British Journal of Psychiatry最新文献

Background: 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.

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

Method: 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.

Results: 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.

Conclusions: 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.

Background: 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.

Aims: 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.

Method: 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).

Results: 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.

Conclusions: 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.

Background: 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).

Aims: 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).

Method: 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.

Results: 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%.

Conclusions: 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.

Background: Better knowledge about childhood trauma as a risk factor for psychiatric disorders in young people could help strengthen the timeliness and effectiveness of prevention and treatment efforts.

Aims: To estimate the prevalence and risk of psychiatric disorders in young people following exposure to childhood trauma, including interpersonal violence.

Method: This prospective cohort study followed 8199 adolescents (age range 12-20 years) over 13-15 years, into young adulthood (age range 25-35 years). Data about childhood trauma exposure from adolescents participating in the Trøndelag Health Study (HUNT, 2006-2008) were linked to data about subsequent development of psychiatric disorders from the Norwegian Patient Registry (2008-2021).

Results: One in four (24.3%) adolescents were diagnosed with a psychiatric disorder by young adulthood. Regression analyses showed consistent and significant relationships between childhood exposure to both interpersonal violence and other potentially traumatic events, and subsequent psychiatric disorders and psychiatric comorbidity. The highest estimates were observed for childhood exposure to two or more types of interpersonal violence (polyvictimisation), and development of psychotic disorders (odds ratio 3.41, 95% CI 1.93-5.72), stress and adjustment disorders (odds ratio 4.20, 95% CI 3.05-5.71), personality disorders (odds ratio 3.98, 95% CI 2.70-5.76), alcohol-related disorders (odds ratio 3.28, 95% CI 2.06-5.04) and drug-related disorders (odds ratio 4.67, 95% CI 2.87-7.33).

Conclusions: These findings emphasise the importance of integrating knowledge about childhood trauma as a potent risk factor for psychopathology into the planning and implementation of services for children, adolescents and young adults.

Background: 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.

Aims: 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.

Method: 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.

Results: 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.

Conclusion: 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.