Clozapine is the antipsychotic of choice for people with treatment-resistant schizophrenia (TRS) but is associated with the uncommon but potentially life-threatening adverse effect of myocarditis. However, there are no criteria for diagnosing clozapine-associated myocarditis (CAM) or global guidelines on detection and risk reduction, or for restarting clozapine after CAM.

To develop criteria for CAM and algorithms for clozapine initiation and clozapine rechallenge after CAM in a multiprofessional consensus process.

We conducted a systematic literature search for cases of clozapine rechallenge following CAM using the PubMed, EMBASE, CINAHL and PsycINFO databases, followed by a multidisciplinary international two-step Delphi consensus process in July and October 2024. The Delphi panel comprised psychiatrists, cardiologists, pharmacists, psychopharmacologists and nurses with expertise on clozapine or myocarditis.

Ninety-three clinicians and academics with experience in prescribing clozapine from six continents participated in the Delphi process. A consensus was reached on a definition of CAM according to modified clinical criteria from the European Society of Cardiology for myocarditis associated with immune checkpoint inhibitors. Titration schemes slower than those given in the Summary of Product Characteristics for clozapine were recommended to minimise CAM risk. Minimum and enhanced requirements for screening and monitoring were developed to account for global perspectives and limited resources in certain healthcare systems, and an approach to clozapine rechallenge was elaborated.

This multidisciplinary project represents the first guidance for CAM and will inform clinicians, other caregivers and patients, as well as facilitating the development of national guidelines on CAM prevention, screening and monitoring and rechallenge after an index episode of myocarditis in individuals taking clozapine.

The COVID-19 pandemic has disproportionately affected patients with severe mental illness (SMI), a vulnerable population with high morbidity and mortality. A UK-based study found reduced vaccination rates in patients with SMI; they therefore need to be prioritised for prevention and disease management.

The objectives were to determine risk factors for vaccine hesitancy, and how best to manage those in patients with SMI, as well as whether our intervention of calling patients for their vaccines had a positive outcome.

Following approval from the Lambeth Directorate of South London and Maudsley (SLaM) NHS Foundation Trust, we investigated COVID-19 vaccination rates inpatients with SMI from a psychosis community service in South London (n=236). Dates of first and second doses were recorded through audit; reasons for refusal of vaccination were noted. Patients were encouraged to take the vaccine. A re-audit was performed after allowing three months. Chi-squared statistical analysis was performed to determine the value of our intervention.

Before the intervention, 143 patients (60.6%) received at least one vaccine. 24 patients (10.2%) received one dose, and 77 (32.8%) were yet to receive any. There was no statistical significance (p=0.1509) between the number of patients who received a vaccine before and after intervention, with 33.1% of patients still remaining unvaccinated.

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There is limited research on perceptions of receiving vaccines in patients with SMI, despite their cost-effectiveness in disease prevention. Even after intervention, 33.1% of patients remained unvaccinated, compared to 6.6% nationally. A lack of knowledge and recommendations from care teams are reasons for hesitancy. Misinformation, conspiracy theories and propaganda can drive people towards refusal. Patients with SMI typically have disadvantages of healthcare inequality, lower levels of education and access to inaccurate information. Patients and their healthcare team should be knowledgeable about vaccine efficacy and side effects. Studies have shown low uptake in the Black/African/Caribbean ethnic group (49.3%, table 3). Reasons include general mistrust in institutions and access barriers. For minority communities, vaccination sites in community centres or places of worship have proven to be effective, providing familiarity.

Patients taking clozapine may have a weaker immune system due to myelosuppression. 24.3% of our patients take this, with many unsure of interactions or side effects. Poorer prognosis means a focussed approach is needed.

Vaccine hesitancy is complex and requires targeted, tailor-made strategies, with consideration for patients who may lack capacity. It is evident from our results that calling patients alone may not be effective. A future multi-modal approach may be necessary to address poor vaccine uptake and opens up avenues to further explore vaccine hesitancy.

None Declared

Altered cerebral blood flow (CBF) has been found in people at risk for psychosis, with first-episode psychosis (FEP) and with chronic schizophrenia (SCZ). Studies using arterial spin labelling (ASL) have shown reduction of cortical CBF and increased subcortical CBF in SCZ. Previous studies have investigated CBF using ASL in FEP, reporting increased CBF in striatum and reduced CBF in frontal cortex. However, as these people were taking antipsychotics, it is unclear whether these changes are related to the disorder or antipsychotic treatment and how they relate to treatment response.

We examined CBF in FEP free from antipsychotic medication (N = 21), compared to healthy controls (N = 22). Both absolute and relative-to-global CBF were assessed. We also investigated the association between baseline CBF and treatment response in a partially nested follow-up study (N = 14).

There was significantly lower absolute CBF in frontal cortex (Cohen's d = 0.84, p = 0.009) and no differences in striatum or hippocampus. Whole brain voxel-wise analysis revealed widespread cortical reductions in absolute CBF in large cortical clusters that encompassed occipital, parietal and frontal cortices (Threshold-Free Cluster Enhancement (TFCE)-corrected <0.05). No differences were found in relative-to-global CBF in the selected region of interests and in voxel-wise analysis. Relative-to-global frontal CBF was correlated with percentage change in total Positive and Negative Syndrome Scale after antipsychotic treatment (r = 0.67, p = 0.008).

These results show lower cortical absolute perfusion in FEP prior to starting antipsychotic treatment and suggest relative-to-global frontal CBF as assessed with magnetic resonance imaging could potentially serve as a biomarker for antipsychotic response.

Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.

The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.

This was a naturalistic study of community patients recommended for clozapine treatment.

Of 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).

These findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.

Total thyroidectomy can be used as a definitive treatment modality for thyrotoxicosis. This study assessed the outcomes of patients treated with surgery at a single secondary care site.

A retrospective cohort study was conducted analysing consecutive patients who underwent thyroid surgery for thyrotoxicosis between 24 November 2000 and 26 April 2019 (n = 595).

Total thyroidectomy was performed in 95.4 per cent of patients. Two-thirds of patients had Graves’ disease histology. Of patients, 22.8 per cent became transiently hypothyroid whilst on levothyroxine (thyroid hormone replacement therapy). Transient and persistent hypocalcaemia was present in 23.3 per cent and 2.8 per cent of patients respectively. Recurrent laryngeal nerve palsy was transient and persistent in 3.6 per cent and 0.3 per cent respectively. Of patients, 2.5 per cent developed post-operative haematomas that required surgical evacuation in the operating theatre.

The overall complication rate for thyroid surgery is higher in thyrotoxic than in euthyroid patients. Compared to other treatment modalities, total thyroidectomy appears to be the most effective, definitive means of managing Graves’ disease.

First-episode psychosis (FEP) is associated with metabolic alterations. However, it is not known if there is heterogeneity in these alterations beyond what might be expected due to normal individual differences, indicative of subgroups of patients at greater vulnerability to metabolic dysregulation.

We employed meta-analysis of variance, indexed using the coefficient of variation ratio (CVR), to compare variability of the following metabolic parameters in antipsychotic naïve FEP and controls: fasting glucose, glucose post-oral glucose tolerance test (OGTT), fasting insulin, insulin resistance, haemoglobin A1c (HbA1c), total-cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides. Standardised mean difference in metabolic parameters between groups was also calculated; meta-regression analyses examined physiological/demographic/psychopathological moderators of metabolic change.

Twenty-eight studies were analysed (1716 patients, 1893 controls). Variability of fasting glucose [CVR = 1.32; 95% confidence interval (CI) 1.12–1.55; p = 0.001], glucose post-OGTT (CVR = 1.43; 95% CI 1.10–1.87; p = 0.008), fasting insulin (CVR = 1.31; 95% CI 1.09–1.58; p = 0.01), insulin resistance (CVR = 1.34; 95% CI 1.12–1.60; p = 0.001), HbA1c (CVR = 1.18; 95% CI 1.06–1.27; p < 0.0001), total-cholesterol (CVR = 1.15; 95% CI 1.01–1.31; p = 0.03), LDL-cholesterol (CVR = 1.28; 95% CI 1.09–1.50; p = 0.002), and HDL-cholesterol (CVR = 1.15; 95% CI 1.00–1.31; p < 0.05), but not triglycerides, was greater in patients than controls. Mean glucose, glucose post-OGTT, fasting insulin, insulin resistance, and triglycerides were greater in patients; mean total-cholesterol and HDL-cholesterol were reduced in patients. Increased symptom severity and female sex were associated with worse metabolic outcomes.

Patients with FEP present with greater variability in metabolic parameters relative to controls, consistent with a subgroup of patients with more severe metabolic changes compared to others. Understanding determinants of metabolic variability could help identify patients at-risk of developing metabolic syndrome. Female sex and severe psychopathology are associated with poorer metabolic outcomes, with implications for metabolic monitoring in clinical practice.

Offspring of parents with major mood disorders (MDDs) are at increased risk for early psychopathology. We aim to compare the rates of neurodevelopmental disorders in offspring of parents with bipolar disorder, major depressive disorder, and controls.

We established a lifetime diagnosis of neurodevelopmental disorders [attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disabilities, specific learning disorders, and motor disorders] using the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version in 400 participants (mean age 11.3 + s.d. 3.9 years), including 93 offspring of parents with bipolar disorder, 182 offspring of parents with major depressive disorder, and 125 control offspring of parents with no mood disorder.

Neurodevelopmental disorders were elevated in offspring of parents with bipolar disorder [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.23–4.47, p = 0.010] and major depressive disorder (OR 1.87, 95% CI 1.03–3.39, p = 0.035) compared to controls. This difference was driven by the rates of ADHD, which were highest among offspring of parents with bipolar disorder (30.1%), intermediate in offspring of parents with major depressive disorder (24.2%), and lowest in controls (14.4%). There were no significant differences in frequencies of other neurodevelopmental disorders between the three groups. Chronic course of mood disorder in parents was associated with higher rates of any neurodevelopmental disorder and higher rates of ADHD in offspring.

Our findings suggest monitoring for ADHD and other neurodevelopmental disorders in offspring of parents with MDDs may be indicated to improve early diagnosis and treatment.

The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.

We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.

The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.

Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.