The British Journal of Psychiatry

BackgroundA high proportion of autistic people receive off-license antipsychotic medication, often in the absence of a mental illness, primarily for behaviours that challenge, which is a public health concern. Although meta-analyses have been published recently, there is a lack of a comprehensive network meta-analysis to inform clinicians about the relative efficacy and safety of antipsychotic medications. AimsTo conduct a network meta-analysis of available RCTs of antipsychotic medications involving autistic participants to assess the relative efficacy of different antipsychotics and their adverse effects. MethodWe searched seven databases and hand-searched ten relevant journals. Two authors independently screened titles, abstracts, and full papers, extracted data, and assessed their quality. ResultsWe analysed data from 22 RCTs involving 1562 autistic people. The largest mean difference with 95% confidence interval in the Aberrant Behaviour Checklist-Irritability (ABC-I) score compared with placebo was from the combined intervention with risperidone and parent training: -11.16 (-15.13, -7.18), followed by risperidone: -7.59 (-9.22, -5.95), and aripiprazole: -5.59 (-7.18, -4). The largest effect on Clinical Global Impression-Improvement (CGI-I) scores was from risperidone, 7.65 (2.17, 27.04), followed by aripiprazole, 7.02 (1.92, 25.72), compared with placebo. Risperidone (4; 1.57, 10.21) and aripiprazole (2.77; 1.20, 6.39) had significantly higher odds ratios for adverse effects, but aripiprazole showed the least weight gain. ConclusionsCombined parent training and risperidone followed by risperidone and aripiprazole showed the best effects on the ABC-I score, whereas risperidone and aripiprazole showed the greatest effect on the CGI-I score. However, risperidone and aripiprazole showed significantly increased adverse effects.

BackgroundClozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics. AimsTo investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation and intensive care treatment, and death, among patients taking antipsychotics with schizophrenia-spectrum disorders. MethodUsing data from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics at the time of the COVID-19 pandemic in the UK, and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores. ResultsIn the 157 individuals who developed COVID while on antipsychotics, there were 44 COVID-related hospitalisations, 13 COVID-related intensive care treatments and 13 deaths of any cause during the follow-up period. In the unadjusted analysis, there was no significant association between clozapine and any of the outcomes and there remained no associations following adjusting for the confounding variables. ConclusionsIn our sample of patients with COVID-19 and schizophrenia-spectrum disorders, we found no evidence that clozapine treatment puts patients at increased risk of hospitalisation, intensive care treatment or death, compared to any other antipsychotic treatment. However, further research should be considered in larger samples to confirm this. Conflict of interestRDH has received research funding from Roche, Pfizer, Janssen, and Lundbeck. DFF has received research funding from Janssen and Lundbeck. JHM has received research funding from Lundbeck. JTT has received research funding from Bristol-Meyers-Squibb. RS declares research support in the last 36 months from Janssen, GSK and Takeda. Ethics statementThe research was conducted under ethical approval reference 18/SC/0372 from Oxfordshire Research Ethics Committee C.

INTRODUCTIONSince the start of the COVID-19 pandemic inequalities around child mortality are likely to have increased. Suicide in young people has risen in many countries over the last 10 years, and suicide in particular may have been expected to increase over the course of the lockdown, as rates of mental health needs increased. AIMThe aim of this work was to report any changes, and characteristics of children dying of suicide in England, before, and during the COVID pandemic. METHODSChild deaths from suicide, reported to the National Child Mortality Database, occurring between 1st April 2019 and 31st March 2023 were identified, and linked to demographic data, death-review data and routine Hospital Episodes Statistics (HES) data (preceding the death). Routine HES data was used to identify mental health disorders and self-harm events. Temporal trends across the time period were quantified, alongside any changes in sociodemographic characteristics. Using Case-Cross Over methodology, we investigated the relative risk of suicide, after recent HES-coded events. RESULTSIn total there were 498 deaths likely due to suicide, during the 4 year period. Overall risk of death by suicide was 14.31 (13.08-15.63) per 1,000,000 CYP per year. Overall, there was little evidence that risk (p=0.863) or method (p=0.199) changed over the period (p=0.863). There was evidence that the relationship between deprivation and suicide risk was different between ethnic groups (both p<0.001), with decreasing deprivation associated with increasing risk of suicide in white children (IRR 1.12 (1.03-1.21)), and decreasing risk in Asian (IRR 0.52 (0.41-0.65)), Black (IRR 0.31 (0.21-0.44)) and Mixed/Other ethnicity (IRR 0.73 (0.60-0.89) children. Only a recorded diagnosis of self-harm was more common before the death than in the preceding control periods (OR 8.99 (4.27-18.94)). CONCLUSIONIn England, suicide rates do not appear to be increasing, and the methods of suicide remain static. However, the role of deprivation and suicide risk appears to be different between children of different ethnic groups, and while hospital admission and a recorded diagnosis of mental health disorder does not appear to predict suicide in the subsequent month, there was a strong association with self-harm events.

Background Little is known about the provision of diagnoses to young people with mental health disorders. We investigated diagnosis provision by NHS mental health services, focusing on 17-year-olds in South London between 2009-2024, and compared with estimated disorder prevalence. Methods To examine diagnosis provision in the population, we extracted diagnosis data from records of the NHS mental healthcare provider serving South London, using the Maudsley Biomedical Research Centre Clinical Record Interactive Search application; we then compared these data with the corresponding population size, obtained from the Office for National Statistics. To assess diagnosis provision in those with mental health disorders, we compared diagnosis data with the number of young people estimated to have met criteria for a disorder, derived from epidemiological interview data collected in the Environmental Risk (E-Risk) Longitudinal Twin Study and weighted according to characteristics of 17-year-old South Londoners. To assess diagnosis provision in those with mental health disorders within health services, we compared diagnosis data with the number estimated to have met criteria for a disorder and used any health service for their mental health, again derived from weighted E-Risk Study data. Findings Of 17-year-olds from South London in 2009-2024, 4.0% (n=8,958/223,404) had a diagnosis in mental health records during the previous year. This diagnosis provision covered <1 in 16 of those estimated to have had a mental health disorder, and <1 in 4 of those estimated to have also used health services. Diagnosis provision was lower in girls than boys and in young people with Black/Asian/Mixed/Other ethnicity than those with White ethnicity, in those estimated to have had a mental health disorder and used health services. Interpretation These findings demonstrate gaps and biases in mental health diagnosis provision for young people, including within health services, and reveal the imperative need to strengthen young people's mental healthcare.

BackgroundEvidence suggests that individuals with intellectual disabilities may be at increased risk of affective and non-affective psychotic disorders. However, studies so far have been limited by small and selected samples. Moreover, the role of early life trauma, a key environmental risk factor for psychosis, in the potential associations is unknown. MethodsUsing data from Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, we investigated the associations between ID, psychotic disorders, and psychotic experiences in adulthood, and assessed the potential mediating role of trauma in childhood. Individuals with intellectual disabilities were identified using a multisource measure utilising cognitive, functional, and diagnostic indicators from ALSPAC combined with health and administrative records. Psychotic disorder clinical diagnoses were extracted through linkage to primary care records. Psychotic experiences were assessed at ages 18 and 24 using the semi-structured Psychosis-Like Symptoms interview (PLIKSi). Traumatic experiences between ages 5 and 11 were assessed with questionnaires and interviews administered to children and parents at multiple ages. Multiple imputation was performed across all analyses to mitigate potential bias due to missing data. FindingsThe maximum sample after multiple imputation was 9,407. We found evidence of associations between intellectual disabilities and psychotic disorders (OR= 4.57; 95%CI: 1.56-13.39). Evidence was weaker in the case of psychotic experiences (OR=1.63; 95%CI: 0.93-2.84). There was some evidence suggesting a potential mediating role of traumatic experiences in the associations between ID and psychotic experiences (OR= 1.09; 95%CI: 1.03-1.15). Evidence was less consistent in the case of psychotic disorders. Complete records analyses yielded comparable estimates. InterpretationIntellectual disabilities are associated with psychotic disorders and experiences in young adulthood. Further research into the contribution of trauma could shape current intervention strategies for psychotic disorders in this population. FundingThe Baily Thomas Charitable Fund

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.

BackgroundSchizophrenia spectrum disorders are associated with higher risk of unemployment for the individual. Antipsychotic usage is linked to less risk of relapse, fewer hospitalisations and lower rates of mortality. This study investigates the use and discontinuation of antipsychotics in individuals with psychosis in relation to employment and other functional outcomes. MethodsUsing Danish nationwide registers, we identify individuals aged [&ge;]18 with first-time nonaffective psychosis diagnosis (ICD-10 F20-F29) during 1995-2024. Antipsychotic exposure is categorised as continuous use ([&ge;]80% coverage), intermittent use (20-80%), sustained discontinuation (<20%), or no use. Functional outcomes include: employment status, benefit code, hospital readmission. Within-subject analyses use each individual as their own control, with time-varying covariates and 6-, 12-, and 24-month lagged effects. Models adjust for treatment sequence, time since diagnosis, and concurrent psychotropic medication use. HypothesesO_LIFor individuals with schizophrenia spectrum disorders, periods of antipsychotic treatment will be associated with higher likelihood of O_LIemployment/ education/training and C_LIO_LIindependent living, relative to periods without such treatment. C_LI C_LI Exploratory hypothesesPeriods of long acting injectables or clozapine treatment will be associated with higher likelihood of employment/ education and independent living relative to periods with other antipsychotic treatment.

BackgroundThe trends in sedative use have varied in recent years. Benzodiazepines and z-drugs are indicated for anxiety and sleep disorders, but should be limited to short term use. The aim of this study is to examine trends and patterns in sedative prescribing in Ireland between 2014 and 2022, as well as comparing trends between Ireland and England within the same period. MethodsMonthly data on medicines prescribed and dispensed in primary care on the means-tested General Medical Services (GMS) scheme in Ireland was used. Volumes of prescribed benzodiazepine and z-drug use and patterns of prescribing, including initiations, discontinuations, chronic use, and high-risk prescribing were summarised per year. Other sedating agents (sedating antihistamines, antidepressants, and antipsychotics) were also analysed. Volume of use outcomes were compared with NHS data from England for the same period. ResultsThe rate of benzodiazepine and z-drug dispensings per 1,000 GMS population decreased by 4%, from 1,531 in 2014 to 1,474 in 2022. T By comparison in England, there was a steeper decrease of 27% in the dispensing rate and the level of use was substantially lower, falling from 288 dispensings per 1,000 population in 2014 to 210 in 2022. In Ireland, dispensing rates were highest amongst women and older age groups. High-risk dispensings of benzodiazepines and z-drugs decreased over the study period DiscussionDespite decreases in benzodiazepine and z-drug dispensings, rates remain high in Ireland and may suggest a need for enhanced availability of non-pharmacological interventions, and improved education and deprescribing support for healthcare professionals. Statement of SignificanceThe use of benzodiazepines and z-drugs has decreased in many populations in recent years, while prescribing of other sedatives has increased. In Ireland, comparatively higher levels of prescribing have been previously identified. Describing and quantifying medication use is important to monitor medication safety at the population level, however this can be complex and therefore a range of indicators are needed to capture differences. The findings of this study suggest that benzodiazepine and z-drug dispensing is decreasing in Ireland, including high-risk dispensings and dispensings to older age groups. However, in comparison to England, dispensing rates remain high and suggest a need for enhanced availability of non-pharmacological services and interventions, as well as improved education and deprescribing support for healthcare professionals.

BackgroundPsychosis-like experiences (PLEs) are common and associated with mental health problems and poorer cognitive function. There is limited longitudinal research examining associations between cognition and PLEs in early adulthood. AimsWe investigated the association of PLEs with different domains of cognitive function, using cross-sectional and longitudinal observational, and Mendelian randomisation (MR) analyses. MethodParticipants from the Avon Longitudinal Study of Parents and Children (ALSPAC) completed tasks of working memory at age 18 and 24, and tasks of response inhibition and facial emotion recognition at age 24. Semi-structured interviews at age 18 and 24 established presence of PLEs (none vs. suspected/definite). Cross-sectional and prospective regression analysis tested associations between PLEs and cognition (N=3,087 imputed sample). MR examined causal pathways between schizophrenia liability and cognition. ResultsThe fully adjusted models indicated that PLEs were associated with poorer working memory performance (cross-sectional analyses: b=-0.18, 95% CI -0.27 to -0.08, p<0.001; prospective analyses: b=-0.18, 95% CI -0.31 to -0.06, p<0.01). A similar pattern of results was found for PLEs and response inhibition (cross-sectional analyses: b=7.29, 95% CI 0.96 to 13.62, p=0.02; prospective analyses: b=10.29, 95% CI 1.78 to 18.97, p=0.02). We did not find evidence to suggest an association between PLEs and facial emotion recognition. MR analyses were underpowered and did not support observational results. ConclusionsIn young adults, PLEs are associated with poorer concurrent and future working memory and response inhibition. Better powered genetically informed studies are needed to determine if these associations are causal.

BackgroundAntipsychotic medications are recommended for managing schizophrenia spectrum disorders, yet their long-term effects on functional recovery remain unclear. Existing evidence is conflicting, often derived from between-subject comparisons vulnerable to confounding by indication. MethodsWe conducted a nationwide register-based cohort study of 65,630 individuals with incident schizophrenia spectrum disorders in Denmark (1998-2023). We modelled antipsychotic exposure against productive engagement (employment or education). We employed two distinct analytical approaches to separate causal from prognostic associations: (1) Within-subject stratified Cox models with time-varying covariates, where patients served as their own controls to eliminate time-invariant confounding; and (2) Fine-Gray competing risks models using a between-subject design with baseline exposure, accounting for mortality and emigration. FindingsOver 26.9 million person-weeks, the overall productive engagement rate was 48.2%. Integration of hospital pharmacy data revealed a 6.1% exposure misclassification bias in previous studies relying solely on community records. The primary within-subject analysis revealed significant temporal heterogeneity: medication use was associated with reduced engagement rates in the acute (0-2 years: HR 0.908) and consolidation phases (2-5 years: HR 0.946), but reversed to a positive association in the maintenance phase (5+ years: HR 1.019). In contrast, the between-subject Fine-Gray model yielded a null result (SHR 1.002, 95% CI 0.988-1.015), failing to detect these phase-specific dynamics. InterpretationWithin-subject modelling reveals that antipsychotic treatment involves a functional trade-off: it is associated with a transient reduction in engagement rates during the early consolidation phase (2-5 years), followed by stabilisation and potential benefit in the maintenance phase (5+ years). The null result in standard between-subject (Fine-Gray) analysis likely reflects residual confounding by indication and exposure misclassification, highlighting the necessity of within-person designs to unmask the true stage-specific impact of pharmacotherapy on vocational recovery. FundingNone directly for this study. Danmarks Nationalbank funded the research visit that facilitated this collaboration.

BackgroundDespite considerable interest in the consequences of benzodiazepine and benzodiazepine-related Z-drug (BZDR) use, little is known about whether and how initiation of BZDR treatment contributes to the development of alcohol- and drug-related problems. AimTo examine the association of incident BZDR dispensing with subsequent development of broadly defined alcohol- and drug-related problems. MethodsThis nationwide register-based study included demographically matched and co-twin control cohorts. Among all Swedish residents aged [&ge;]10 years and BZDR-naive by 2007, 960,430 BZDR-recipients with incident dispensation in 2007-2019 and without any recorded pre-existing substance-related conditions were identified and matched (1:1) to nonrecipients from the general population. Twin BZDR-recipients (n=12,048) were linked to 12,579 unexposed co-twins. Outcomes included alcohol and drug use disorders, poisoning, deaths, and related suspected criminal offences. Flexible parametric survival models estimated outcome risks across up to 14 years of follow-up. ResultsIn the demographically matched cohort (60% women, median age at BZDR initiation 51 years), incidence rates in BZDR-recipients and nonrecipients (per 1000 person-years) were 5.60 vs 2.79 for alcohol-related and 4.15 vs 1.23 for drug-related problems, respectively. In fully-adjusted models, relative risks were increased for alcohol- and drug-related problems (adjusted hazard ratio [95% confidence interval]: 1.56 [1.53-1.59] and 2.11 [2.05-2.17], respectively). The risks persisted within the co-twin comparison, different follow-ups, and all additional and sensitivity analyses. ConclusionsBZDR initiation was associated with a small but robust increase in absolute and relative risks of developing alcohol- and drug-related problems. The findings contribute to evidence base for making decisions on BZDR treatment initiation.

BackgroundSchool closures used to contain the COVID-19 pandemic may have negative impacts on students mental health but credible evidence is scarce. Sweden moved upper-secondary students to remote learning but, as the only country in the OECD, kept schools at lower levers open throughout the pandemic. MethodsUsing nationwide register data, we estimate the difference in the use of mental healthcare services between upper- and lower-secondary students during the pandemic, and relate this to the same group difference prior to the pandemic. For the main analysis, this difference-in-difference approach is applied to the period April-June 2020 when upper-secondary schools were fully closed. We also study the periods July-December 2020 when upper-secondary schools were largely open, and January-March 2021 when they were partially closed. We study the impact on all contacts with hospitals and specialist psychiatric care due to mental and behavioral disorder, as well as prescriptions for antidepressants, insomnia, and ADHD drugs. FindingsCompared with expected rates, the use of mental healthcare services among upper-secondary students fell by -3.71 [CI95 -5.52 to -1.91] cases per 1000 during April-June 2020, largely due to a reduction in depression and anxiety-related diagnoses (-1.49; CI95 [-2.36 to -0.63]) and prescriptions (-1.80; CI95 [-2.93 to -0.68]). This reduction in the use of mental healthcare services corresponds to a 4.36% CI95 [-6.47 to -2.25]) decrease compared to the level prior to the pandemic. The decrease compared to expected rates persists through July-December 2020 (-3.55%; CI95 [-5.38 to -1.71]) and January-March 2021 (-5.23%; CI95 [-7.24 to -3.21]). The reduction is stronger among students in the 2nd (-5.06%; CI95 [-8.02 to -2.09]) and 3rd (-4.86%; CI95 [-8.19 to -1.53]) year of upper-secondary school. The decrease is concentrated to students who was not in contact with mental healthcare services earlier in the academic year (-16.70%; CI95 [-22.20 to -11.20]). The relative reduction is largest for unplanned care (-13.88%; CI95 [-19.35 to -8.42]) and care at emergency units (-18.19%; CI95 [-26.44 to -9.92]). InterpretationClosing upper-secondary schools in Sweden reduced use of mental healthcare services. There is no indication of this being due to reduced accessibility. In a setting with no strict lockdown, moving to online teaching for a limited period did not worsen mental health among students in upper-secondary schools.

ObjectiveCognitive impairment occurs in antipsychotic-naive first-episode psychosis (FEP), but antipsychotics confound interpretation of the longitudinal course of cognition. The primary aim was to disentangle the effects of illness from antipsychotics on cognition over the first 6-months of FEP treatment. MethodsRandomised, triple-blind placebo-controlled trial (Staged Treatment and Acceptability Guidelines in Early Psychosis; STAGES), where cognition was a secondary outcome. Antipsychotic-naive FEP patients were allocated to receive risperidone/paliperidone (N=38) or placebo (N=40) in addition to intensive psychosocial therapy for 6-months. A healthy control group (N=42) was also recruited. A cognitive battery assessing attention, working memory, processing speed, verbal fluency, cognitive control and verbal paired-associate learning and memory was administered at baseline and 6-months. Twelve- and 24-month follow-up was also conducted. ResultsOver the 6-month trial period, cognitive performance remained stable (working memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. The exception was for verbal paired-associate learning and memory, where a significant group-by-time interaction was observed. The placebo and healthy control groups improved, and the medication group deteriorated on immediate paired-associate recall (p=0.039) and delayed cued recall (p=0.005); effect sizes were medium-to-large. Findings were similar when only trial completers were included in the analysis. ConclusionsRisperidone/paliperidone may cause progression of memory impairment in the early months of FEP. Replication is needed in confirmatory trials. The findings support the need for careful consideration of the risks and benefits of various antipsychotics and the importance of accounting for their cognitive effects in longitudinal research. Trial registrationAustralian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/ ACTRN12607000608460).

BackgroundIdentify risk factors for repeat hospitalisation involving self-harm by Aboriginal and non-Aboriginal people in the Northern Territory (NT), Australia. MethodsA retrospective cohort study of hospitalisations involving suicidal ideation and/or self-harm between 1 July 2001 and 31 December 2013 followed up to 31 December 2018. Survival analyses identified demographic and clinical characteristics associated with repeat hospitalisation involving self-harm. ResultsThe risk of repeat hospitalisation involving self-harm was higher (HR 1.39; 95% CI: 1.22-1.59) amongst Aboriginal (n=2,304) than non-Aboriginal people (n=2,087). Compared to suicidal ideation only, a higher risk of repetition was observed for any self-harm method (aHR: 1.71; 95% CI: 1.37-2.12) amongst Aboriginal people and self-poisoning only (aHR: 1.45; 95% CI: 1.13-1.85) amongst non-Aboriginal people. Previous substance misuse was associated with a higher risk of repeat hospitalisation involving self-harm for Aboriginal (aHR: 1.7; 95% CI: 1.38-2.1) and non-Aboriginal (aHR: 1.6; 95% CI: 1.14-2.25) people. For non-Aboriginal people, several mental health diagnoses were associated with higher risks of repetition. LimitationsThe use of routinely collected administrative data limits analysis to only coded diagnoses and does not represent the full burden of self-harm and suicidal ideation in hospitals. ConclusionThe similarities and differences in long-term risk of repeat hospitalisation involving self-harm between Aboriginal and non-Aboriginal people pose distinct challenges for clinical management and prevention. The results emphasise the importance of comprehensive psychosocial assessment to properly understand the interplay of individual and contextual influences and highlights the need to better understand the availability and effectiveness of culturally tailored clinical interventions and community-based solutions.

BackgroundAntipsychotics are central to relapse prevention in schizophrenia, but longer-term use is associated with adverse effects that often prompt dose reduction or discontinuation. Although relapse risk increases after discontinuation, the nature of relapse remains unclear. Specifically, it is uncertain whether relapse reflects re-emergence of underlying illness or pharmacological withdrawal. MethodsWe analysed longitudinal symptom data (Positive and Negative Syndrome Scale; PANSS) from 417 individuals with schizophrenia who experienced relapse post-stabilization in five randomized, double-blind, placebo-controlled discontinuation trials of oral and long-acting injectable (LAI) paliperidone. Latent class mixed modelling was used to identify distinct trajectories of symptom change preceding relapse. FindingsTwo latent classes of relapse were identified: rapid and delayed onset. Rapid relapse was associated with more severe positive, negative, and cognitive symptoms at relapse. The proportion of individuals experiencing rapid relapse did not differ between those randomized to placebo (treatment discontinuation) versus treatment continuation in either LAI (p=0.119) or oral trials (p=0.949). No consistent increase in withdrawal-like symptoms (e.g. anxiety, agitation, depression) was found in discontinuation compared to continuation groups. Across formulations, individuals with rapid relapse had significantly higher baseline PANSS scores than those with delayed relapse (p<0.001). InterpretationRelapse following antipsychotic discontinuation follows at least two distinct trajectories that are not specific to treatment withdrawal. The comparable proportions of rapid and delayed relapse trajectories between discontinuation and continuation groups, together with the absence of a distinct symptom profile at relapse, does not support pharmacological withdrawal as a common mechanism of relapse. Instead, higher baseline symptom severity in those who experience rapid relapse may reflect pre-existing vulnerability and/or trial-related measurement artefacts related to baseline symptom rating and trial inclusion criteria. This emphasizes the clinical importance of risk stratification and individual monitoring, and challenge the assumption that relapse risk can be meaningfully reduced through dose tapering strategies alone.

Background. There is growing evidence to suggest a clinically significant overlap between autism spectrum conditions and psychotic disorders. Preliminary evidence suggest that autism diagnoses and autistic traits are associated with poorer outcomes following a first episode of psychosis. Methods. This study used data from the Cambridgeshire and Peterborough National Health Service Foundation Trust (CPFT) Research Database to examine clinical outcomes in autistic and non-autistic people following a first episode of psychosis. We describe patterns of community and inpatient service use, using descriptive statistics , Cox regression, binomial logistic regression, and negative binomial regression. Results. Data from 282 autistic and 7127 non-autistic people with psychosis were analysed. Autism was associated with greater community service use (use of mental health emergency lines, mental health detentions by police), as well as greater likelihood of psychiatric hospital admission (adjusted hazard ratio 1.34, 95% confidence interval 1.05 -1.7, p<0.05) and longer inpatient stays (median 111 versus 48 days, p<0.0001). Learning disability played a significant role in the utilisation of community and inpatient services, with lower rates of community service use but longer inpatient admissions. Conclusions. This study indicates a differing pattern of service use between autistic and non-autistic people following psychosis that warrants further research into how best to support autistic people with psychosis.

BackgroundA study conducted in Norway showed that the association between pupil mental health diagnoses and educational attainment has weakened over time. One possible explanation is that earlier detection of mental health problems in recent years has facilitated earlier treatment, intervention, and educational support that might improve academic outcomes. We investigated whether the weakening association between mental health and attainment could be replicated in England, and explained by earlier age at first diagnosis. MethodsThis was a secondary longitudinal data analysis of de-identified records from a secondary mental healthcare provider in England, which have been linked to the Department for Educations National Pupil Database. We included n=149,841 pupils residing in South East London, born 1993-2003, who completed their end-of-school exams 2009-2019. The main exposure variables were ADHD and internalising disorder diagnosis. In linear regressions, we investigated their associations with Year 11 attainment (typically assessed age 15-16 years), whether this was modified by birth year, and the role of age at first diagnosis. ResultsOn average, ADHD (n=844, 0.6%) and internalising disorder (n=2,523, 1.7%) were associated with lower Year 11 attainment. However, significant interactions between diagnosis and birth year suggested that pupils with these disorders showed increases in standardised exam scores over successive birth cohorts, resulting in a closing attainment gap over time. While age at first diagnosis became younger over the period, this did not confound the observed associations. ConclusionsWe replicated findings from Norway that suggest a narrowing attainment gap between those with and without ADHD and internalising disorder diagnoses. Building on this, we ruled out earlier age of diagnosis as a possible explanation for this phenomenon. With administrative data research growing internationally, we are increasingly able to replicate mental health and education trends in different countries, opening more opportunities for international collaboration.

BackgroundDiagnostic categories within the psychosis spectrum are widely used in clinical practice, however psychosis may occur on a continuum. Therefore, we explored whether the continuous distribution of psychotic symptoms across categories is a function of genetic as well as environmental risk factors, such as polygenic risk scores (PRSs) and cannabis use. MethodsAs part of the EU-GEI study, we genotyped first episode psychosis patients (FEP) and population controls, for whom transdiagnostic dimensions of psychotic symptoms or experiences were generated using item response bi-factor modelling. Linear regression was used, separately in patients and controls, to test the associations between these dimensions and schizophrenia (SZ) PRSs, as well as the combined effect of SZ-PRS and cannabis use on the positive symptom/experience dimensions. ResultsSZ-PRS was associated with negative (B=0.18; 95%CI 0.03 to 0.34) and positive (B=0.19; 95%CI 0.03 to 0.36) symptom dimensions in 617 FEP, and with all the psychotic experience dimensions in 979 controls. The putative effect of SZ-PRS on either symptom or experience dimensions was of a small magnitude. Cannabis use was additionally associated with the positive dimensions both in FEP (B=0.31; 95%CI 0.11 to 0.52) and in controls (B=0.26; 95%CI 0.06 to 0.46), independently from SZ-PRS. ConclusionsWe report two validators to the latent dimensional structure of psychosis. SZ risk variants and cannabis use independently map onto specific dimensions, contributing to variation across the psychosis continuum. Findings support the hypothesis that psychotic experiences have similar biological substrates as clinical disorders.

The COVID-19 pandemic is likely to have had a particularly high impact on the health and wellbeing of people with pre-existing mental disorders. This may include higher than expected mortality rates due to severe infections themselves, due to other comorbidities, or through increased suicide rates during lockdown. However, there has been very little published information to date on causes of death in mental health service users. Taking advantage of a large mental healthcare database linked to death registrations, we describe numbers of deaths within specific underlying-cause-of-death groups for the period from 1st March to 30th June in 2020 and compare these with the same four-month periods in 2015-2019. In past and current service users, there were 2561 deaths in March-June 2020, compared to an average of 1452 for the same months in 2015-19: an excess of 1109. The 708 deaths with COVID-19 as the underlying cause in 2020 accounted for 63.8% of that excess. The remaining excess was accounted for by unnatural/unexplained deaths and by deaths recorded as due to neurodegenerative conditions, with no excess in those attributed to cancer, circulatory disorders, digestive disorders, respiratory disorders, or other disease codes. Of 295 unexplained deaths in 2020 with missing data on cause, 162 (54.9%) were awaiting a formal death notice (i.e. the group that included deaths awaiting a coroners inquest) - an excess of 129 compared to the average of previous years, accounting for 11.6% of the excess in total deaths.

BackgroundPeople with severe mental illnesses (SMIs) are three times more likely to smoke than the wider population, contributing to widening health inequalities. Here we report the long term [3 year] outcomes for the SCIMITAR+ trial (ISRCTN72955454), which compared usual care to a bespoke smoking cessation package. MethodsWe recruited 526 heavy smokers with bipolar illness or schizophrenia who were randomly allocated to a bespoke smoking cessation intervention (n=265) or to usual care (n=261) between October 2015 and December 2016. We measured long-term quitting by carbon monoxide-verified smoking status at 3 years post randomisation, and a range of secondary outcomes. Results261 of the original 526 were followed up. 209 participants (80.1% of followed-up; 39.7% of randomised) could be defined as a smoker or non-smoker for the 36-month primary analysis. Forty-three participants (16.5% of 261) were determined to be a non-smoker via self-reporting and CO confirmation; 21 in the intervention arm (16.3% of 129; 19.6% of those who provided both self-reported and CO measure) and 22 in the control arm (16.7% of 132; 21.6% of those who provided both self-reported and CO measure) - adjusted OR of 0.89 (95% CI 0.45, 1.77, p = 0.74). For secondary outcomes, there was no sustained between group difference in reduction in nicotine dependence (measured using the Fagerstrom Test for Nicotine Dependence) or motivation to quit. Some short-term improvements in physical health (measured by the Short Form 12) were present at 36 months. ConclusionsA bespoke intervention represents the model for care for mental health services in the UK, but long term quit rates cannot be assumed. Sustained attention to smoking and relapse is likely to be needed to ensure that short term gains are maintained. The certainty of these results is tempered by loss to follow up and low statistical power. FundingThis study was funded by NIHR Health Technology Assessment Programme (Project number 11/136/52) Plain English SummarySmoking rates are very high amongst people who use mental health services. This makes a significant contribution to health inequalities and reduced life expectancy. Earlier research has shown that smoking cessation services are effective when the specific needs of people with mental ill health are taken into account. This forms the basis of guidelines issued by the National Institute for Health and Care Excellence. In this study we looked at the longer-term impact of an intervention to help people to quit smoking. At three years under half of the people who took part in the original study were able to provide information on their use of tobacco. The rates of smoking were similar between people who received the intervention three years ago, and those who received only usual care. Since we already know that the intervention is effective in helping people to quit in the short term, it would be prudent to ensure that people continue to be offered care to help them to quit if they are at risk of relapse. The longer-term impact of a brief intervention on longer term quit rates cannot be assumed, since the strength of this conclusion is limited because we were only able to follow up under half of the people who took part in the study. Further research is needed into the optimum way in which the health benefits of quitting can be sustained in the longer term.