.

Dropout from healthcare interventions can negatively affect patients and healthcare providers through impaired trust in the healthcare system and ineffective use of resources. Research on this topic is still largely missing on refugees and asylum seekers. The current study aimed to characterize predictors for dropout in the Mental Health in Refugees and Asylum Seekers (MEHIRA) study, one of the largest multicentered controlled trials investigating the effectiveness and cost-effectiveness of a nationwide stepped and collaborative care model.

Predictors were multiply imputed and selected for descriptive modelling using backward elimination. The final variable set was entered into logistic regression.

The overall dropout rate was 41,7%. Dropout was higher in participants in group therapy (p = 0.001; OR = 10.7), with larger satisfaction with social relationships (p = 0.017; OR = 1.87), with difficulties in maintaining personal relationships (p = 0.005; OR = 4.27), and with higher depressive symptoms (p = 0.029; OR = 1.05). Participants living in refugee accommodation (p = 0.040; OR = 0.45), with a change in social status (p = 0.008; OR = 0.67) and with conduct (p = 0.020; OR = 0.24) and emotional problems (p = 0.013; OR = 0.31) were significantly less likely to drop out of treatment.

Overall, the outcomes of this study suggest that predictors assessing social relationships, social status, and living conditions should be considered as topics of psychological treatment to increase adherence and as predictors for future research studies (including treatment type).

Employment and relationship are crucial for social integration. However, individuals with major psychiatric disorders often face challenges in these domains.

We investigated employment and relationship status changes among patients across the affective and psychotic spectrum – in comparison with healthy controls, examining whether diagnostic groups or functional levels influence these transitions.

The sample from the longitudinal multicentric PsyCourse Study comprised 1260 patients with affective and psychotic spectrum disorders and 441 controls (mean age ± s.d., 39.91 ± 12.65 years; 48.9% female). Multistate models (Markov) were used to analyse transitions in employment and relationship status, focusing on transition intensities. Analyses contained multiple multistate models adjusted for age, gender, job or partner, diagnostic group and Global Assessment of Functioning (GAF) in different combinations to analyse the impact of the covariates on the hazard ratio of changing employment or relationship status.

The clinical group had a higher hazard ratio of losing partner (hazard ratio 1.46, P < 0.001) and job (hazard ratio 4.18, P < 0.001) than the control group (corrected for age/gender). Compared with controls, clinical groups had a higher hazard of losing partner (affective group, hazard ratio 2.69, P = 0.003; psychotic group, hazard ratio 3.06, P = 0.001) and job (affective group, hazard ratio 3.43, P < 0.001; psychotic group, hazard ratio 4.11, P < 0.001). Adjusting for GAF, the hazard ratio of losing partner and job decreased in both clinical groups compared with controls.

Patients face an increased hazard of job loss and relationship dissolution compared with healthy controls, and this is partially conditioned by the diagnosis and functional level. These findings underscore a high demand for destigmatisation and support for individuals in managing their functional limitations.

In patients with treatment resistant depression (TRD), the ESCAPE-TRD study showed esketamine nasal spray was superior to quetiapine extended release.

To determine the robustness of the ESCAPE-TRD results and confirm the superiority of esketamine nasal spray over quetiapine extended release.

ESCAPE-TRD was a randomised, open-label, rater-blinded, active-controlled phase IIIb trial. Patients had TRD (i.e. non-response to two or more antidepressive treatments within a major depressive episode). Patients were randomised 1:1 to flexibly dosed esketamine nasal spray or quetiapine extended release, while continuing an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. The primary end-point was achieving a Montgomery–Åsberg Depression Rating Scale score of ≤10 at Week 8, while the key secondary end-point was remaining relapse free through Week 32 after achieving remission at Week 8. Sensitivity analyses were performed on these end-points by varying the definition of remission based on timepoint, threshold and scale.

Of 676 patients, 336 were randomised to esketamine nasal spray and 340 to quetiapine extended release. All sensitivity analyses on the primary and key secondary end-point favoured esketamine nasal spray over quetiapine extended release, with relative risks ranging from 1.462 to 1.737 and from 1.417 to 1.838, respectively (all p < 0.05). Treatment with esketamine nasal spray shortened time to first and confirmed remission (hazard ratio: 1.711 [95% confidence interval 1.402, 2.087], p < 0.001; 1.658 [1.337, 2.055], p < 0.001).

Esketamine nasal spray consistently demonstrated significant superiority over quetiapine extended release using all pre-specified definitions for remission and relapse. Sensitivity analyses supported the conclusions of the primary ESCAPE-TRD analysis and demonstrated robustness of the results.

The hippocampal formation represents a key region in the pathophysiology of schizophrenia. Aerobic exercise poses a promising add-on treatment to potentially counteract structural impairments of the hippocampal formation and associated symptomatic burden. However, current evidence regarding exercise effects on the hippocampal formation in schizophrenia is largely heterogeneous. Therefore, we conducted a systematic review and meta-analysis to assess the impact of aerobic exercise on total hippocampal formation volume. Additionally, we used data from a recent multicenter randomized-controlled trial to examine the effects of aerobic exercise on hippocampal formation subfield volumes and their respective clinical implications.

The meta-analysis comprised six studies that investigated the influence of aerobic exercise on total hippocampal formation volume compared to a control condition with a total of 186 people with schizophrenia (100 male, 86 female), while original data from 29 patients (20 male, 9 female) was considered to explore effects of six months of aerobic exercise on hippocampal formation subfield volumes.

Our meta-analysis did not demonstrate a significant effect of aerobic exercise on total hippocampal formation volume in people with schizophrenia (g = 0.33 [−0.12 to 0.77]), p = 0.15), but our original data suggested significant volume increases in certain hippocampal subfields, namely the cornu ammonis and dentate gyrus.

Driven by the necessity of better understanding the pathophysiology of schizophrenia, the present work underlines the importance to focus on hippocampal formation subfields and to characterize subgroups of patients that show neuroplastic responses to aerobic exercise accompanied by corresponding clinical improvements.

Glutamatergic signalling deficits contribute to the neuropathology of cognitive symptoms in schizophrenia. Iclepertin (BI 425809), a glycine transporter-1 inhibitor, enhances N-methyl-D-aspartate receptor signalling in the brain by increasing synaptic levels of its co-agonist glycine. The Phase III CONNEX programme aims to assess the efficacy, safety and tolerability of iclepertin in improving cognition and functioning in schizophrenia.

CONNEX includes 3 randomised, double-blind, placebo-controlled parallel group trials in patients with schizophrenia from multiple centres across 41 countries in Asia, North and South America, Europe, and Asia Pacific Region (NCT04846868, NCT04846881, NCT04860830) receiving stable antipsychotic treatment. Each trial aims to recruit ~586 patients, 18–50 years old, treated with 1–2 antipsychotic medications (≥12 weeks on current drug; ≥35 days on current dose before treatment), who have functional impairment in day-to-day activities and interact ≥1 hour/week with a designated study partner. Patients with cognitive impairment due to developmental, neurological or other disorders, or receiving cognitive remediation therapy ≤12 weeks before screening will be excluded. Patients will be randomised 1:1 to once-daily oral iclepertin 10 mg (n = 293) or placebo (n = 293) for 26 weeks. Primary endpoint: change from baseline (CfB) in Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) overall composite T-score. Key secondary endpoints: CfB in Schizophrenia Cognition Rating Scale (SCoRS) total score and adjusted total time T-score in the Virtual Reality Functional Capacity Assessment Tool (VRFCAT).

Trial completion is expected in Q1 2025. By 31/01/2024, there have been 811, 699 and 655 patients screened, 533, 474 and 458 randomised, and 320, 299 and 281 who have completed the trial medication for CONNEX-1, -2 and -3, respectively. Most patients are male (CONNEX-1: 69.3%, CONNEX-2: 69.0%, CONNEX-3: 63.3%) with similar age (mean [standard deviation; SD]) (CONNEX-1: 34.0 [8.9], CONNEX-2: 35.9 [8.4], CONNEX-3: 34.0 [8.8] years). For CONNEX-1, -2 and -3, mean (SD) duration of illness is 10.6 (8.3), 12.2 (7.9) and 9.6 (7.6) years and duration of previous schizophrenia treatment is 3.9 (4.6), 4.5 (4.9) and 3.3 (4.4) years. Baseline mean (SD) MCCB overall composite T-score (1: 28.4 [13.7], 2: 27.3 [13.8], 3: 29.7 [13.7]), SCoRS total score (1: 40.5 [11.1], 2: 39.9 [9.7], 3: 38.0 [10.0]) and VRFCAT adjusted total time T-score (1: 29.6 [22.3], 2: 30.7 [20.8], 3: 33.6 [18.1]) were similar across trials.

If successful, CONNEX will provide evidence for iclepertin as the first efficacious medication addressing cognitive impairments in schizophrenia.

Studies funded by Boehringer Ingelheim.

Climate change is one of the greatest threats to health that societies face and can adversely affect mental health. Given the current lack of a European consensus paper on the interplay between climate change and mental health, we signal a need for a pan-European position paper about this topic, written by stakeholders working in mental health care.

On behalf of the European Psychiatric Association (EPA), we give recommendations to make mental health care, research, and education more sustainable based on a narrative review of the literature.

Examples of sustainable mental healthcare comprise preventive strategies, interdisciplinary collaborations, evidence-based patient care, addressing social determinants of mental health, maintaining health services during extreme weather events, optimising use of resources, and sustainable facility management. In mental health research, sustainable strategies include investigating the impact of climate change on mental health, promoting research on climate change interventions, strengthening the evidence base for mental health-care recommendations, evaluating the allocation of research funding, and establishing evidence-based definitions and clinical approaches for emerging issues such as ‘eco-distress’. Regarding mental health education, planetary health, which refers to human health and how it is intertwined with ecosystems, may be integrated into educational courses.

The EPA is committed to combat climate change as the latter poses a threat to the future of mental health care. The current EPA position paper on climate change and mental health may be of interest to a diverse readership of stakeholders, including clinicians, researchers, educators, patients, and policymakers.

Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians’ treatment choices for post-traumatic stress disorder (PTSD).

The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148).

About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct “profiles” of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines.

Clinicians’ decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders.

The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions.

About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15–20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome.

The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.

The European Psychiatric Association (EPA) is an organization that speaks on behalf of its individual members and members of National Psychiatric Associations (NPAs). The aim of this study to identify and investigate current contents of ethical codes and practices in the countries belonging to EPA.

The study is an expert survey sent out to 44 representatives of 30 NPAs covering the following topics: the existence of national bodies dealing with ethical issues in psychiatry, the availability of documents relevant to ethical issues, the types of ethical issues addressed at the national level, and the current and envisaged ethical debates.

Out of 44 experts invited to participate in the study, 31 NPAs from 30 countries responded (response rate 70.45%). In the majority of countries, the general mission statement serves as the main document covering ethical issues in psychiatry. Most frequently, internal documents were reported to address medical malpractice, workplace bullying, plagiarism, academic fraud, sexual abuse, and discrimination/racism. Furthermore, internal documents cover the ethical assessment of potentially controversial procedures, including psychosurgery, euthanasia, and pregnancy termination. The most important topics for debate at the level of NPAs/EPA were associated with violations of clinical practice standards and human rights.

NPAs are active in the field of professional ethics, defining ethical standards related to interactions among professionals and services provided by mental health care professionals. Future collaboration of NPAs, under the umbrella of the EPA, could allow to develop a database of local ethical documents that would be translated into English and accessible to all EPA members.