Anxiety disorders are a major public health burden with limited treatment options.

We investigated the long-term safety and efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with anxiety with or without life-threatening illness.

This study was an a priori-planned long-term follow-up of an investigator-initiated, two-centre trial that used a double-blind, placebo-controlled, two-period, random-order, crossover design with two sessions with either oral LSD (200 μg) or placebo per period. Participants (n = 39) were followed up 1 year after the end-of-study visit to assess symptoms of anxiety, depression and long-term effects of psychedelics using Spielberger's State-Trait Anxiety Inventory–Global (STAI-G), the Beck Depression Inventory (BDI), the Persisting Effects Questionnaire and measures of personality traits using the NEO-Five-Factor Inventory.

Participants reported a sustained reduction of STAI-G scores compared with baseline (least square means (95% CI) = −21.6 (−32.7, −10.4), d = 1.04, P < 0.001, for those who received LSD in the first period (94 weeks after the last LSD treatment) and −16.5 (−26.2, −6.8), d = 1.02, P < 0.05, for those who received LSD in the second period (68 weeks after the last LSD treatment)). Similar effects were observed for comorbid depression with change from baseline BDI scores of −8.1 (−13.2, −3.1), d = 0.71, P < 0.01, and −8.9 (−12.9, −4.9), d = 1.21, P < 0.01, for the LSD-first and placebo-first groups, respectively. Personality trait neuroticism decreased (P < 0.0001) and trait extraversion increased (P < 0.01) compared with study inclusion. Individuals attributed positive long-term effects to the psychedelic experience.

Patients reported sustained long-term effects of LSD-assisted therapy for anxiety.

Attempts to use artificial intelligence (AI) in psychiatric disorders show moderate success, highlighting the potential of incorporating information from clinical assessments to improve the models. This study focuses on using large language models (LLMs) to detect suicide risk from medical text in psychiatric care.

To extract information about suicidality status from the admission notes in electronic health records (EHRs) using privacy-sensitive, locally hosted LLMs, specifically evaluating the efficacy of Llama-2 models.

We compared the performance of several variants of the open source LLM Llama-2 in extracting suicidality status from 100 psychiatric reports against a ground truth defined by human experts, assessing accuracy, sensitivity, specificity and F1 score across different prompting strategies.

A German fine-tuned Llama-2 model showed the highest accuracy (87.5%), sensitivity (83.0%) and specificity (91.8%) in identifying suicidality, with significant improvements in sensitivity and specificity across various prompt designs.

The study demonstrates the capability of LLMs, particularly Llama-2, in accurately extracting information on suicidality from psychiatric records while preserving data privacy. This suggests their application in surveillance systems for psychiatric emergencies and improving the clinical management of suicidality by improving systematic quality control and research.

Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups.

To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire.

Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas.

A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased.

Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence.

Childhood trauma is a major risk factor for chronic depression. It has been suggested that adults with chronic depression who have experienced childhood trauma may require long-term treatment owing to a breakdown of basic trust and related difficulties in developing a productive therapeutic relationship.

As empirical studies have been preliminary and scarce, we studied the effects of psychoanalytic therapy (PAT) versus cognitive–behavioural therapy (CBT) for chronic depression in adults with a history of childhood trauma. In this subgroup, we expected a greater symptom reduction in PAT compared with CBT.

In a large trial of long-term psychotherapies for chronic depression (LAC-Study; Clinical Trial Register ISRCTN91956346), 210 adults received open-ended CBT or PAT in an out-patient setting and were examined yearly over 5 years on the Beck Depression Inventory – II (BDI-II). Based on a linear mixed model approach, we tested participant-reported childhood trauma based on the Childhood Trauma Questionnaire (CTQ) as a predictor and moderator of treatment outcome. CTQ subscales were examined exploratively.

Depressive symptoms decreased over time (b = −4.55, s.e. = 0.90, 95% CI −6.32 to −2.81, T = −5.08; P < 0.001). A significant three-way interaction between childhood trauma, time and therapy group (b = −0.05, s.e. = 0.02, 95% CI −0.09 to −0.01, T = −2.42; P = 0.016) indicated that participants with childhood trauma profited especially well from PATs.

Our results indicate differential benefits from PAT compared with CBT among adults with chronic depression and a history of childhood trauma. The results have important implications for differential indication and policy.

Clozapine is the most effective antipsychotic for treatment-resistant psychosis. However, clozapine is underutilised in part because of potential agranulocytosis. Accumulating evidence indicates that below-threshold haematological readings in isolation are not diagnostic of life-threatening clozapine-induced agranulocytosis (CIA).

To examine the prevalence and timing of CIA using different diagnostic criteria and to explore demographic differences of CIA in patients registered on the UK Central Non-Rechallenge Database (CNRD).

We analysed data of all patients registered on the UK Clozaril® Patient Monitoring Service Central Non-Rechallenge Database (at least one absolute neutrophil count (ANC) < 1.5 × 109/L and/or white blood cell count < 3.0 × 109/L) between May 2000 and February 2021. We calculated prevalence rates of agranulocytosis using threshold-based and pattern-based criteria, stratified by demographic factors (gender, age and ethnicity). Differences in epidemiology based on rechallenge status and clozapine indication were explored. The proportion of patients who recorded agranulocytosis from a normal ANC was explored.

Of the 3029 patients registered on the CNRD with 283 726 blood measurements, 593 (19.6%) were determined to have threshold-based agranulocytosis and 348 (11.4%) pattern-based agranulocytosis. In the total sample (75 533), the prevalence of threshold-based agranulocytosis and pattern-based agranulocytosis was 0.8% and 0.5%, respectively. The median time to threshold-based agranulocytosis was 32 weeks (IQR 184) and 15 (IQR 170) weeks for pattern-based agranulocytosis. Among age groups, the prevalence of pattern-based agranulocytosis and threshold-based agranulocytosis was highest in the >48 age group. Prevalence rates were greatest for White (18%) and male individuals (13%), and lowest for Black individuals (0.1%). The proportion of people who were determined to have pattern-based agranulocytosis without passing through neutropenia was 70%.

Threshold-based definition of agranulocytosis may over-diagnose CIA. Monitoring schemes should take into consideration neutrophil patterns to correctly identify clinically relevant CIA. In marked contrast to previous studies, CIA occurred least in Black individuals and most in White individuals.

Systemic changes in multiple diseases may influence the onset of dementia. However, the specific temporality between exposure diseases and dementia remains uncertain.

By characterising the full spectrum of temporal disease trajectories before dementia, this study aims to yield a global picture of precursor diseases to dementia and to provide detailed instructions for risk management and primary prevention of dementia.

Using the multicentre, community-based prospective UK Biobank, we constructed disease trajectories before dementia utilising the phenome-wide association analysis, paired directional test and association quantification. Stratified disease trajectories were constructed by dementia subtypes, gender, age of diagnosis and Apolipoprotein E (ApoE) status, respectively.

Our study population comprised 434 266 participants without baseline dementia and 4638 individuals with all-cause dementia. In total, 1253 diseases were extracted as potential components of the disease trajectory before dementia. We identified three clusters of disease trajectories preceding all-cause dementia, initiated by circulatory, metabolic and respiratory diseases occurring approximately 5–15 years before dementia. Cerebral infarction or chronic renal failure following chronic ischaemic heart disease was the specific trajectory before vascular dementia. Apolipoprotein E (ApoE) ε4 non-carriers exhibited more complex trajectories compared with carriers. Lipid metabolism disorders remained in the trajectories regardless of dementia subtypes, gender, age of diagnosis and ApoE status.

This study provides a comprehensive view of the longitudinal disease trajectories before dementia and highlights the potential targets of midlife cardiometabolic dysfunction for dementia screening and prevention.

Depression is a significant mental health concern affecting the overall well-being of adolescents and young adults. Recently, the prevalence of depression has increased among young people. Nonetheless, there is little research delving into the longitudinal epidemiology of adolescent depression over time.

To investigate the longitudinal epidemiology of depression among adolescents and young adults aged 10–24 years.

Our research focused on young people (aged 10–24 years) with depression, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We explored the age-standardised prevalence, incidence and disability-adjusted life-years (DALYs) of depression in different groups, including various regions, ages, genders and sociodemographic indices, from 1990 to 2019.

The prevalence, incidence and DALYs of depression in young people increased globally between 1990 and 2019. Regionally, higher-income regions like High-Income North America and Australasia recorded rising age-standardised prevalence and incidence rates, whereas low- or middle-income regions mostly saw reductions. Nationally, countries such as Greenland, the USA and Palestine reported the highest age-standardised prevalence and incidence rates in 2019, whereas Qatar witnessed the largest growth over time. The burden disproportionately affected females across age groups and world regions. The most prominent age effect on incidence and prevalence rates was in those aged 20–24 years. The depression burden showed an unfavourable trend in younger cohorts born after 1980, with females reporting a higher cohort risk than males.

Between 1990 and 2019, the general pattern of depression among adolescents varied according to age, gender, time period and generational cohort, across regions and nations.

Higher intensity of psychotherapy might improve treatment outcome in depression, especially in those with comorbid personality disorder.

To compare the effects of 25 individual sessions (weekly) of two forms of psychotherapy – short-term psychoanalytic supportive psychotherapy (SPSP) and schema therapy – with the same treatments given for 50 sessions (twice weekly) in people with depression and personality disorder. Trial registration: NTR5941.

We conducted a pragmatic, double-randomised clinical trial and, over 37 months, recruited 246 adult out-patients with comorbid depression/dysthymia and personality disorder. A 2 × 2 factorial design randomised participants to 25 or 50 sessions of SPSP or schema therapy. The primary outcome was change in depression severity over 1 year on the Beck Depression Inventory II (BDI-II). Secondary outcomes were remission both of depression and personality disorder.

Compared with 25 sessions, participants who received 50 sessions showed a significantly greater decrease in depressive symptoms over time (time × session dosage, P < 0.001), with a mean difference of 5.6 BDI points after 1 year (d = −0.53, 95% CI −0.18 to 0.882, P = 0.003). Remission from depression was also greater in the 50-session group (74% v. 58%, P = 0.025), as was remission of personality disorder (74% v. 56%, P = 0.010).

Greater intensity of psychotherapy leads to better outcomes of both depression and personality status in people with comorbid depression and personality disorder.

The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established.

To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system.

Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders.

Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76–0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69–0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses.

These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.

Despite strong evidence of efficacy of electroconvulsive therapy (ECT) in the treatment of depression, no sensitive and specific predictors of ECT response have been identified. Previous meta-analyses have suggested some pre-treatment associations with response at a population level.

Using 10 years (2009–2018) of routinely collected Scottish data of people with moderate to severe depression (n = 2074) receiving ECT we tested two hypotheses: (a) that there were significant group-level associations between post-ECT clinical outcomes and pre-ECT clinical variables and (b) that it was possible to develop a method for predicting illness remission for individual patients using machine learning.

Data were analysed on a group level using descriptive statistics and association analyses as well as using individual patient prediction with machine learning methodologies, including cross-validation.

ECT is highly effective for moderate to severe depression, with a response rate of 73% and remission rate of 51%. ECT response is associated with older age, psychotic symptoms, necessity for urgent intervention, severe distress, psychomotor retardation, previous good response, lack of medication resistance, and consent status. Remission has the same associations except for necessity for urgent intervention and, in addition, history of recurrent depression and low suicide risk. It is possible to predict remission with ECT with an accuracy of 61%.

Pre-ECT clinical variables are associated with both response and remission and can help predict individual response to ECT. This predictive tool could inform shared decision-making, prevent the unnecessary use of ECT when it is unlikely to be beneficial and ensure prompt use of ECT when it is likely to be effective.

Despite the recognised importance of mental disorders and social disconnectedness for mortality, few studies have examined their co-occurrence.

To examine the interaction between mental disorders and three distinct aspects of social disconnectedness on mortality, while taking into account sex, age and characteristics of the mental disorder.

This cohort study included participants from the Danish National Health Survey in 2013 and 2017 who were followed until 2021. Survey data on social disconnectedness (loneliness, social isolation and low social support) were linked with register data on hospital-diagnosed mental disorders and mortality. Poisson regression was applied to estimate independent and joint associations with mortality, interaction contrasts and attributable proportions.

A total of 162 497 individuals were followed for 886 614 person-years, and 9047 individuals (5.6%) died during follow-up. Among men, interaction between mental disorders and loneliness, social isolation and low social support, respectively, accounted for 47% (95% CI: 21–74%), 24% (95% CI: −15 to 63%) and 61% (95% CI: 35–86%) of the excess mortality after adjustment for demographics, country of birth, somatic morbidity, educational level, income and wealth. In contrast, among women, no excess mortality could be attributed to interaction. No clear trends were identified according to age or characteristics of the mental disorder.

Mortality among men, but not women, with a co-occurring mental disorder and social disconnectedness was substantially elevated compared with what was expected. Awareness of elevated mortality rates among socially disconnected men with mental disorders could be of importance to qualify and guide prevention efforts in psychiatric services.

Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation.

We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date.

We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days.

Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset.

A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.

The longitudinal course of late-life depression remains under-studied.

To describe transitions along the depression continuum in old age and to identify factors associated with specific transition patterns.

We analysed 15-year longitudinal data on 2745 dementia-free persons aged 60+ from the population-based Swedish National Study on Aging and Care in Kungsholmen. Depression (minor and major) was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; subsyndromal depression (SSD) was operationalised as the presence of ≥2 symptoms without depression. Multistate survival models were used to map depression transitions, including death, and to examine the association of psychosocial (social network, connection and support), lifestyle (smoking, alcohol consumption and physical activity) and clinical (somatic disease count) factors with transition patterns.

Over the follow-up, 19.1% had ≥1 transitions across depressive states, while 6.5% had ≥2. Each additional somatic disease was associated with a higher hazard of progression from no depression (No Dep) to SSD (hazard ratio 1.09; 1.07–1.10) and depression (Dep) (hazard ratio 1.06; 1.04–1.08), but also with a lower recovery (HRSSD−No Dep 0.95; 0.93–0.97 [where ‘HR’ refers to ‘hazard ratio’]; HRDep−No Dep 0.96; 0.93–0.99). Physical activity was associated with an increased hazard of recovery to no depression from SSD (hazard ratio 1.49; 1.28–1.73) and depression (hazard ratio 1.20; 1.00–1.44), while a richer social network was associated with both higher recovery from (HRSSD−No Dep 1.44; 1.26–1.66; HRDep−No Dep 1.51; 1.34–1.71) and lower progression hazards to a worse depressive state (HRNo Dep−SSD 0.81; 0.70–0.94; HRNo Dep−Dep 0.58; 0.46–0.73; HRSSD−Dep 0.66; 0.44–0.98).

Older people may present with heterogeneous depressive trajectories. Targeting the accumulation of somatic diseases and enhancing social interactions may be appropriate for both depression prevention and burden reduction, while promoting physical activity may primarily benefit recovery from depressive disorders.

A clinical tool to estimate the risk of treatment-resistant schizophrenia (TRS) in people with first-episode psychosis (FEP) would inform early detection of TRS and overcome the delay of up to 5 years in starting TRS medication.

To develop and evaluate a model that could predict the risk of TRS in routine clinical practice.

We used data from two UK-based FEP cohorts (GAP and AESOP-10) to develop and internally validate a prognostic model that supports identification of patients at high-risk of TRS soon after FEP diagnosis. Using sociodemographic and clinical predictors, a model for predicting risk of TRS was developed based on penalised logistic regression, with missing data handled using multiple imputation. Internal validation was undertaken via bootstrapping, obtaining optimism-adjusted estimates of the model's performance. Interviews and focus groups with clinicians were conducted to establish clinically relevant risk thresholds and understand the acceptability and perceived utility of the model.

We included seven factors in the prediction model that are predominantly assessed in clinical practice in patients with FEP. The model predicted treatment resistance among the 1081 patients with reasonable accuracy; the model's C-statistic was 0.727 (95% CI 0.723–0.732) prior to shrinkage and 0.687 after adjustment for optimism. Calibration was good (expected/observed ratio: 0.999; calibration-in-the-large: 0.000584) after adjustment for optimism.

We developed and internally validated a prediction model with reasonably good predictive metrics. Clinicians, patients and carers were involved in the development process. External validation of the tool is needed followed by co-design methodology to support implementation in early intervention services.

Concern that self-harm and mental health conditions are increasing in university students may reflect widening access to higher education, existing population trends and/or stressors associated with this setting.

To compare population-level data on self-harm, neurodevelopmental and mental health conditions between university students and non-students with similar characteristics before and during enrolment.

This cohort study linked electronic records from the Higher Education Statistics Agency for 2012–2018 to primary and secondary healthcare records. Students were undergraduates aged 18 to 24 years at university entry. Non-students were pseudo-randomly selected based on an equivalent age distribution. Logistic regressions were used to calculate odds ratios. Poisson regressions were used to calculate incidence rate ratios (IRR).

The study included 96 760 students and 151 795 non-students. Being male, self-harm and mental health conditions recorded before university entry, and higher deprivation levels, resulted in lower odds of becoming a student and higher odds of drop-out from university. IRRs for self-harm, depression, anxiety, autism spectrum disorder (ASD), drug use and schizophrenia were lower for students. IRRs for self-harm, depression, attention-deficit hyperactivity disorder, ASD, alcohol use and schizophrenia increased more in students than in non-students over time. Older students experienced greater risk of self-harm and mental health conditions, whereas younger students were more at risk of alcohol use than non-student counterparts.

Mental health conditions in students are common and diverse. While at university, students require person-centred stepped care, integrated with local third-sector and healthcare services to address specific conditions.

Anorexia nervosa is a psychiatric disorder characterised by undernutrition, significantly low body weight and large, although possibly transient, reductions in brain structure. Advanced brain ageing tracks accelerated age-related changes in brain morphology that have been linked to psychopathology and adverse clinical outcomes.

The aim of the current case–control study was to characterise cross-sectional and longitudinal patterns of advanced brain age in acute anorexia nervosa and during the recovery process.

Measures of grey- and white-matter-based brain age were obtained from T1-weighted magnetic resonance imaging scans of 129 acutely underweight female anorexia nervosa patients (of which 95 were assessed both at baseline and after approximately 3 months of nutritional therapy), 39 recovered patients and 167 healthy female controls, aged 12–23 years. The difference between chronological age and grey- or white-matter-based brain age was calculated to indicate brain-predicted age difference (BrainAGEGM and BrainAGEWM).

Acute anorexia nervosa patients at baseline, but not recovered patients, showed a higher BrainAGEGM of 1.79 years (95% CI [1.45, 2.13]) compared to healthy controls. However, the difference was largely reduced for BrainAGEWM. After partial weight restoration, BrainAGEGM decreased substantially (beta = −1.69; CI [−1.93, −1.46]). BrainAGEs were unrelated to symptom severity or depression, but larger weight gain predicted larger normalisation of BrainAGEGM in the longitudinal patient sample (beta = −0.65; CI [−0.75, −0.54]).

Our findings suggest that in patients with anorexia nervosa, undernutrition is an important predictor of advanced grey-matter-based brain age, which itself might be transient in nature and largely undetectable after weight recovery.

Individuals with schizophrenia face high mortality risks. The effects of lipid-modifying agents on this risk remain understudied.

This study was conducted to investigate the effects of lipid-modifying agents on mortality risk in people with schizophrenia.

This nationwide cohort study collected the data of people with schizophrenia from Taiwan's National Health Insurance Research Database for the period between 1 January 2001 and 31 December 2019. Multivariable Cox proportional hazards regression with a time-dependent model was used to estimate the hazard ratio for mortality associated with each lipid-modifying agent.

This study included 110 300 people with schizophrenia. Of them, 22 528 died (19 754 from natural causes and 1606 from suicide) during the study period, as confirmed using data from Taiwan's national mortality database. The use of lipid-modifying agents was associated with reduced risks of all-cause (adjusted hazard ratio [aHR]:0.37; P < 0.001) and natural (aHR:0.37; P < 0.001) mortality during a 5-year period. Among the lipid-modifying agents, statins and fibrates were associated with reduced risks of all-cause mortality (aHRs:0.37 and 0.39, respectively; P < 0.001 for both) and natural mortality (aHRs: 0.37 and 0.42, respectively; P < 0.001 for both). Notably, although our univariate analysis indicated an association between the use of lipid-modifying agents and a reduced risk of suicide mortality, the multivariate analysis revealed no significant association.

Lipid-modifying agents, particularly statins and fibrates, reduce the risk of mortality in people with schizophrenia. Appropriate use of lipid-modifying agents may bridge the mortality gap between these individuals and the general population.

Understanding inequalities in outcomes between demographic groups is a necessary step in addressing them in clinical care. Inequalities in treatment uptake between demographic groups may explain disparities in outcomes in people with first-episode psychosis (FEP).

To investigate disparities between broad demographic groups in symptomatic improvement in patients with FEP and their relationship to treatment uptake.

We used data from 6813 patients from the 2021–2022 National Clinical Audit of Psychosis data-set. Data were grouped by category type to obtain mean outcomes before adjustment to see whether disparities in outcomes remained after differences in treatment uptake had been accounted for. After matching, the average effect of each demographic variable in terms of outcome change was calculated. Moderator effects on specific treatments were investigated using interaction terms in a regression model.

Observational results showed that patients aged 18–24 years were less likely to improve in outcome, unless adjusted for intervention uptake. Patients classified as Black and Black British were less likely to improve in outcome (moderation effect 0.04, 95% CI 0–0.07) after adjusting for treatment take-up and demographic factors. Regression analysis showed the general positive effect of supported employment interventions in improving outcomes (coefficient −0.13, 95% CI −0.07 to −0.18, P < 0.001), and moderator analysis suggested targeting particular groups for interventions.

Inequalities in treatment uptake and psychotic symptom outcome of FEP by social and demographic factors require monitoring over time. Our analysis provides a framework for monitoring health inequalities across national clinical audits in the UK.