Medication-induced dystonia (MID) is a movement disorder (MD), characterized by involuntary sustained or intermittent muscle contractions, causing abnormal, often repetitive, movements, postures, or both. Although MID is commonly associated with the use of antipsychotics, it also occurs with many other medications widely used in clinical practice.

A systematic literature search (from inception to November 2023), using the PubMed and Embase databases, was conducted without language restriction for articles reporting on MID in people without pre-existing MDs, and this for all potentially relevant non-antipsychotic medications. A narrative synthesis of the available evidence was undertaken.

MID is common (1 to 10%) with certain antiemetics. Selective serotonin reuptake inhibitors and the antiepileptics valproate, carbamazepine, and lamotrigine are rarely (0.01 to 0.1%) or very rarely (<0.01%) associated with MID. All other medications are very rarely (<0.01%) associated with MID or have a risk that cannot be precisely estimated. The actual rate of dystonic reactions with most non-antipsychotic agents remains unknown, owing to misdiagnosis and underreporting in the scientific literature. In general, MID seems to occur more often in children and adolescents, even with a single low dose, and with polymedication. In most cases, MID is acute in onset (occurring within hours to days) and involves the head and neck.

Although MID is most common with dopamine receptor-blocking antiemetics, many other medications may also produce dystonic reactions, particularly in children and adolescents. Although such incidents remain rare, there are indications that MID is underreported for many classes of medications.

Living with major depressive disorder (MDD) reduces life expectancy, with respiratory disease being a significant threat. However, evidence on respiratory disease in this population has not yet been meta-analyzed.

This meta-analysis examines respiratory disease prevalence and odds ratio (OR) in patients with MDD and treatment resistant depression (TRD). A systematic literature search was conducted, with a snowball search of reference and citation lists. Inclusion criteria covered studies in MDD and TRD patients with confirmed diagnoses of respiratory diseases (asthma, chronic obstructive pulmonary disease [COPD], pneumonia, lung cancer, and tuberculosis), comparing with a control group when possible.

From 4,138 retrieved articles, 15 (including 476,927 individuals with MDD, 50,680 with TRD, and 1,108,979 control group) met the inclusion criteria. In MDD patients, COPD prevalence was 9.0% (95% CI: 3.8–19.6%), asthma 8.6% (95% CI: 5.7–12.8%), and pneumonia 2.5% (95% CI: 2.2–2.9%). In TRD patients, COPD prevalence was 9.9% (95% CI: 4.2–21.9%) and asthma 10.9% (95% CI: 10.7–11.2%), but meta-analysis limited to those diseases showed no significant relative risk differences. Compared to the general population, individuals with MDD had significantly higher rates of COPD (OR 1.79, 95% CI: 1.49–2.16), even higher in younger populations (1.85 [95% CI: 1.74–1.97]) and more prevalent in women.

This first meta-analysis on this topic shows that MDD is associated with an increased risk of respiratory illness compared to the general population. The prevalence of asthma doubles the mean described in the general population worldwide, and in COPD, women and younger people are at particular risk. Prevention policies are urgently needed.

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.

Recent stressful life events (SLEs) are an established risk factor for a range of psychiatric disorders. Animal studies have shown evidence of gray matter (GM) reductions associated with stress, and previous work has found similar associations in humans. However longitudinal studies investigating the association between stress and changes in brain structure are limited.

The current study uses longitudinal data from the UK Biobank and comprises 4,543 participants with structural neuroimaging and recent SLE data (mean age = 61.5 years). We analyzed the association between recent SLEs and changes in brain structure, determined using the longitudinal FreeSurfer pipeline, focusing on total GM volume and five a priori brain regions: the hippocampus, amygdala, anterior cingulate cortex, orbitofrontal cortex, and insula. We also examined if depression and childhood adversity moderated the relationship between SLEs and brain structure.

Individuals who had experienced recent SLEs exhibited a slower rate of hippocampal decrease over time compared to individuals who did not report any SLEs. Individuals with depression exhibited smaller GM volumes when exposed to recent SLEs. There was no effect of childhood adversity on the relationship between SLEs and brain structure.

Our findings suggest recent SLEs are not directly associated with an accelerated decline in brain volumes in a population sample of older adults, but instead may alter brain structure via affective disorder psychopathology. Further work is needed to investigate the effects of stress in younger populations who may be more vulnerable to stress-induced changes, and may yet pinpoint brain regions linked to stress-related disorders.

Many psychiatric and somatic comorbidities increase the risk of suicidal behavior, but the effect of co-existing comorbidities is sparsely elucidated. We described co-existence of psychiatric and somatic comorbidities and the influence of the combined comorbidity burden on the risk of suicidal behavior.

We defined two case populations above 10 years in the Danish health registries: those who 1) died by suicide (2010–2020) and 2) had an incident suicide attempt (2010–2021). Co-existing somatic and psychiatric comorbidities and relative odds of suicidal behavior at increasing comorbidity burden were assessed.

Among 5.9 million Danish citizens (2021), 6,257 individuals died by suicide whereas 30,570 had an incident suicide attempt. More than half had ≥2 co-existing psychiatric and/or somatic comorbidities. Of those who died by suicide, 18% had co-existing mood disorders and stress disorders, while 5% had both mood disorders and cancer. An 88-fold increase of odds for attempting suicide and a 35-fold increase of odds for suicide were observed among those with the highest combined burden of somatic and psychiatric comorbidities relative to those without. The presence of somatic comorbidities seemed to protect against suicide in older individuals.

Psychiatric and somatic comorbidities commonly co-exist in individuals with suicidal behavior. Higher combined burden of psychiatric and somatic comorbidities increased the odds of suicidal behavior, though the presence of somatic diseases had a potential protective effect on the risk of suicide in older individuals. This warrants collaboration and enhanced awareness of suicidal behavior risks across somatic and psychiatric departments.

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.

Recent advances in natural language processing (NLP), particularly in language processing methods, have opened new avenues in semantic data analysis. A promising application of NLP is data harmonization in questionnaire-based cohort studies, where it can be used as an additional method, specifically when only different instruments are available for one construct as well as for the evaluation of potentially new construct-constellations. The present article therefore explores embedding models’ potential to detect opportunities for semantic harmonization.

Using models like SBERT and OpenAI’s ADA, we developed a prototype application (“Semantic Search Helper”) to facilitate the harmonization process of detecting semantically similar items within extensive health-related datasets. The approach’s feasibility and applicability were evaluated through a use case analysis involving data from four large cohort studies with heterogeneous data obtained with a different set of instruments for common constructs.

With the prototype, we effectively identified potential harmonization pairs, which significantly reduced manual evaluation efforts. Expert ratings of semantic similarity candidates showed high agreement with model-generated pairs, confirming the validity of our approach.

This study demonstrates the potential of embeddings in matching semantic similarity as a promising add-on tool to assist harmonization processes of multiplex data sets and instruments but with similar content, within and across studies.

Treatment-resistant depression (TRD) affects 10–30% of patients with major depressive disorder, leading to increased comorbidities, higher mortality, and significant economic and social burdens. This study aimed to compare the efficacy and safety of bupropion and aripiprazole as augmentation therapies for TRD.

This population-based, retrospective cohort study included adults aged ≥18 years with a diagnosis of depressive disorder who met the criteria for TRD. Data were collected from a nationwide claims database in South Korea. Patients prescribed bupropion were matched 1:1 with those prescribed aripiprazole. Subgroup analyses were performed according to age. An as-treated analysis was performed as the primary analysis, and an intention-to-treat analysis was performed to identify different risk windows. The primary outcome was depression-related hospitalization, and the secondary outcomes were first-time diagnoses of movement disorder and seizure.

A total of 5,619 patients (bupropion: n = 1,568; aripiprazole: n = 4,051) were included in this study. Bupropion was associated with lower risks of hospitalization (hazard ratio [HR]: 0.51; 95% confidence interval [CI] 0.29–0.86) and movement disorders (HR: 0.56; 95% CI 0.36–0.85) than aripiprazole. No significant difference in seizure risk (HR: 0.65; 95% CI 0.30–1.31) was observed between the two treatments. The subgroup analysis of participants aged ≥60 years revealed no significant differences in the three outcomes between the two medications.

Bupropion augmentation is associated with a significantly lower risk of depression-related re-hospitalization and movement disorders in patients with TRD. Therefore, bupropion augmentation can be a comprehensive treatment strategy for TRD.

Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). This study evaluated its antidepressant and cognitive effects as a safe, effective, home-based therapy for MDD.

This double-blind, sham-controlled, randomized trial divided participants into low-intensity (1 mA, n = 47), high-intensity (2 mA, n = 49), and sham (n = 45) groups, receiving 42 daily tDCS sessions, including weekends and holidays, targeting the dorsolateral prefrontal cortex for 30 minutes. Assessments were conducted at baseline and weeks 2, 4, and 6. The primary outcome was cognitive improvement assessed by changes in total accuracy on the 2-back test from baseline to week 6. Secondary outcomes included changes in depressive symptoms (HAM-D), anxiety (HAM-A), and quality of life (QLES). Adverse events were monitored. This trial was registered with ClinicalTrials.gov (NCT04709952).

In the tDCS study, of 141 participants (102 [72.3%] women; mean age 35.7 years, standard deviation 12.7), 95 completed the trial. Mean changes in the total accuracy scores from baseline to week 6 were compared across the three groups using an F-test. Linear mixed-effects models examined the interaction of group and time. Results showed no significant differences among groups in cognitive or depressive outcomes at week 6. Active groups experienced more mild adverse events compared to sham but had similar rates of severe adverse events and dropout.

Home-based tDCS for MDD demonstrated no evidence of effectiveness but was safe and well-tolerated. Further research is needed to address the technical limitations, evaluate broader cognitive functions, and extend durations to evaluate its therapeutic potential.