Epidemiology and Psychiatric Sciences

BackgroundNon-medical use of prescription psychotropic medications (NMUPM) among adolescents and young adults in low- and middle-income countries (LMICs) is an emerging public health concern. Such practices are associated with psychiatric comorbidities, increased risk behaviors, and long-term dependence. Limited access to mental health services, weak regulatory enforcement, and the widespread availability of prescription drugs contribute to NMUPM. Despite anecdotal reports, comprehensive epidemiological synthesis across LMICs is scarce. ObjectiveTo systematically review the prevalence, patterns, psychiatric correlates, and health-system drivers of NMUPM among young people (aged 10-35 years) in LMICs and provide a pooled estimate of prevalence through meta-analysis. MethodsWe conducted a systematic review following the PRISMA 2020 guidelines. PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycInfo, LILACS, AJOL, WHO GIM, Google Scholar, and regional LMIC repositories were searched for studies published between 2000 and 2026 reporting NMUPM among adolescents and young people. Inclusion criteria comprised cross-sectional surveys, community or school-based studies, and national or regional surveillance reports. Data were extracted on sample size, prevalence, commonly misused drugs, sources of medication, and motivations. A random-effects generalized linear mixed model (GLMM) with logit transformation was used to estimate pooled prevalence, and heterogeneity was assessed using I{superscript 2} statistics. Risk of bias was evaluated using the Joanna Briggs Institute (JBI) checklist. ResultsA total of 13 studies were included in the systematic review, with 10 studies (N = 6,728 participants) suitable for quantitative meta-analysis. The pooled prevalence of NMUPM among young people in LMICs was 18.4% (95% CI: 12.1-26.2%), with substantial heterogeneity (I{superscript 2} > 90%). Benzodiazepines and tramadol were the most commonly misused drugs. Primary drivers included prior experience with medications, ease of access through pharmacies or peers, and limited awareness of potential harms. NMUPM was associated with psychiatric symptoms, risky behaviors, and early progression to substance use disorders. ConclusionNon-medical use of psychotropic medications is prevalent among adolescents and young adults in LMICs, posing significant psychiatric and public health challenges. Interventions are urgently needed to strengthen regulatory enforcement, improve public awareness, enhance mental health service accessibility, and promote safe medication practices. Future research should focus on longitudinal studies to clarify causal pathways and test behavioral interventions to reduce NMUPM.

BackgroundSuicide prevention has become a global public health priority, and Brief Contact Interventions (BCI) following suicide attempts (SA) are an important tool for preventing suicides. The VigilanS project was designed to generalize compounded BCIs at the entire population level., It involves resource cards, telephone calls, and mailings, following a predefined algorithm. It has been implemented progressively in France, on a region-by-region basis, since 2015. ObjectiveTo evaluate the effectiveness of VigilanS in reducing suicide attempts among patients aged 18 years and older, and to explore potential differences in effectiveness by sex, age, and geographical location. MethodsThe study used data from the French national hospitalization database, PMSI-MCO. It included all patients over age 18 who were admitted to general hospitals for suicide attempts, between 2012 and 2022. Time-to-event ("survival") analysis of a second SA after a first one was performed; patients whose first SA occurred before VigilanS implementation were compared with their after-VigilanS counterparts. Six regions, with implementation occurring between 2015 and 2017, are analyzed here. ResultsThe differences in distribution of time-to-new-SA among patients before and after VigilanS implementation were statistically significant in all six regions under scope (log-rank test: P<0.0001). The Cox regression analysis revealed that VigilanS was significantly associated with a reduced risk of reattempting suicide in all regions. Age consistently showed a negative association with reattempting suicide. ConclusionVigilanS is likely effective in reducing suicide attempts among patients aged 18 years and older in France. This suggests that implementing BCIs following SAs in general hospitals at a population-wide level can contribute to reducing suicide rates and provides real-world evidence (RWE).

KEY POINTSO_ST_ABSQuestionC_ST_ABSDid changes in mental health symptoms from pre-COVID-19 to during the pandemic differ by sex or gender? FindingsIn this systematic review and meta-analysis study of findings from 27 unique cohorts, changes from before to during the COVID-19 pandemic in mental health symptoms, including general mental health, anxiety, depression, and stress, were not statistically significantly different by sex or gender. MeaningThere were not likely substantial sex and gender differences in mental health symptom changes during the COVID-19 pandemic. ImportanceConcerns remain about whether COVID-19 affected mental health differently across sex or gender groups. We previously reported that changes in general mental health and anxiety symptoms, but not depression or stress, worsened more for females or women than males or men, but that was based on 12 studies published up to August 2021. ObjectiveTo investigate the sex or gender differences in mental health symptoms before and during the COVID-19 pandemic with updated evidence. Data SourcesMEDLINE, PsycINFO, CINAHL, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, medRxiv, Open Science Framework Preprints searched to August 31, 2023. Study SelectionEligible studies included change data for general mental health, anxiety symptoms, depression symptoms, or stress from pre-to during COVID-19 by sex or gender. Two independent reviewers reviewed citations for eligibility. Data Extraction and SynthesisStandardized mean differences (SMDs) were extracted for changes of continuous outcomes and proportions for dichotomous outcomes. Two independent reviewers completed data extraction and risk of bias assessment with an adapted Joanna Briggs Institute Checklist for Prevalence Studies. Data were pooled by random-effects models. Main Outcomes and MeasuresDifference in change of SMDs and proportions between sex or gender groups pre-COVID-19 to COVID-19. ResultsWe included data from 27 unique cohorts (N = 102 to 18,127). Change differences by sex or gender were minimal and not statistically significant: general mental health (SMD changewomen-men = 0.01, 95% confidence interval [CI]:-0.07 to 0.10; proportion changewomen-men = -0.03, 95% CI: -0.08 to 0.03), anxiety (SMD changewomen-men = 0.09, 95% CI -0.04 to 0.22; proportion changewomen-men = -0.05, 95% CI: -0.20 to 0.11), depression (SMD changewomen-men = 0.10, 95% CI: -0.00 to 0.20; proportion changewomen-men = -0.13, 95% CI: -0.81 to 0.55), and stress (SMD changewomen-men = -0.08, 95% CI -0.16 to 0.01, proportion changewomen-men = 0.04, 95% CI -0.10 to 0.17). No studies reported eligible mental health outcomes for gender minorities. Conclusion and RelevanceWe found no significant sex or gender differences in mental health changes. Future research should report outcomes for gender minority groups, even if small numbers, to support evidence synthesis. RegistrationPROSPERO (CRD42020179703)

BackgroundForensic psychiatric services are expanding in many countries, and discharging patients from secure hospitals relies on accurate estimates of risk of adverse outcomes. Novel evidence-based tools for estimating one key risk, violent reoffending, have been developed in recent years. We aimed to externally validate one new tool, FoVOx, in forensic psychiatric patients sentenced to treatment, and to develop an updated model (FoVOx2), incorporating additional clinical predictors. MethodsUsing Swedish national registers, we conducted a temporal external validation of FoVOx by examining 767 patients discharged between 2014 and 2023. For the FoVOx2 cohort, 906 patients discharged between 2008 and 2023 were followed up, and additional predictors tested. The outcome was violent reconviction within 12 or 24 months. Model performance was evaluated using Harrells C-index, time-dependent AUCs, calibration, and classification metrics at predefined thresholds. ResultsIn temporal validation, FoVOx showed moderate discrimination (AUCs 0.69 and 0.71; C-index = 0.69) and acceptable overall accuracy (Brier <0.11). Calibration was generally good, with mild overestimation at the highest predicted risks (>20%) at 12 months and slight underprediction at 24 months. The updated FoVOx2 model newly incorporated clozapine treatment and additional diagnostic categories. It was associated with improved performance (AUCs 0.77; optimism-corrected C-index = 0.72; Brier 0.06 and 0.09) and achieved good calibration (intercept {approx} 0; slopes 1.03 and 1.05). ConclusionsUpdating risk assessment tools with additional clinical factors can lead to incremental improvement in model performance. Implementing tools should consider clinical utility and impact as next steps.

The COVID-19 pandemic had substantial impact on healthcare systems across the globe, including psychiatric services. Use of electroconvulsive therapy (ECT), a lifesaving intervention for severe mental illness, was reported to have declined during the pandemic in several countries, but nationwide data remain scarce. Using nationwide data from the Danish National Patient Register, we examined all ECT treatments administered in Denmark from September 2019 to May 2025. Weekly treatment numbers were visualized across the three national COVID-19 lockdowns to descriptively assess changes in ECT use. A notable reduction in ECT treatments was observed in the weeks preceding and during the first lockdown (March 11 to May 18, 2020). A post-hoc estimation indicated approximately 1,366 "missed" treatments during the initial pandemic phase in 2020. When these were added to the 27,033 treatments delivered in 2020, the adjusted total approximated annual treatment volumes in 2019 and 2022, suggesting a temporary disruption rather than sustained decline. In contrast, ECT activity during the second and third lockdowns appeared largely unaffected. These findings suggest that ECT provision in Denmark was temporarily reduced during the initial phase of the pandemic but remained resilient thereafter. In the case of a future pandemic, safeguarding timely access to ECT--particularly in early phases-- should be prioritized given its critical role in the treatment of severe mental illness.

BackgroundIn 2020, Oregon became the first U.S. state to establish a regulated framework for adults to access psilocybin services using naturally-derived mushroom products. No studies have examined mental health outcomes among individuals receiving psilocybin in this context. AimsTo evaluate changes in self-reported symptoms of depression, anxiety, and well-being 30-days post-psilocybin session under the Oregon state-regulated model , and document session-related adverse events and doses consumed. MethodsThis was a naturalistic study (March 2024-April 2025) among adults [&ge;]21 years participating in a legal psilocybin services program. Online surveys were completed pre-session, 1-day, and 30-days post-session. Primary outcomes were change in depression, anxiety, and well-being symptoms pre-session to 30-days post-session evaluated using linear mixed-effects models (random effect: timepoint; fixed effects: sex, concurrent psychiatric medication use, age, session dose [total psilocybin equivalents, TPE, mg: psilocybin mg + 1.39 * psilocin mg]). Adverse events (e.g., hallucinogen persisting perception disorder [HPPD]) were assessed at 1-day and 30-days post-session. ResultsParticipants (n=88; median age 43 years; 52% male) were predominantly Oregon residents (53.4%), psychedelic-experienced (64.8%), and concurrently using psychiatric medication (46.6%). All outcomes improved significantly at 30-days post-session (p<0.001), including in sensitivity analyses stratified by concurrent psychiatric medication usage (p<0.001 all outcomes, both groups). Two participants (2.3%) reported symptoms consistent with HPPD at 1-day post-session, but none at 30-days. Mean dose was 27.8 mg (SD 8.2) TPE. ConclusionsPsilocybin sessions delivered under the Oregon regulatory model were associated with clinically meaningful improvements in depression, anxiety, and well-being 30-days post-session, supporting therapeutic effectiveness of legal psilocybin services.

ObjectiveAlthough trauma-focused psychotherapies are effective for posttraumatic stress disorder (PTSD), recovery under routine outpatient conditions remains variable. We examined whether participation in a structured Specialty Care (SC) model integrating clinician specialization, flexible treatment density, and coordinated navigation was associated with accelerated PTSD recovery compared with standard outpatient care. MethodsWe conducted a retrospective matched cohort study (2024-2025) of U.S. adults with active PTSD symptoms (PTSD Checklist for DSM-5 score [&ge;]31) receiving care through an employer-sponsored digital mental health platform. Access to SC was determined by employer benefit design. Propensity-score matching with weighting balanced cohorts on baseline severity and demographics. Primary outcomes included longitudinal PTSD symptom trajectories and time to recovery, remission, and reliable improvement. Secondary outcomes assessed depressive symptoms (PHQ-9). Linear mixed-effects and Cox proportional hazards models were applied. ResultsThe matched sample included 356 SC and 9,409 standard care participants. SC participants received higher treatment intensity, including greater session volume and faster early follow-up, and greater care navigation engagement. SC participation was associated with steeper PTSD symptom decline ({beta} = -1.3 per log-week, p < .001) and a higher likelihood of recovery (hazard ratio = 1.31; 95% CI, 1.10-1.57). At 12 weeks, predicted recovery was 29% in SC versus 23% in standard care. Depressive symptoms improved in both groups, without significant differences in time to categorical recovery. ConclusionsUnder routine outpatient conditions, a structured SC model was associated with accelerated PTSD recovery, suggesting that reorganization of outpatient delivery may improve real-world outcomes.

IntroductionNational trends in youth suicide risk may mask significant regional variations within a country. This article attempts to account for spatio-temporal trends through a comparative analysis across South America and Europe. This paper analyzes the spatiotemporal patterns in suicide mortality among young people (10-29 years) in Argentina, Chile, Spain, and Uruguay during the period 1997-2021. MethodsOfficial data from vital statistics and population censuses of the four countries were analyzed. Spatiotemporal clusters were detected using Poisson-based scan statistics. Sociodemographic characteristics of high-and low-mortality clusters were compared with the rest of each country using Kruskal-Wallis and Wilcoxon tests. ResultsWith the exception of Chile, each country showed the emergence of spatiotemporal suicide clusters extending through 2021. Indicators of social fragmentation and lower socioeconomic status were most consistently associated with the formation of high-risk youth suicide clusters. ConclusionRecent national increases in youth suicide rates appear to be concentrated in specific sub-national regions, underscoring the need to target resources toward improving living conditions and mental healthcare access for young people in these areas.

BackgroundUp to one-third of medical inpatients experience clinically relevant mental distress, yet many remain untreated. Stepped and collaborative care (SCC) models may improve access to mental health care, but predictors of service uptake are unclear. We examined patient- and ward-level predictors of psychosomatic-psychiatric consultation (PPC). MethodsWe analyzed data from SomPsyNet, a stepped-wedge cluster randomized trial targeting SOMatic inpatients across three Swiss tertiary hospitals, to prevent PSYchosocial distress by a care NETwork. Analyses focused on inpatients screening positive for mental distress. Multiple-imputed logistic regressions assessed predictors of four sequential service-use stages: PPC considered, offered, accepted, and received. ResultsAmong 589 distressed patients, 93.9% were offered PPC, 63.1% accepted, and 83.9% of acceptors received PPC, yielding a 50% overall receipt rate. Patients without Swiss citizenship showed higher odds of acceptance (odds ratio [OR]=1.82 [1.10, 3.00]) and eventual receipt (OR=1.62 [1.01, 2.62]). Being in a Geriatric ward facilitated PCC uptake, while patients from gynecology showed reduced progression through the care pathway. Age, gender, income, education, marital status, and living arrangement showed no statistically robust associations. ConclusionsAlmost two-thirds of mentally distressed medical hospital inpatients accepted an offered PPC, indicating high acceptability. About half ultimately received a consultation, highlighting substantial attrition along the SCC pathway. Ward specialty and nationality were key determinants of PPC uptake. These findings suggest that proactive, ward-oriented consultation-liaison models embedded in routine inpatient care may improve timely and equitable access to mental healthcare, including for migrant and minority patients who are otherwise less likely to access such care. HighlightsO_LIPsychosomatic-psychiatric consultation pathway of medically hospitalized inpatients C_LIO_LI63% accepted such a consultation when offered; overall 50% reached receipt. C_LIO_LINon-Swiss nationality increased odds of acceptance (OR 1.8) and receipt (OR 1.6). C_LIO_LIPatients at geriatrics wards showed higher, at gynecology wards lower transitions. C_LIO_LIResults support low-threshold, ward-oriented consultation-liaison models. C_LI

BackgroundImproving access to high-quality community-based crisis care and reducing inpatient admissions are key policy objectives in England, yet evidence on who uses crisis-related services and potential inequalities in access remains limited. AimsTo examine socio-demographic patterns in the use of six crisis-related services in England: 1) Crisis phonelines; 2) Crisis cafes; 3) Crisis Resolution and Home Treatment teams (CRHTs); 4) Voluntary inpatient admissions; 5) Compulsory inpatient admissions under the Mental Health Act 1983 (MHA); and 6) conveyance to a Place of Safety (PoS) by police under section 136 of the MHA. MethodWe conducted a retrospective observational study using the Mental Health Services Data Set between 2021/22 and 2023/24. Adults (aged 18+) using any of the six services were included. A multinomial logit regression model was used to estimate the average marginal effects for age, sex, ethnicity, and area-level deprivation, with robust patient-level standard errors and year fixed-effects. ResultsWithin this population using any crisis-related services, adjusted analysis showed people from several ethnic minority backgrounds were more likely to be compulsorily detained or brought to a PoS by police, and less likely to use CRHTs than White individuals, with largest disparities in compulsory admissions for Black (+15.0 percentage points [pp]) and Asian (+7.3 pp) groups. Compulsory admissions were more common among older adults and men (+1.5 pp). Crisis phonelines were less commonly used by older adults, men (-4.8 pp), and people from Black (-15.6 pp) and Asian (-4.7 pp) backgrounds. Crisis cafes showed more even demographic distributions. Although adjusted differences by deprivation were small (all <1.0 pp), over half of all users lived in the two most deprived quintiles. ConclusionsAmong crisis-related service users, demographic groups at greater risk of coercive care are less likely to access community crisis services. Addressing these disparities could improve access and reduce inequalities.

ObjectivesElectroconvulsive Therapy (ECT) is an effective treatment for bipolar disorder, particularly in severe acute cases or for illness resistant to pharmacotherapy. However, the risk of relapse following ECT is high, necessitating intervention to reduce this risk. Based on findings from ECT studies in unipolar depression and its well-known mood-stabilizing properties, it is likely that lithium treatment may reduce the risk of relapse of bipolar disorder following ECT. Therefore, we conducted a target trial emulation using data from Danish nationwide registers to investigate whether lithium protects against relapse following ECT treatment of bipolar disorder. MethodsPatients discharged from their first psychiatric admission with a primary diagnosis of bipolar disorder between January 1, 2006, and June 1, 2024, who received at least six ECT treatments, were included. Follow-up began two weeks after discharge and continued until relapse, death, one year, or January 1, 2025. Patients were considered allocated to lithium treatment if they redeemed a prescription for lithium within the first two weeks after discharge from the index admission (ECT treatment). The outcome was time to relapse, defined by either psychiatric hospital admission or suicide. Cox proportional hazards regression, adjusted for potential confounders, was used to compare the outcome between patients allocated and not allocated to lithium treatment. ResultsAmong the 574 eligible patients (mean age 41.5 years, 61.3% women), 214 (37.3%) were allocated to lithium treatment and 360 (62.7%) were not allocated to lithium treatment. During follow-up, 56 patients (26.2%) in the lithium group and 135 patients (37.5%) in the non-lithium group experienced a relapse. Lithium treatment was associated with a substantially reduced risk of relapse (adjusted hazard rate ratio, 0.60, 95% CI=0.43-0.84). ConclusionLithium treatment after ECT may reduce the risk of relapse in patients with bipolar disorder. These findings should be followed up by a randomized controlled trial.

BackgroundPredictive models in mental health can identify service users at risk of high-intensity care, enabling proactive interventions. However, false positive predictions may lead to over-medicalisation, inequitable resource use, and stigma. Understanding the factors associated with false positives can improve model interpretation and real-world application. AimsTo evaluate a previously validated prediction model for high-intensity (top decile) service use and identify false positive (FP) vs. true positive (TP) predictions, examining factors across three timeframes: baseline (e.g. demographics and referral information), the prediction period (W1; the first three months after initial mental health service assessment), and the immediate (three month) period following prediction (W2). MethodsOf mental health services users assessed between 2007-2024, 4,174 TP and 17,644 FP predictions were compared. Evaluated covariates included demographics, referral source, service use, diagnoses, medications, and recorded symptoms. Logistic regression was used to identify associations with FP outcomes across the three time periods. ResultsAt baseline, FP predictions were more common among Asian service users, those living with family, and users referred by their GP, whilst TP predictions were associated with voluntary or probation service referrals. During W1, FP predictions were associated with higher community treatment days, crisis attendances, and service users managed in the outpatient setting. TP predictions were associated with antipsychotic use and engagement with multiple care teams. In W2, TP predictions were more likely among service users who remained outpatients, had higher inpatient days, or received multidisciplinary care, and FP more likely among those with substance use, multiple address changes, or ongoing crisis attendances. ConclusionThe approach here to predictive modelling highlights the importance of considering features (here at baseline and W1) which may influence a models accuracy at the point the prediction is communicated, and those subsequent events (W2) which might indicate targets for intervention to prevent the adverse outcome. Both need to be incorporated in clinical interface communications if models are deployed in practice.

BackgroundPoor patient retention and family engagement compromise the effectiveness of coordinated specialty care (CSC) for first-episode psychosis (FEP). This mixed methods study aimed to identify program-level characteristics (CSC fidelity and engagement strategies) associated with patient retention and family engagement in Massachusetts CSC programs. MethodsPrimary outcomes were rates of patient retention and family engagement ([&ge;]1 evidence-based family intervention session), based on CSC program census (October 2022 - September 2023). Quantitative analyses explored program characteristics (EPINET Program-Level Core Assessment Battery) and fidelity ratings (Massachusetts Psychosis Fidelity Scale) as predictors using t-tests or univariate linear regressions. Thematic analysis of program interviews compared patient and family engagement strategies employed by high versus low performing programs. ResultsAcross nine programs, mean patient retention was 86% (range: 58-97%) and family engagement was 40% (range: 12-100%). Higher fidelity to evidence-based services (e.g., individual therapy, family intervention, and supported education/employment) was significantly associated with both outcomes (p<.05; R2 range: .51-.72). Mixed-methods analysis showed that high performing programs used case management-related supports to meet service users practical needs. Factors associated with higher patient retention included having comprehensive intake assessments, provider visits during hospitalization, and periodic treatment reviews. Programs that conducted benefits counseling and proactively recommended family services as standard care had higher family engagement. ConclusionsHigher fidelity CSC programs had better patient retention and family engagement. Case management-related supports addressed treatment barriers. Strategies designed to strengthen therapeutic alliance and goal alignment may promote patient engagement, while family engagement may benefit from proactive recommendation of family intervention.

Background At present, there are no approved pharmacological treatments for people at clinical high risk for psychosis (CHR-P). We sought to assess the acceptability of cannabidiol (CBD): a promising candidate treatment for this population. Methods CHR-P individuals completed a survey which assessed their views on the acceptability of CBD, its expected effectiveness and side effects, and on formulation preferences. Results The sample comprised 55 CHR-P individuals (24.3 years and 69% female). Most (91%) were familiar with CBD, and had previously used cannabis (64%), and around half (42%) had tried over-the-counter CBD. 75% were willing to take CBD as an intervention for mental health problems. Most participants anticipated fewer side effects with CBD than with existing medications, and preferred tablet or capsule formulations over liquids. Discussion CBD is perceived as a highly acceptable treatment among CHR-P individuals.

BackgroundMany people with depression do not respond well to the first antidepressant prescribed. Treatment Resistant Depression (TRD) refers to depression which does not respond to multiple subsequent antidepressant treatments. Identifying TRD in routinely-collected health records is challenging due to limited response-related data. Previous studies have used definitions based on the number of antidepressant switches observed. However, these do not account for other features clinically indicative of treatment resistance, such as augmentation of antidepressants with lithium or antipsychotics and switches between antidepressant classes. This study examined definitions of TRD and their impact on the resulting sample across three cohorts. MethodsAcross the DataLoch, UK Biobank, and Generation Scotland cohorts, we identified cases of depression from primary and secondary care record codes and extracted antidepressant treatment patterns from dispensing/prescribing records (N = 51,283, N = 10,556, and N = 649 respectively). We examined 9 TRD definitions that varied by: the number of switches required (1+, 2+ or 3+ switches), augmentation and between-class switches. We contrasted sample size and characteristics between definitions, and examined factors associated with inclusion versus a reference definition of 2+ switches. ResultsThe reference TRD definition included 10% of depression cases in the routine data collection, but substantially fewer cases (4%) in consented cohorts. More inclusive definitions that required fewer switches or included a between-class switch classified more individuals as TRD, but resulted in a proportionally older, more deprived sample with fewer depression-related health record codes, older age of depression onset, lower symptom severity, and greater use of first-line antidepressants. Requiring more switches (3+ switches) classified fewer individuals as TRD, but resulted in a proportionally younger sample, with more depression-related health record codes, younger age of depression onset, and greater use of antidepressants associated with later in the treatment line (e.g., Tricyclics). Definitions including augmentations resulted in a small increase in sample size without notable change in sample characteristics. ConclusionsTRD is underrepresented in consented cohort studies. A definition of TRD that includes 2+ antidepressant switches or augmented antidepressant treatment as indicators balances sample size with depression severity, while incorporating features from real-world treatment journeys. Key summaryO_LITreatment Resistant Depression (TRD) is often identified in health records using number of switches in antidepressant treatment, but this misses other important indicators of treatment resistance C_LIO_LIWe examined 9 TRD definitions across 3 cohorts, varying in the number of antidepressant switches, the inclusion of augmented treatment, and the inclusion of between-class switches C_LIO_LIA TRD definition that included 2+ switches or augmented treatment balanced sample size and severity C_LI

Individuals with psychiatric disorders have significantly higher mortality rates than the general population. Despite identifying risk factors, few attempts have been made to systematically use this information to stratify mortality risk. To address this gap, we developed and externally validated a risk prediction model using national healthcare and social register data from two countries. Nationwide register data were used to create a Swedish cohort (n=530,201) for model development and a Finnish cohort (n=254,691) for external validation. Participants, aged 15-60 years at assessment, had diagnoses of common mental illnesses (schizophrenia-spectrum disorder, bipolar disorder, depression, or anxiety disorders) made in specialist care. A multivariable logistic regression model assessed predictors of 5-year mortality risk. Model performance was evaluated using discrimination (area under the curve [AUC]) and calibration metrics, including intercept, slope, and visual plots. Internal validation employed bootstrapping. A total of 18,619 (3.5%) Swedish and 11,206 (4.4%) Finnish patients died within 5 years of assessment in secondary care. The model incorporated 25 predictors across four domains: sociodemographic factors, clinical characteristics, somatic comorbidities, and psychotropic medication use. External validation demonstrated excellent discrimination (AUC = 0.803; 95% CI: 0.799-0.807). The higher mortality rate in the Finnish cohort required recalibration of the intercept, and post-adjustment calibration was good (intercept: 0.00; 95% CI: -0.02; 0.02; slope: 0.99; 95% CI: 0.98-1.01). Model findings were translated into a web-based calculator (MortOx) for research, training, and potential clinical use. A transdiagnostic prognostic model based on 25 predictors accurately predicts 5-year mortality risk in mental illness. Linkage to interventions is needed to evaluate clinical impact.

Background and HypothesisClozapine is the only antipsychotic with protective effects against suicide in schizophrenia (SCZ). Newer third-generation antipsychotics (TGA) have better tolerability and modulate serotonin, dopamine, and N-methyl-d-aspartate neurotransmission pathways implicated in suicide. We aimed to investigate the effects of TGAs on suicide in SCZ. MethodsWe searched seven databases up to December 2023 for SCZ studies that reported suicide data. The primary outcome was suicide deaths and attempts; suicidal ideation was added as a secondary outcome. Random effects meta-analyses quantified suicide risk in randomized controlled trials (RCT) while single proportion meta-analyses assessed longitudinal suicide risk in open label extension trials (OLE). For RCTs, sensitivity analyses were conducted and subgroup analyses explored the impact of dose, drug type, and comparator arm. Study ResultsTwenty articles were included; thirteen excluded higher suicide risk participants. Compared to placebo control, TGAs did not significantly change the risk of primary [RR = 0.65, p = 0.38] or secondary [RR = 0.63, p = 0.15] suicide outcomes. Subgroup and sensitivity analyses were not statistically significant. For OLEs, there was a significant increase in the incidence of primary [Ip = 0.004, p = 0.048] and secondary [Ip = 0.024, p = 0.0013] suicide outcomes, but there was marked study heterogeneity. ConclusionThere is no current trial evidence to show that TGAs significantly impact suicide outcomes in SCZ. The signal from OLEs should be interpreted cautiously due to heterogeneity and requires replication. An effective clozapine alternative is needed for suicide prevention in SCZ.

IntroductionSevere mental illness is associated with high mortality rates and cardiovascular disease. Obesity and dysmetabolism associated with antipsychotic treatment comprise modifiable risk factors, which remain undertreated. Interventions such as antipsychotic-switching, lifestyle-interventions and weight-reducing medication have shown varying results indicating a need for a more individualized approach. The Meta-Care Trial aims to assess the effectiveness of a pragmatic, individualized, evidence- and guideline-based cardiometabolic intervention. Methods and analysisMeta-Care is an open-label randomized controlled trial (RCT). Patients between 18-45 years with schizophrenia spectrum disorders or bipolar disorder will be recruited from in- and outpatient Mental Health Services in the Capital Region of Denmark. Inclusion criteria include treatment with antipsychotics and: either i) [&ge;]5% body weight gain or [&ge;]5cm waist circumference increase since initiation of antipsychotic therapy, or ii) a body mass index (BMI) [&ge;]30 kg/m2, or iii) BMI [&ge;]27 kg/m2 and related cardiovascular risk factors. Patients are randomized to a pragmatic, individualized metabolic clinic using evidence- and guideline-based care in a mental health center or standard care. Allocation-ratio is 1:1. The primary outcome is the proportion of patients achieving weight loss [&ge;]5% of initial body weight after 12 months. Secondary and exploratory outcomes cover cardiometabolic risk factors, cognition, personal recovery, and quality of life. Qualitative interviews will explore patient experience and contextual factors. Recruitment started in October 2023 and will include a total of 84 patients. Ethics and disseminationThe Meta-Care trial is funded by The Independent Research Fund Denmark and The Worzner Memorial Fund for Research in Mental Illness. The trial has been approved by the Regional Ethics Committee and Data Protection Agency in the Capital Region of Denmark. Positive, negative, and inconclusive results will be published in scientific peer-reviewed journals, presented at conferences, and dispersed to patient organisations and media. Strengths and limitations- The Meta-Care Trial is the first randomized control trial (RCT) to investigate the effectiveness and acceptability of a pragmatic, individualized metabolic clinic located in a mental health center using evidence- and guideline-based care to treat obesity and cardiometabolic risk factors in patients with severe mental illness - The pragmatic design with limited exclusion criteria and simple outcome measures will generate results that are generalizable to clinical practice - The complex Meta-Care multi-intervention limits inferences of effects explained by specific modifications of pharmacotherapy or lifestyle changes - Potential knowledge exchange from treating personnel in the Meta-Care Trial to caregivers in the standard care group may lead to contamination bias - Although the Meta-Care trial has an open label design, measurements of primary and secondary outcomes will be carried out by blinded assessors

BackgroundDespite widespread recognition of the value of lived experience (LE) involvement in healthcare research and increased LE involvement activity, we lack established implementation methods and instruments for reporting and evaluating impact. We present a protocol for an innovative LE-led Impact Log tool and co-production framework, which may help to address some fundamental barriers to co-production. The Impact Log will be implemented within a five-year multidisciplinary transdiagnostic research project on severe mental illness, the Brain and Genomics Hub of the UKRI Mental Health Platform, and is also designed for wider adaptation and use. Part I presents a short narrative review of literature pertaining to defining, evaluating, and enhancing the impact of co-production, to provide in-depth background and aid future development. Part II presents the Impact Log protocol. MethodsThe Impact Log framework is designed to integrate inclusive and impactful co-production throughout all research stages, and to record and evaluate its impact across three domains using an accessible short form. The three research domains are: design and delivery; interpersonal and environmental aspects; systems and processes. Impact Log design and implementation is led by LE study leads and a specialist advisory panel, who are integrated fully within the wider research team, and all have combined research experience and LE of bipolar or psychotic disorders. All Hub research participants will be offered accessible opportunities for remunerated lived experience input, and there will be outreach to ensure diverse representation, aided by the Hubs charity partners. Data collection and analysis will be LE led and will include iterative analysis to inform continuing development. Diverse formal and informal dissemination throughout the project will maximise wider stakeholder engagement. DiscussionThe potential value of this research is to implement a novel tool and framework for facilitating, recording and evaluating co-production in complex mental health research, which can be adapted for wider use. Strengths in design are LE leadership and cross-cutting LE research integration, incorporation of multiple domains, and a focus on facilitating diversity and inclusion within co-production. Potential limitations for this project and wider adaptation may include limited resources, risk of bias and health challenges. Lay SummaryWe have provided a brief lay summary to help people without a research background understand our project. This article explains our plan to develop and test a new way of understanding how research changes when people with personal experience of a mental health condition are part of the research team. We are a team of mental health researchers and many of us have direct experience of bipolar and psychosis. We work alongside other researchers, including people who might also have worked in mental health services or in charities that provide support. Our research project aims to better understand what is happening in the brain, body, lives and experiences of people who have bipolar and psychosis. Many people believe that research is better when it includes the views of people who have direct experience of the health condition being studied. This is called "lived experience". We have developed a structured approach to make sure that people with lived experience are meaningfully involved in our research team. We have also created a simple tool, called the Impact Log, to record when lived experience members contribute and to help us understand how their involvement influences the research. Finally, we wanted to better understand what other researchers have said about lived experience involvement. We reviewed many published academic studies and reports and brought their findings together in what is called a "narrative review". This review summarises what is already known about the difference lived experience involvement can make in research.

IntroductionMental health problems disproportionately affect marginalised communities rural, coastal, and socioeconomically disadvantaged communities. This is especially true for Norfolk and Suffolk, UK, where anxiety and depression are above national averages, suicide is the leading cause of death among those with mental ill-health, and access to care is poor. These communities are also underserved by research, leaving significant needs unmet. AimsThis project aimed to establish mental health research priorities informed by the views of key stakeholders in Norfolk and Suffolk, including people with lived experience of mental ill-health, members of the public, clinicians, charities, and policymakers. Methods and analysisWe conducted a mixed-methods research-priority-setting exercise involving an online survey (n=156, of whom 64.7% had lived experience) and two in-person prioritisation workshops with people with lived experience (n=10) and health and social care professionals (n=15). Following Delphi principles and guided by the James Lind Alliance approach, the survey asked participants to rate research priority statements across eight mental-health domains using a 3-point Likert scale (0 = low, 1 = moderate, 2 = high). Statements rated as high priority by [&ge;]50% of the respondents were shortlisted for the workshops. During the two-day workshops, participants discussed the shortlisted statements in small groups before voting individually on those they considered most important. Scores were calculated separately for each workshop, then combined to produce a final ranked list of the Top 10 research priorities. EthicsThe University of East Anglias Faculty of Medicine and Health Research Ethics Committee granted ethical approval (reference: ETH2324-2542). ResultsOf the 70 original priority statements, 40 met the threshold for inclusion in the prioritisation workshops. Participants in the two prioritisation workshops identified and agreed on the final Top 10 priorities, spanning youth mental health, physical-mental health integration, access to care, impacts of rural and coastal living, social and health inequalities, health promotion and prevention, and big-data solutions. ConclusionsStakeholders in this study identified local mental health needs and highlighted areas where research is urgently required. These priorities will inform future studies, support policymaking, and guide resource allocation to improve mental healthcare and reduce inequalities in rural and coastal communities. Strengths and limitations of this studyO_LIThis study brought together key stakeholders, including people with lived experience, mental health service providers, local authorities, policymakers, voluntary organisations, academics, and members of the public, to identify mental health research priorities specific to Norfolk and Suffolk populations. C_LIO_LIOur in-depth research priority-setting exercise identified the Top 10 research priority areas to inform future research and service planning. C_LIO_LIWhile the current study included family carers or parents of children with mental health difficulties, future mental health research priority-setting involving children is still needed. C_LI