Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used due to their profound efficacy in glycemic control and weight management. Real-world observations have revealed potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs. This study aimed to comprehensively investigate and characterize these neuropsychiatric AEs with GLP-1RAs.

We analyzed GLP-1RA adverse reaction reports using the FDA Adverse Event Reporting System database. Disproportionality analysis using reporting odds ratio (ROR) identified eight categories of neuropsychiatric AEs associated with GLP-1RAs. We conducted descriptive and time-to-onset (TTO) analyses and explored neuropsychiatric AE signals among individual GLP-1RAs for weight loss and diabetes mellitus (DM) indications.

We identified 25,110 cases of GLP-1RA-related neuropsychiatric AEs. GLP-1RAs showed an association with headache (ROR 1.74, 95% confidence interval [CI] 1.65–1.84), migraine (ROR 1.28, 95%CI 1.06–1.55), and olfactory and sensory nerve abnormalities (ROR 2.44, 95%CI 1.83–3.25; ROR 1.69, 95%CI 1.54–1.85). Semaglutide showed a moderate suicide-related AEs signal in the weight loss population (ROR 2.55, 95%CI 1.97–3.31). The median TTO was 16 days (interquartile range: 3–66 days).

In this study, we identified eight potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs and, for the first time, detected positive signals for migraine, olfactory abnormalities, and sensory abnormalities. We also observed positive suicide-related signals of semaglutide, in weight loss population. This study provides a reliable basis for further investigation of GLP-1RA-related neuropsychiatric AEs. However, as an exploratory study, our findings require confirmation through large-scale prospective studies.

Despite uncertain benefits, antidepressants are used in the management of personality disorders (PDs). We investigated the association between antidepressants and two adverse outcomes - suicidal behaviour and violent crimes - in individuals with PDs.

We used nationwide Danish healthcare registries to identify all individuals with a diagnosed PD aged 18–64 years from 2007 to 2016. Antidepressant use was identified using dispensed prescriptions. Individuals were followed up for healthcare presentations of suicidal behaviour and separately for police-recorded charges of violent crimes. We applied a within-individual design comparing rates of suicidal behaviour and violent crimes during time periods of antidepressant treatment with periods without treatment. Subgroup analyses were performed according to PD clusters, individual antidepressants, specific PDs, psychiatric comorbidities, and history of suicidal behaviour and violent crime.

The cohort included 167,319 individuals with a diagnosed PD, 19,519 (12%) of whom were prescribed antidepressants and presented at least one outcome event during follow-up, making them eligible for within-individual analyses. Overall, we found an association with lower rates of suicidal behavior during periods of antidepressant treatment, compared with periods when individuals were not on antidepressants (incidence rate ratio 0.86, 95% CI 0.84–0.89). However, this association was modified by specific PDs, individual antidepressants, comorbidities, and past history. For violent crimes, we did not observe consistent associations in any direction.

Antidepressants were associated with lower rates of suicidal behaviour, but less clearly in violent crimes. Types of PDs, individual antidepressants, and comorbidities modified these associations.

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.

Current knowledge on psychiatric illness following periods of social distancing during the COVID-19 pandemic is mostly limited to smaller studies in selected populations. This nationwide study of all 4.6 million Danish adults examined if periods of social distancing were associated with changes in surrogate measures of mental health.

All Danish adults (≥18 years) were included and rates of collection of antidepressant prescriptions, psychiatric hospital admissions, and suicide or suicide attempts for the periods March 12, 2020–May 20, 2020 (lockdown period 1), and December 21, 2020–March 1, 2021 (lockdown period 2), were compared to corresponding periods 1 year prior. Individuals were censored due to death or SARS-CoV-2 infection.

Antidepressant consumption increased for both period 1 and period 2, with an incidence rate ratio (IRR) of 1.02 (95% CI: 1.01–1.02, p < 0.001) and IRR 1.08 (95% CI: 1.08–1.09, p < 0.001) respectively, compared to the control periods. Psychiatric hospitalization rates decreased significantly, with an IRR of 0.65 (95% CI: 0.63–0.66, p < 0.001) for period 1, and IRR 0.86 (95% CI: 0.84–0.88, p < 0.001) for period 2. The risk of suicide did not increase in period 1, IRR 0.96 (95% CI: 0.82–1.13, p = 0.64), but seemed increased during period 2, IRR 1.19 (95% CI: 1.02–1.38, p = 0.03).

Periods of social distancing during the COVID-19 pandemic were associated with an increase of antidepressant consumption, but decreased rates of psychiatric hospitalization. Suicide risk seemed increased during the second lockdown period.

Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.

We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10–28 years; N = 4,835) and UK Biobank (39–86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8).

Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.

These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

Childhood maltreatment (CM) significantly increases the risk of developing post-traumatic stress disorder (PTSD) for which the prevalence in Europe is higher than initially assumed. While the high economic burden of PTSD is well-documented, little is known about the health care cost differences between individuals with PTSD-CM and those without PTSD in Germany. This study aimed to determine the excess health care and absenteeism costs associated with PTSD-CM in Germany.

Baseline data from a multi-center randomized controlled trial on individuals with PTSD-CM (n = 361) were combined with data from individuals without PTSD (n = 4760). Entropy balancing was used to balance the data sets with regard to sociodemographic characteristics. Six-month excess health care costs from a societal perspective were calculated for 2022, using two-part models with logit specification for the first part and a generalized linear model for the second part.

The total six-month excess costs associated with PTSD-CM were €8864 (95% CI: €6855 to €10,873) per person. Of this, the excess health care costs accounted for €4647 (95% CI €3296 to €5997) and the excess costs of absenteeism for €4217 (95% CI: €3121 to €5314). Individuals with mild to moderate PTSD symptoms incurred total excess costs of €6038 (95% CI: €3879 to €8197), while those with severe to extreme symptoms faced €11,433 (95% CI: €8220 to €14,646).

Excess health care and absenteeism costs associated with PTSD-CM were substantial, with absenteeism accounting for roughly half of the total excess costs.

Beyond psychosis prediction, clinical high-risk (CHR-P) symptoms show clinical relevance by their association with functional impairments and psychopathology, including personality pathology. Impaired personality functioning is prioritized in recent dimensional personality disorder models (DSM-5, ICD-11), yet underexplored in CHR-P, as are associations with cognitive biases, which early studies indicate as possibly linking CHR-P-symptoms and personality pathology.

A community sample (N = 444, 17–60 years, 61.8% female) was assessed via clinical telephone interview and online questionnaires. Using zero-inflated Poisson models, we explored associations of personality functioning, cognitive biases, current psychopathology, and psychosocial functioning with likelihood and severity of overall CHR-P, as well as perceptive (per-) and non-perceptive (nonper-)CHR-P-symptoms distinctly.

Higher nonper-CHR-P-symptom likelihood was associated with more impaired personality functioning and psychosocial functioning, while more severe cognitive biases were associated with higher CHR-P- and per-CHR-P-symptom likelihood, alongside higher CHR-P- and nonper-CHR-P-symptom severity. Further, more axis-I diagnoses were linked to higher CHR-P-, per-CHR-P-, and nonper-CHR-P-symptom likelihood, and younger age to higher CHR-P- and per-CHR-P-symptom severity, with CHR-P-symptom severity appearing higher in females. In an exploratory analysis, personality functioning elements identity and self-direction, and cognitive biases dichotomous thinking, emotional reasoning, and catastrophizing, respectively, showed multifaceted associations with nonper-CHR-P-symptom likelihood and overall CHR-P-symptom expression.

Our study supports the association of CHR-P-symptoms with multiple mental health factors. Findings suggest intricate associations between personality functioning impairments and cognitive biases with CHR-P-symptom expression in non-help-seeking populations, possibly contributing to different per-CHR-P- and nonper-CHR-P-symptom expression patterns. Therefore, they should be targeted in future longitudinal studies, aiming at better understanding CHR-P-manifestations to inform preventive intervention.

A variety of treatment options for people with alcohol use disorder (AUD) exist. Surveys estimate that 1 in 10 people with AUD utilise treatment, but real-world treatment pathways remain covert. This data-linkage study seeks to characterise treatment utilisation patterns to identify gaps in treatment access and delivery in Germany.

Linking individual-level data from three sources (statutory health insurance, pension funds, outpatient addiction care services) identified seven alcohol-related treatment types delivered in outpatient (brief psychiatric consultation; formal psychotherapy; pharmacotherapy; low-threshold counselling), inpatient (standard, somatic inpatient treatment; intensive inpatient treatment with somatic and psychosocial care), or either of the two settings (long-term rehabilitation treatment) during 2016–2021. For patients with a new AUD diagnosis (ICD-10: F10.1–9), treatment utilisation over 24 months was recorded and patterns were identified using latent class analyses.

Of n = 9,491 patients with a new AUD diagnosis, 30% utilised at least one alcohol-related treatment type. Treatment utilisation was associated with younger age, female sex, unemployment, German nationality, and lower physical comorbidity. Among treatment entrants, nearly half received only brief psychiatric consultation. A similar share of patients utilised standard or intensive inpatient treatment; the latter occasionally followed by rehabilitation treatment. Formal psychotherapy, low-threshold counselling, and pharmacotherapy were rarely utilised and were mostly used in conjunction with other treatments.

The real-world utilisation of alcohol-related treatments contrasts with existing guidelines, as most patients with diagnosed AUD do not receive adequate care. Structural and social barriers should be minimised to ensure healthcare provision for those affected.