Aims: Antipsychotic medications are essential in treating patients with severe mental illness (SMI), but they are associated with rapid weight gain, significantly increasing the risk of cardiovascular disease and diabetes. These physical health complications contribute to reduced life-expectancy and development of preventable physical health conditions. The NIHR-RESOLVE study (REF:HSDR131871) explored non-pharmacological interventions for antipsychotic induced weight gain, and highlighted the urgent need for a structured, preventative pathway to support patients at risk.

Fragmentation between physical and mental health services, can leave patients with SMI without adequate physical health support. Despite national guidelines recommending annual physical health checks, interventions often come too late, typically after significant weight gain has already occurred. Additionally, stigma surrounding weight gain exacerbates mental health difficulties.

Methods: IMPLeMENT, an impact study funded by Aston University, facilitated three online workshops, and one in-person event to co-produce a person-centred preventative pathway to manage antipsychotic-induced weight gain. In collaboration with The McPin Foundation, sessions were attended by psychiatrists, dieticians, occupational therapists, policymakers, managers, commissioners, pharmacists and service users. Findings from RESOLVE served as a foundation for discussions, and healthcare professionals from the UK and international mental health services (including learning disabilities, forensic psychiatry, and early intervention in psychosis) shared experiences and discussed how they may implement change in local settings.

Results: Thematic analysis of workshop transcripts and notes revealed key challenges and opportunities in developing an effective preventative pathway. Stakeholders highlighted several areas for improvement:

Holistic approaches – current interventions are often fragmented, lacking integration across services.

Shared Responsibility – The need for collaborative care among different HCPs and services was emphasised.

Improved access to information – service users and professionals expressed the importance of psycho-education and clear, accessible resources to facilitate proactive management.

As a direct result of this work, multiple healthcare organisations are implementing and evaluating preventative weight management pathways tailored to their local needs and available resources. These quality improvement (QI) projects mark a significant step toward embedding sustainable change in routine care.

Conclusion: This work has emphasised the need for a novel preventative pathway to mitigate the risks of antipsychotic weight gain. Future research will work alongside these organisations to examine real-world implementation, identifying facilitators and barriers to integrating preventative pathways into everyday clinical practice. By doing so, this initiative aims to bridge the gap between physical and mental healthcare, improving long-term health outcomes for individuals living with SMI.

Aims: This systematic review sought to compare the effect of assisted dying options on self-determination, patients’ quality of life, and specific/ethical concerns including suicidality for adults with severe psychiatric disorders and psychiatric or palliative care.

Methods: The data sources gathered for this review were PubMed, EMBASE, CINAHL and Cochrane databases. The search terms consisted of different forms of assisted dying to which various forms of psychiatric and mental health-related terms were added. The papers were restricted to systematic reviews and meta-analyses as these give high-quality evidence. Out of 343 studies after strict criteria such as ROBINS 1, ROB2 and AMSTAR, only 3 studies qualified for the review. The review centred on adults with severe psychiatric disorders, specifically patients with eating disorders who had assisted dying between 2012 and 2024.

Results: The present review estimated that at least 60 individuals with eating disorders who received assisted dying between 2012 and 2024 were reported across 10 peer-reviewed studies and 20 government reports. Clinical rationales for granting assisted dying requests fall into three main domains: non-treatability, prognosis and request of the patient. Most of the reports highlighted two aspects: that the patients had a terminal or untreatable disease, as well as sufficient decision-making abilities. Still, only a few reports were available for the government and many of them failed to provide adequate data on psychiatric conditions.

The review showed that there were significant gaps in reporting assisted deaths for psychiatric patients and ministers questioned accountability and patient safety. Some clinical justifications were void of rigour or evidence indicating the plausibility of the irremediability or lack of decisional capacity in psychiatric relatedness.

Conclusion: The findings of this systematic review can be concluded as indicating the lack of procedural clarity and strengthened precaution measures for assisted dying in the field of psychiatry. The results imply the applicability of the ethical principles as well as clinical considerations call for incremental case-by-case analyses. The study should be extended to propose improved reporting systems for assisted dying and to confirm clinical justification for several patients who received help in psychiatric practices, with the consideration of patient rights and safety.

Aims: Postnatal Depression (PND) is the most prevalent mental health disorder during the postpartum period. Evidence suggests that clinical practice guidelines (CPGs) have the potential to improve the mental well-being of these women. A systematic review of the CPGs for PND, addressing both pharmacological and non-pharmacological recommendations, is currently lacking in the literature. We aim to identify the existing CPGs for the management of PND and to collect the specific recommendations reported by them.

Methods: We conducted this review following the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive search was performed in 5 electronic databases (Medline, Embase, PsycINFO, TRIP, and Epistemonikos) and guideline-specific websites (GIN, NICE, SIGN, and WHO) to identify the currently available English language CPGs for the management of PND, published between 2012 and 2023. General characteristics of the CPGs, as well as reported pharmacological and non-pharmacological recommendations, were extracted. The AGREE-II instrument was used to assess the methodological quality of CPGs based on a cut-off point of 70% and above.

Results: The search strategy identified 1096 records of which 71 were assessed for full text. We identified 19 CPGs: with only one from a lower-middle-income country (Lebanon). All CPGs recommended cognitive-behavioural Therapy (CBT) as the preferred psychological therapy based on level 1 evidence (Systematic review and meta-analysis). Pharmacological interventions were included by 17 CPGs with Selective Serotonin Reuptake Inhibitors (SSRIs) being the most recommended medication based on level 2 evidence (Randomized control trial). Nine CPGs used the “GRADE Criteria” for the determination of the strength of the recommendations. Only three CPGs incorporated Patient and Public Involvement and Engagement in the form of an advisory group. Six CPGs matched the criteria of adequate quality by achieving an overall score of ≥70%.

Conclusion: This review highlights the lack of evidence-based CPGs in lower-middle-income countries (LMICs), which have the largest burden of disease. The application of CPGs from higher-income countries in LMICs is challenging due to significant cultural differences and the availability of evidence from their own settings. CBT and SSRIs were the most common pharmacological and non-pharmacological interventions reported in these CPGs.

Aims: Historically, healthcare professionals were prone to experiencing turmoil of emotions prominent to psychological trauma due to the nature of their work. The healthcare professionals were subjected to elevated risks of psychological elements, leading to mental health implications due to the aftermath of the COVID-19 pandemic. By extension, these mental health repercussions can highly affect the patients’ care as they profoundly affect the healthcare professionals from offering the best quality of care. Different types of digitalised psychological interventions exist and seem to be making an increased trend into being added into the medical field. They are becoming increasingly popular for mental health improvements due to their cost-effectiveness, their scalability, their ability to offer greater anonymity and stigma reduction compared with traditional interventions. Randomised controlled studies (RCTs) were systematically reviewed to explore the effectiveness of digital interventions which are available for healthcare professionals who experience psychological trauma.

Methods: A comprehensive search was conducted across four electronic databases, Pubmed, Medline Ovid, Embase Ovid, PsychINFO Ovid, resulting in a total of six RCTs that met inclusion criteria. Assessment of study quality and risk of bias were conducted using the Jadad scale and Cochrane Risk of Bias Tool respectively. Whilst the RCTs included in the review investigated the efficacy of interventions on healthcare professionals’ wellbeing, the modalities of the interventions varied. Interventions included smartphone-based stress management modules, resilience training, smartphone applications focusing on emotional skills, cognitive-behavioural therapy exercises and psychoeducation, as well as computerised Eye Movement Desensitisation and Reprocessing (EMDR) intervention and internet intervention enhancing self-efficacy. As a result, a meta-analysis was not applicable to be carried out.

Results: Based on the findings, digital interventions had positive impacts on reducing the mental strain experienced by healthcare professionals. Some studies proved that the improvements were of statistical significance. The results of the RCTs in this review looked promising for the future of digital interventions targeting the mental wellbeing of healthcare professionals. In particular, the computerised EMDR intervention and the self-guided internet intervention targeting self-efficacy or social support, illustrated the potential benefits in its results. However, other studies indicated the need for further research before definitive conclusions can be drawn. The majority of the studies used a smartphone-based intervention. However, there was no correlation between the efficacy of these RCTs and this feature of their modality.

Conclusion: The scarce literature available in relation to this topic displayed promising evidence that digital interventions helped healthcare professionals experiencing psychological trauma.

Aims: To explore the physical health of YP admitted to adolescent inpatient mental health units and reflect on any differences over the following 6 months.

Research Questions: 1. To assess physical health of young people upon admission to adolescent inpatient services (cardiovascular risk factors e.g. BMI, blood pressure, blood glucose and lipids). 2. To assess current lifestyle behaviours of young people upon admission to adolescent inpatient wards (e.g. physical activity, diet, smoking rates). 3. To assess changes in physical health/lifestyle 3 months and 6 months post-admission. 4. To understand the impact of inpatient care environment on lifestyle behaviours and physical health of adolescents admitted to inpatient units. 5. To understand the experiences and beliefs about physical health in adolescents admitted to inpatient units. 6. To establish the feasibility of monitoring physical health in a cohort of young people upon admission to an adolescent inpatient unit.

Methods: We aimed to recruit young people aged 14+ from each participating site within 6 weeks of admission to the unit. The young person needed to be able to give informed consent and be well enough to take part (severe anorexia/eating disorder excluded). Physical and mental health assessments were completed by a researcher in conjunction with the clinical team. Assessments completed at three time points: Baseline on admission; 3 months post admission; 6 months post admission. Participants given £10 voucher at each timepoint as a thank you (total £30).

Measures collected included: Demographic information, e.g. age, gender, ethnicity, education, diagnoses, previous admissions, medication, length of admission; Physical Health Outcomes, e.g. BMI (centiles), BP, routinely collected blood tests (random glucose, lipids, etc), ECG; Behavioural Outcomes, e.g. physical activity levels, smoking status, diet, physical fitness (six-minute walk & questionnaire), substance use, comorbid physical health disorders and concurrent treatments; Mental Health Outcomes, e.g. Health of the Nation Outcome Scales for Children and Adolescents (HONOSCA), World Health Organization Wellbeing Index (WHO-WI).

Results: Physical health outcome (Weight): Baseline – 64.5. 3 months – 67.7. 6 months – 69.3. Behavioural outcome: Low levels of physical activity (average 20 mins sport and 1 hour walking per day); High levels of sedentary behaviour; Most common substances used were alcohol (n=11, 44%), tobacco (n=10, 40%) and cannabis (n=6, 25%); Most YP self-reported average fitness levels; Consumed on average 1.8 meals per day (ranged from 1–5).

HONOSCA outcome: 80% lack of concentration (68% severe); 75% self-harmed; 56% difficulties with relationships at home (30% severe); 88% anxious or low mood (44% severe); 64% impairments with educational ability; 64% stopped attending education.

Qualitative interviews (thematic analysis): Outcomes on Young peoples knowledge, Autonomy, environment, sources of support, independence and facilitators.

Conclusion: Young people on CAMHS inpatient units have multiple factors affecting their physical health; Already showing some signs of compromised physical health, likely to worsen; Observed lots of challenges with transitory care and barriers to following people up after discharge; Future work will focus on breaking down some of the barriers experienced to living well; Working on refining a physical health intervention.

Aims: The relationship between depression and dementia represents a complex clinical phenomenon that continues to challenge our understanding of neurodegenerative disease progression. This review synthesizes the most recent evidence examining whether depression serves as a risk factor, prodromal marker, or common confounding comorbidity in dementia development.

Methods: A comprehensive review of recent research studies analysing the psychiatric markers associated with dementia onset were reviewed to develop a clinical framework for understanding and analysing the degree to which these psychiatric phenotypes are representing either risk factors, prodromal psychiatric markers or simply overlapping psychiatric comorbidity.

Results: Recent longitudinal research has revealed that mental disorders, particularly depression, significantly increase dementia risk, with symptoms manifesting up to two decades before dementia diagnosis. This research demonstrated that depressive symptoms often emerge as early as 15 years before formal dementia diagnosis, suggesting its potential role as a prodromal marker. These findings align with recent meta-analytic evidence confirming depression as an independent risk factor for dementia development.

Research has identified specific inflammatory pathways linking depression and neurodegeneration, with elevated inflammatory markers serving as a potential biological bridge between these conditions. This neuroinflammatory process appears to be bidirectional, with depression potentially increasing inflammatory markers that may accelerate cognitive decline, while neurodegenerative processes can trigger inflammatory responses that exacerbate depressive symptoms. These biological markers suggest shared pathophysiological pathways between depression and neurodegenerative processes, with inflammation playing a central role in both conditions.

Conclusion: The synthesis of research findings has significant implications for understanding and developing appropriate clinical practice and preventive strategies. The identification of depression as a risk factor, confounding variable and potential prodromal marker, is generally supported by robust longitudinal evidence and biological mechanisms and emphasizes the need for early intervention and regular monitoring of cognitive function in individuals with late-life depression. The evidence suggests a complex multifactorial interplay where depression may serve as a risk factor, comorbidity and an early manifestation of neurodegenerative processes, highlighting the importance of comprehensive assessment and long-term monitoring of depressed elderly patients for cognitive decline.

Aims: Preparation for the MRCPsych CASC exam can present unique challenges for psychiatry trainees, including limited access to structured practice, real-time feedback and standardized patient interactions. This project aimed to develop the MRCPsych CASC Simulator (MCS), a custom AI-powered tool designed to enhance exam preparation by providing interactive clinical simulations, structured feedback and objective performance assessment.

Methods: The simulator incorporated three core roles – Doctor (candidate), Patient (actor), and Examiner – to create realistic CASC exam stations. MCS was trained in the functional aspects of the CASC, the requirements of both doctor and patient roles, along with the psychiatric expertise, knowledge and resources required. To test performance, we utilized validated assessment tools, including the examiner’s marking sheet for the CASC, Simulated Patient Rating Scale (SPRS), Objective Structured Clinical Examination (OSCE) the Communication Assessment Tool (CAT) to ensure objective and standardized evaluation. The simulator was tested in two roles, doctor and patient, by two different human assessors. The interactions were recorded and replayed for each assessment. Five stations were completed for each role from various psychiatric specialties. These scores were used to compare MCS with stock ChatGPT and to gain an overall understanding of MCS’ performance. Additionally, assessors requested MCS for immediate feedback on their questioning style, response phrasing, diagnostic accuracy and communication skills to gauge MCS’ effectiveness in providing feedback.

Results: The assessors found that MCS was competent in psychiatric assessments and patient simulation. MCS provided comprehensive learning support including mnemonics, diagnostic frameworks and summaries which facilitated differential diagnosis, clinical reasoning and memorisation. MCS provided real-time performance tracking, allowing potential candidates to refine their skills through iterative practice and targeted improvements.

MCS proved to be a significantly more effective tool for CASC practice than stock ChatGPT, scoring higher in both doctor and patient roles. MCS outperformed stock ChatGPT by an average 58% in doctor roles and 25% better in patient roles. Overall, the assessors found MCS to be a vital tool in CASC preparation.

Conclusion: MCS offers a novel and effective approach to psychiatric exam training by providing structured, objective and interactive practice opportunities. Its ability to provide tutoring, simulate realistic patient interactions and offer personalized feedback enhances clinical reasoning, communication skills and exam preparation.

Aims: Emerging evidence suggests that disruptions in brain energy metabolism – including impaired insulin signalling, altered glucose utilization, and mitochondrial dysfunction – may contribute to psychiatric and neurodevelopmental disorders such as bipolar disorder, schizophrenia, depression, post-traumatic stress disorder (PTSD), and autism spectrum disorder (ASD).

Ketogenic metabolic therapies (KMTs) provide the brain with an alternative energy source in the form of ketone bodies, which have been hypothesized to restore metabolic balance and improve psychiatric symptoms. Here we review the potential therapeutic effects of KD for mental health.

Methods: A structured review of recent clinical research was conducted to evaluate the influence of KMT on psychiatric and neurodevelopmental disorders. Relevant studies were identified through a manual selection process.

Results: Across studies, KMTs were associated with improvements in both psychiatric and metabolic outcomes. Patients with severe mental illness – like schizophrenia and bipolar disorder – demonstrated symptom reduction, decreased psychotropic medication use, and, in some cases, remission. Individuals with metabolic impairments experienced resolution of metabolic syndrome criteria alongside psychiatric symptom improvements. Case series also indicate that KMTs may support symptom remission in depression and anxiety. Early clinical research and preliminary findings indicate the feasibility and potential benefits of KMTs in PTSD and ASD. Most studies monitored adherence to KMT through ketone testing, recognizing adherence as a key factor in achieving therapeutic outcomes.

Conclusion: These findings highlight the potential of KMTs as adjunctive treatments in psychiatry. Symptom improvements across mood disorders, PTSD, and ASD, along with metabolic benefits, warrant further clinical investigation. Metabolic psychiatry presents a novel approach to understanding and treating these conditions by targeting brain energy metabolism.

Aims: ‘Flow’ is a transcranial direct current stimulation (tDCS) treatment for depression that patients use at home. Meta-analyses of randomised sham-controlled trials (RCTs) show tDCS is safe, easy to use, and associated with significant improvements in depressive symptoms and high rates of clinical response and remission relative to placebo sham stimulation. Flow is BSI and CE-marked for treating depression in the UK, with NICE guidance for use in the NHS.

Flow incorporates an evidence backed healthy lifestyle behaviour training software app, and depression symptom tracking that enables users and their clinicians to monitor progress/symptoms. Training modules on: ‘Behaviour activation’, ‘Mindfulness’, ‘Exercise for your brain’, ‘An anti-depression diet’, and ‘Therapeutic sleep’.

In a first for the NHS, Northamptonshire Healthcare NHS Foundation Trust’s (NHFT) Specialist Perinatal Mental Health and Maternal Loss Psychology Service offered Flow to their patients with a diagnosis of depression and evaluated the feasibility and impact.

Methods: The patient self-administers Flow tDCS treatment, sessions last for 30 minutes, and are repeated 5 times weekly for 3 weeks, and after the initial 3-week period, patients self-administer 3 sessions per week for 3 weeks, and then as long as required. Outcome measure data collection from baseline to 6-week follow-up point. Self-report measures used were depression: Personal Health Questionnaire (PHQ-9); health related quality of life: EQ-5D-5L; and real-world functioning: Work and Social Adjustment Scale (WSAS). In-depth interviews were undertaken with 14 patients.

Results: There has been high level of adherence in the 25 participants to treatment protocol. There has been statistically significant improvements in depression symptoms (large effect size), real-world meaningful functioning, and health-related quality of life. Reliable improvement and remission rates for PHQ-9 were 64% and 52% respectively. In in-depth interviews most participants described a positive impact on depressive symptoms, sleep, social life, and functioning.

Conclusion: Flow has been successfully integrated into Perinatal Mental Health and Maternal Loss Psychology Service depression treatment offer. It is important to offer NHS patients an evidence-backed alternative to existing depression treatments (antidepressant medication and talking therapies), many patients stop antidepressants when they become pregnant, and many do not tolerate antidepressants side effects or wish to try due to side effects and withdrawal issues. Findings provide support for the approach of delivering both tDCS and on-line wellbeing behaviour therapy training to patients with experience of depression.

Aims: Drug-related deaths are a tragedy, with socioeconomic deprivation associated with higher rates. Globally deaths have increased with most involving an opioid. We aimed to assess the rates and causes of drug-related deaths for a deprived city in Northern England, compared with the surrounding less deprived semirural county (with pockets of high deprivation) against national data. We want to assess whether there is an association of deaths with higher deprivation levels.

Methods: Drug-related deaths in 2022 were provided by Dr Copeland via the National Programme of Substance Use Mortality (NPSUM) using postmortem (PM) records. Two deaths did not have full postcodes, so not included where location was required. We assessed deaths against demographics, implicated drugs, prescribed medications, comparing with Indices of Multiple Deprivation (IMD) by postcode. Regional deaths were compared with Office for National Statistics (ONS) death rates. Statistical analysis via Excel.

Results: In 2022, there were 91 deaths for the city and county (14.8/100,000) significantly higher than (8.14/100,000) in England and Wales (X²=16.4, p<0.00001). The city had significantly more deaths (N=67;25.0/100,000, X²=95.6, p<0.00001) versus the county (N=18;5.2/100,000). Mean age of death 43.2±9.0 and 23% were women. Most deaths in the county occurred in urban areas. Median age of death for Males was 42.6 yrs. and Females 45.2 yrs. (SD±9.0). Most implicated drug causing death was heroin and morphine (23.1%), methadone (16.5%) like national data, whilst benzodiazepines (15.4%) were higher than national (p>0.05). Most deaths were caused by more than one implicated drug 82.4%. 64.8% of deaths occurred in a person known to be using drugs. Many deaths had methadone implicated (N=28; 30.8%) and 50 deaths had methadone at PM of which 11 were prescribed. Most deaths (N=55; 64.7%) occurred in the top decile of IMD and occurred in the top 4.4% most deprived neighbourhoods.

Conclusion: Socioeconomic deprivation was associated with higher rates of drug-related deaths; most deaths occurred in the most deprived areas. Addressing deprivation-related risks in economically challenged areas is critical to effectively tackling drug deaths and health inequalities. The cause of death was most often opioids and strategies such as take-home naloxone and optimising opioid substitution treatment will be vital to reduce deaths. We note a high proportion of deaths had methadone, which was not prescribed, present at postmortem, indicating that prescribed methadone may have been diverted. Drug services may consider strategies to increase use of supervised consumption as per guidelines to reduce diversion and associated deaths.

Aims: Cholinergic dysfunction is key in dementia with Lewy bodies (DLB), and likely to influence the cognitive and psychiatric symptoms of this condition. However, patterns of spatial covariance in DLB in terms of nicotinic acetylcholine receptors (nAChRs) is unknown. In this study we used 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (1235IA-85380) SPECT (α4β2 nAChR assessment) to investigate the covariance patterns in DLB and their associations with cognition.

Methods: Fifteen DLB and 16 healthy controls underwent 1235IA-85380 and rCBF (99mTc-exametazime) SPECT scanning. We applied voxel principal components (PC) analysis, generating a series of PC images representing common intercorrelated voxels across subjects. Linear regression generated specific α4β2 nicotinic and rCBF covariance patterns that contrasted DLB from controls.

Results: A α4β2 pattern that distinguished patients from controls (F1,29 = 165.1, p<0.001), showed relative decreased uptake in bilateral temporal pole, inferior frontal, amygdala, olfactory cortex, insula, anterior/mid cingulate and putamen, as well as relative preserved/increased uptake in sensorimotor, fusiform and occipital lobe, implicating regions in a nicotinic receptor expression sense, within limbic, salience, default mode, olfactory, sensorimotor and visual networks. We then successfully derived from patients, α4β2 nicotinic receptor patterns that correlated with CAMCOGtotal (r=−0.52, p=0.04), MMSE (r=−0.68, p=0.01) and CAMCOGmemory (r=−0.70, p=0.01), demonstrating a common ‘cognitive’ topography of relative decreased binding in lateral/medial prefrontal, lateral temporal, inferior parietal and thalamus along with relative preserved/increased binding in cingulate, insula, occipital and medial temporal regions, structures representing a range of networks supporting executive, language, social cognition, attention and sensory functions.

Conclusion: In conclusion, disease and cognitive related patterns of cholinergic α4β2 nicotinic receptor binding were apparent in DLB and could inform future therapeutic targets of these receptors in this condition.

Aims: Clozapine, the first and most effective atypical antipsychotic for schizophrenia, is typically reserved for treatment-resistant cases due to its serious adverse effects. Recent studies have linked clozapine to an increased risk of haematological malignancies (HM). This meta-analysis is the first to systematically investigate this association.

Methods: We performed this study in accordance with the Cochrane Handbook for Systematic Reviews and Meta-analysis of Interventions. Eligible studies included involving patients treated with clozapine, regardless of the primary psychiatric diagnosis, cohort, case-control, cross-sectional that reported the association between clozapine use and the risk of haematological malignancies.

Results: Five studies were included in our meta-analysis (three retrospective cohorts and two case-control studies) involving a total of 211,427 patients. The overall odds of developing HM were significantly higher in the clozapine group compared with the control group (OR=2.1, 95% CI, 1.39–3.18, p=0.00005, I2=83%). Sensitivity analysis was conducted, and heterogeneity was resolved by exclusion of the study by Brainerd et al. The overall effect after its exclusion suggested a significant increase in the odds of HM (OR=2.45, 95% CI, 1.75–3.43, p< 0.00001, I²=48%). Subgroup analysis showed that the odds of developing leukaemia (OR=4.02, 95% CI, 2.22–7.27, p<0.00001), and lymphoma (OR=6.27, 95% CI, 2.83–13.9, p<0.00001) were significantly higher than the combined risk for all HM. There was no significant association between clozapine and HM with a cumulative dose of <999 defined daily doses (DDD) (OR=1.11, 95% CI, 0.85–1.46, p=0.44) or 1000–2999 DDD (OR=1.34, 95% CI, 0.76–2.34, p=0.31). However, for patients with a cumulative dose of 3000–4999 DDD and >5000 DDD, the risk of HM was significantly higher in the clozapine group (OR=2.04, 95% CI, 1.46–2.86, p<0.0001), (OR=2.45, 95% CI, 1.32–4.48, p=0.004), respectively. The association between clozapine and haematological malignancies became statistically significant after 5 years of follow-up (OR=2.32, 95% CI, 1.5–3.59, p=0.0002).

Conclusion: Despite the increased risk of HM, clozapine treatment in schizophrenia patients is associated with a significantly lower long-term all-cause mortality rate compared with other antipsychotic use. The small risk should not deter its use or not fuel “clozapine-phobia”. The clinical implication of our study is to raise awareness among the psychiatrists about this risk. Haematological abnormalities could be interpreted as typical adverse effects of clozapine, leading to diagnostic bias and delays in malignancy diagnosis.

Aims: It has been shown that 5-hydroxytryptamine3 (5-HT3) receptors are involved in the pathogenesis of schizophrenia. This systematic review and meta-analysis of randomized clinical trials (RCTs) evaluates the efficacy and safety of ondansetron, a potent 5-HT3 receptor antagonist, as adjunctive treatment for the management of schizophrenia, especially the negative symptoms and cognitive deficits.

Methods: A comprehensive search of electronic databases, including PubMed, Scopus, Cochrane, and Web of Science, was performed in October 2024. We included only randomized controlled trials (RCTs), and their data were extracted and analysed using RevMan 5.4 software. The primary outcome was the PANSS (Positive and Negative Syndrome Scale) negative subscale.

Results: Eight RCTs involving 533 patients were included in the study. Ondansetron showed a statistically significant improvement in PANSS negative subscale at 12 weeks [pooled as mean difference, MD=−2.96, 95% CI [−4.69, −1.24], p=0.00007] and in general psychopathology scale [MD= −2.71, 95% CI [−3.52, −1.90]] compared with placebo. However, ondansetron and placebo did not differ in reduction of PANSS positive subscale [MD= 0.1, 95% CI [−1.19, 1.38], p=0.88], and depression scale (SMD= 0.71, 95% [−0.35, 1.77], p=0.19). Ondansetron showed no significant difference regarding tardive dyskinesia between the two groups. However, constipation was significant in the ondansetron group over placebo.

Conclusion: The study’s findings support the use of ondansetron as adjuvant therapy in the management of schizophrenia, particularly the negative symptoms and cognitive deficits.

Aims: Major depressive disorder (MDD) may be linked to broader pathophysiological pathways such as oxidative stress, inflammation, vascular dysfunction, and neuroplasticity alterations. Pentoxifylline (PTX), a pleiotropic drug, targets all these pathways through non-specific phosphodiesterase (PDE) inhibition. This is the first systematic review and meta-analysis to examine the role of PTX in major depressive disorder.

Methods: A comprehensive search of electronic databases, including PubMed, Scopus, Cochrane, and Web of Science, was performed in October 2024. We included only randomized controlled trials (RCTs), and their data were extracted and analysed using Reman 5.4 software. The inclusion criteria as follows: adult patients diagnosed with MDD were included as the population. The intervention considered was pentoxifylline, either alone or in combination with selective serotonin reuptake inhibitors. Comparators included placebo, either alone or combined with SSRIs. Eligible studies needed to report outcomes such as the Hamilton Depression Rating Scale (HAM-D).

Results: Four RCTs with 318 patients were included in the study. PTX showed a statistically significant improvement in HAM-D scores at the primary endpoint compared with the placebo (MD=−3.84, 95% CI [−4.87 to −2.81], p<0.00001). Moreover, PTX showed a statistically significant increase in serotonin and BDNF levels (MD=20.76 ng/mL, 95% CI [5.49 to 36.04], p=0.008; and MD=10.83 ng/mL, 95% CI [−0.22 to 21.88], p=0.05, respectively) and a statistically significant decrease in TNF-α and IL-6 levels (MD=−3.24 pg./mL, 95% CI [−4.12 to −2.36], p<0.00001; and MD=−2.64 pig/mL, 95% CI [−3.79 to −1.48], p<0.00001, respectively). There was no statistically significant difference between the PTX and placebo in any of the reported side effects including nausea, vomiting, headache, diarrhoea, increased appetite, and sexual dysfunction.

Conclusion: The study findings suggest that PTX may be effective and safe as an adjuvant antidepressant agent in patients with MDD, demonstrating a significant reduction in HAM-D scores. The results of this study need to be interpreted with caution considering several limitations.

Aims: It is estimated that the prevalence of obsessive-compulsive disorder (OCD) in the UK is 2–3%, with a lifetime prevalence of anxiety and/or depression being reportedly much higher (estimated at 20–25%). Prevalence rates within medical students have, however, been reported by numerous studies and systematic reviews to exceed those identified in the general population. The primary aim of the current pilot study was to investigate the efficacy of an Acceptance and Commitment Therapy (ACT)-based online intervention in reducing symptom severity within a sample of medical students screened for OCD, anxiety and depressive traits and symptoms. The hypothesis was that the ACT-based online intervention would reduce symptom severity in participants.

Methods: Participants were recruited from Cardiff University’s School of Medicine and were required to complete baseline screening measures for OCD, anxiety, and depressive traits using the Obsessive-Compulsive Inventory-Revised version (OCI-R), the State Trait Anxiety Inventory (STAI), and the Beck Depression Inventory-Revised version (BDI-II), respectively. A total of 11 medical students were recruited following screening and completed two parts of an online ACT-based intervention over a two-week period. Participants were required to complete the same measures post-intervention and were debriefed following their participation. Ethical approval for this study was provided by the university’s School of Medicine Research Ethics Committee.

Results: Data collated was analysed to measure for any differences pre and post intervention. A reduction in OCD symptom severity was reported, however with findings approaching significance (z=−1.362, p>0.05). A significant difference in pre and post intervention scores was not revealed for depressive traits, however a significant reduction in anxiety was revealed using the STAI measure pre and post intervention, (z=−2.59, p<0.01).

Conclusion: The findings of the current pilot highlight the efficacy of our ACT-based online intervention in significantly reducing anxiety in a cohort of medical students. Whilst a small sample was recruited for this pilot, the results warrant further investigation and consideration by university student services in adopting the intervention for students.

Aims: Withania somnifera widely known as “Ashwagandha”, is a key treatment herb in the Indian system of medicine that has been used for thousands of years. It has anti-inflammatory, neuroprotective, adaptogenic, and immunomodulatory activities.

Methods: From inception through September 8, 2024, we searched for randomized clinical trials investigating the effect of ashwagandha on adults. The literature search involved PubMed, Web of Science, Scopus, and Cochrane databases. We included all randomized controlled trials that met the following criteria: (1) conducted on adult participants with stress and/or anxiety; (2) investigated the effects of ashwagandha supplementation compared with a placebo or other active treatments; (3) reported outcomes using validated measures of stress and anxiety. Two reviewers independently extracted the relevant data from the included studies using an Excel sheet. The analysis was carried out using R (version 4.4.1) and the metafor package (version 4.6.0).

Results: A total of 15 studies were included with a combined sample size of 873 patients. We found that ashwagandha supplementation significantly reduced anxiety compared with placebo according to the Hamilton Anxiety Rating Scale (HAM-A) before μ =−1.55 (95% CI: −2.45 to −0.65, p=0.0007) and at 8 weeks of treatment μ=−3.52 (95% CI: −6.00 to −1.04, p=0.0053). It has also showed a signifacnt effect in reducing both stress (Perceived Stress Scale (PSS) μ=−4.88 (95% CI: −7.84 to −1.91, p=0.0013)) and cortisol levels μ=−2.3626 (95% CI: −3.2622 to −1.4629), p<0.0001) at 8 weeks of treatment. On the other hand, no improvement in the quality of life has been observed μ =−1.7618 (95% CI: −5.6118 to 2.0881, p=0.3698).

Conclusion: Ashwagandha supplementation is safe and effective in reducing stress and anxiety in adult patients. In our study, it resulted in a statistically significant reduction of cortisol levels, PSS scale, and HAM-A scale. However, it showed no statistically significant improvement in the quality of life of participants receiving it.

Aims: Sex and gender are critical determinants in the diagnosis, progression, and management of psychiatric conditions, influencing disease epidemiology, symptom presentation, treatment responses, and access to care. However, the extent to which these factors are systematically incorporated into UK psychiatric clinical guidelines has been unclear. To date, no review has assessed how sex and gender considerations are addressed in guidelines produced by the National Institute for Health and Care Excellence (NICE) or the Scottish Intercollegiate Guidelines Network (SIGN).

This study aimed to evaluate the extent of sex and gender integration within psychiatric guidelines. It is the first to systematically assess these dimensions across NICE’s “Mental health, behavioural, and neurodevelopmental conditions” category and SIGN’s “Mental health and behavioural conditions” category, which encompass psychiatric and related conditions.

Methods: A systematic review of all NICE and SIGN psychiatry guidelines was conducted to assess how sex and gender considerations were incorporated across key areas: epidemiology, clinical presentation, investigations, and management. The gender composition of guideline committee chairs was also evaluated. Psychiatry guidelines were ranked relative to other medical specialties to determine their comparative performance.

Results: This review identified significant gaps in the integration of sex and gender considerations across NICE and SIGN psychiatry guidelines. Across NICE psychiatry guidelines, only 72% referenced sex and/or gender, and just 28% addressed these factors beyond reproductive contexts. While differential disease management (52%) and epidemiology (28%) were the most frequently considered aspects, investigations (17%) and clinical presentation (7%) were rarely discussed.

Psychiatry ranked second among NICE specialty categories for integrating sex and gender considerations, and scored second-best for women committee chair representation. This is significant because guidelines chaired by women tended to incorporate sex and gender considerations more comprehensively than those chaired by men. Results from SIGN psychiatry guidelines demonstrated similar trends.

Thematic analysis revealed that NICE and SIGN psychiatry guidelines were more likely than other specialties to acknowledge gendered challenges in accessing care, caregiving roles, social support networks, and current evidence gaps.

Conclusion: As a specialty in which both biological and social determinants are central to diagnosis and treatment, psychiatry is well-positioned to lead improvements in sex and gender-sensitive clinical guidance. Despite psychiatry’s relatively strong performance compared with other specialties, significant gaps remain, particularly in differentiated clinical presentations. NICE and SIGN must establish robust mechanisms to embed sex and gender disaggregated evidence into guidelines. Psychiatrists have a critical opportunity to drive improvements to enhance equity and patient outcomes.

Aims: It is estimated that 1 in 100 individuals in the UK population are on the autistic spectrum. There is known to be a marked gender difference, with a male to female ratio of about 3:1. Previously, this diagnostic discrepancy was attributed to autism spectrum disorder (ASD) being known as a “male-dominant” condition, but in recent years this concept has been disproven and the prevalence of ASD in females is thought to be similar to that of males. This literature review aims to explore current research investigating the gender differences in the clinical presentation of ASD, and how this may contribute to the challenges many girls and women experience in receiving a timely diagnosis.

Methods: Three databases (PubMed, Scopus, and Medline) were searched for studies on the gender differences in the presentation of ASD in children and adolescents. In the screening process, an exclusion criterion was applied to the records according to relevance to the research question. The studies identified were then assessed for eligibility against a final inclusion criterion, resulting in six studies being included in the final review.

Results: Results showed that girls with ASD typically received a diagnosis at an older age than their male counterparts. Girls were also more likely to receive an alternative diagnosis to ASD, often mental health-related, before being given an ASD diagnosis. Repeated and Restricted Behaviours and Interests (RRBIs), which are considered as characteristic and often diagnostic features in ASD, were more prevalent in boys in early childhood. Girls with ASD often had to present with more severe deficits in intellectual ability (IQ), social and communicative skills, or speech and language skills, to be diagnosed with ASD in comparison with their male counterparts.

Conclusion: The studies included in this literature review demonstrated that, whilst in some cases differences in clinical presentation of ASD in boys and in girls may be mild, there are undoubtedly differences present. This is not surprising considering the heterogeneity of ASD as a spectrum disorder. Research investigating the various phenotypes of ASD is hugely beneficial in widening the perception from the traditional concept of ASD being viewed as a “male disorder”. There is a clear need for more research to be done to close the gender gap in the diagnosis of ASD and facilitate more timely diagnosis in girls and women and appropriate interventions at an earlier stage, thereby improving quality of life.

Aims: Schizophrenia affects approximately 20 million people worldwide, with 30% of cases being classified as treatment resistant schizophrenia (TRS) cases. Clozapine remains the gold standard for managing TRS, but around 40% of patients treated with clozapine fail to demonstrate optimal treatment response. This literature review aims to evaluate various augmentation strategies used to enhance clozapine’s effectiveness for TRS, assessing data from systematic reviews and meta-analyses published between 2010 and 2024, the aim of which is to identify whether there is a consensus surrounding augmentation strategies used, whilst simultaneously assessing the quality of the existing research, and recommending where further research could guide future clinical practice and prescribing in TRS.

Methods: A systematic search was conducted in February 2024 across Ovid and PubMed databases using the keywords “schizophrenia”, “clozapine”, and “augmentation”. Inclusion criteria were: studies focusing on clozapine augmentation with another pharmacological agent, systematic reviews or meta-analyses published between 2010 and 2024, and studies from credible peer-reviewed sources. Case reports, single-agent studies, and non-peer-reviewed sources were excluded. A total of 181 papers were screened and, after applying inclusion and exclusion criteria, three systematic reviews were selected for analysis. The quality of each study was assessed using the CASP checklist.

Results: Grover et al. (2022) concluded that augmentation with antipsychotics (specifically aripiprazole) and Electroconvulsive Therapy (ECT) provided the most promising results. Siskind et al. (2018) supported the use of aripiprazole, fluoxetine, sodium valproate, and memantine for overall psychosis symptoms, while memantine was highlighted for its use in negative symptoms of schizophrenia. Porcelli et al. (2011) emphasised that several strategies showed promise, but methodological limitations prevented firm recommendations being made. Aripiprazole and ECT were highlighted, but only tentatively given the sample sizes and potential biases. Across all reviews, aripiprazole was identified as an effective pharmacological augmentation agent option, with ECT also emerging as a beneficial adjunct. However, many trials were repeated across the reviews, which may introduce bias and skew conclusions, limiting their relevance within the broader treatment realms.

Conclusion: This review establishes a need for more rigorous longitudinal studies to determine the most effective augmentation strategies for clozapine in TRS patients. The evidence remains inconclusive due to methodological issues like small sample sizes and study heterogeneity. Future research should prioritise comparative efficacy trials, long-term follow-ups, and increased participant diversity – especially addressing under-representation of women in schizophrenia research. These efforts are essential to improving treatment outcomes for TRS patients who remain symptomatic despite being on clozapine.

Aims: Major depressive disorder (MDD) and treatment-resistant depression (TRD) are significant public health challenges that not only severely affect quality of life but also place a substantial burden on healthcare systems. Individuals with TRD are at an increased risk of suicide, making early intervention essential.

Two prominent neuromodulation treatments, electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS), are commonly used in clinical practice. Despite numerous studies comparing these interventions, definitive conclusions regarding their relative efficacy in treating depression are still lacking. This systematic review aims to compare the antidepressive effects of ECT and TMS, as measured by the Hamilton Depression Rating Scale (HAM-D), whilst also evaluating their clinical feasibility, tolerability, and patient acceptability to guide evidence-based treatment decisions.

Methods: A systematic literature review was conducted using the PubMed and Scopus databases, using keywords “TMS AND depression”, “ECT AND depression”, and “TMS OR ECT AND depression”. Out of 170 initially retrieved articles, six studies met the inclusion criteria of directly comparing the effects of ECT and TMS in patients diagnosed with MDD or TRD. Three other studies were also included in the analysis for their valuable insights on related outcomes.

Results: The findings suggest that ECT has a superior short-term antidepressive effect compared with TMS. Specifically, ECT achieved a response rate of 64.4% and remission rate of 53%, whereas high frequency rTMS (HFrTMS) yielded response and remission rates of 48.7% and 32.2%, respectively. Low frequency rTMS (LFrTMS) demonstrated a notably lower response rate of 20%. In cases of psychotic depression, ECT led to a 58.8% reduction in HAM-D scores, whilst TMS produced a 38% reduction. However, bilateral rTMS (BL-rTMS) emerged as a promising option, offering moderate efficacy alongside superior tolerability and lower dropout rates.

Conclusion: Whilst ECT remains the most effective short-term treatment for depression, its need for general anaesthesia and seizure induction may limit its acceptability. Despite being considered safe and effective by many psychiatrists, the stigma surrounding ECT creates a potential barrier to its widespread acceptance. TMS, particularly BL-rTMS, presents a less invasive alternative with better tolerability, making it a potentially reasonable option for patients and clinicians. These findings highlight the importance of personalised treatment plans that consider clinical severity, patient preference, and available resources. Future longitudinal studies are needed to assess long-term outcomes and adverse effects, such as the mild memory loss associated with ECT in the long term, to further refine the role of these neuromodulation therapies in managing MDD and TRD.