Methylphenidate is a relatively safe medication used frequently in ADHD with only a few dermatological side effects reported up-to-date. While direct relation between the medication and the dermatologic side effects on children are discussed and supported by the disappearance of reactions after medication withdrawal, other confounding factors such as parental stress and coping mechanisms, were indeed observed to have a direct impact on children’s wellbeing. The higher the maternal anxiety was related to the worse outcome in children with stress. This fact could explain recently emerged or prolonged skin reactions especially during the pandemic, as it provokes health-related anxiety, especially in vulnerable people.

Our case is a 9-year-old boy with ADHD who experienced digital desquamation after using methylphenidate-containing prescriptions. To the best of our knowledge, he was the first child having persistent non-pruritic, non-painful acral swelling and desquamation without any benefit from discontinuation of medications containing methylphenidate, and without any rheumatological condition.

There have been a few unusual adverse skin reactions to Methylphenidate reported, differing widely from general to local, pruritic to non-pruritic, and exfoliative to non-exfoliative. Our case had local non-pruritic exfoliation started 2 months after initiation of Methylphenidate -IR, however, the symptoms did not disappear after the withdrawal of prescriptions.

Persistent peeling after discontinuation of any Methylphenidate prescription was a unique situation. Thus, we investigated whether Methylphenidate has triggered and/or masked any rheumatologic condition especially juvenile rheumatoid arthritis and juvenile scleroderma. He was examined by a paediatrician with no anomaly found. Another reason for such prolonged skin reaction could be personal and parental stress. This could also explain why he has abdominal pain triggered only by going to school, as it may be related to parental expectations in addition to his ADHD and dyslexia comorbidity. The literature findings support the idea that high maternal anxiety elicits worse health outcomes in children with a neurodevelopmental disorder. Unfortunately, we could not have a chance to assess the anxiety level and coping mechanisms of the mother of our case, other than observing her stress-related behaviours as frequent doctor visits, to have a more concrete debate.

Any skin finding after methylphenidate prescription must be monitored closely to have early preventive measures, better adherence to treatment, and quality of life for both patients and their parents. Also, both children and their parents could be controlled for stress and coping mechanisms to diminish their negative effects on dermatological or any other health-related outcome.

Achalasia is a rare oesophageal motility disorder in children and adolescents, presenting with vomiting, regurgitation, dysphagia, weight loss, and anxiety around eating. These features can closely resemble restrictive eating disorders or functional vomiting syndromes, leading to diagnostic uncertainty. Delayed diagnosis is well recognised and may result in severe malnutrition, aspiration, and secondary psychiatric morbidity. We describe an adolescent whose prolonged illness was initially managed within eating disorder pathways before achalasia was identified as the underlying cause.

At 12 years of age, the patient developed eating difficulties in the context of a known anxiety disorder. She reported progressive dysphagia, described as an acidic sensation in the throat and food sticking, alongside regurgitation, reduced appetite, and avoidance of eating at school. Vomiting increased over time, oral intake declined, and significant weight loss ensued.

She was admitted for investigation of possible physical causes. A barium swallow study was attempted but poorly tolerated and completed via nasogastric tube, resulting in inadequate visualisation of the oesophagus. Despite this limitation, the study was reported as normal and no gastroenterology follow up was arranged. Ongoing vomiting and nutritional compromise led to management within eating disorder services and admission to an inpatient eating disorder unit. Atypical anorexia nervosa was the initial working diagnosis.

With structured nutritional rehabilitation, she initially approached weight restoration and was generally engaged in treatment. A previously undisclosed history of self harm emerged, linked to eating related guilt and emotional distress, and fluoxetine was commenced. Although vomiting reduced in frequency, urges persisted and dietary adherence remained inconsistent. She was later diagnosed with ADHD and commenced on methylphenidate.

She subsequently deteriorated, with renewed weight loss, reduced dietary adherence during home leave, and worsening physical symptoms including regurgitation, nocturnal cough, and recurrent chest infections. Symptoms were attributed to reflux and rumination syndrome, and management remained conservative. Progressive nutritional compromise and recurrent infections necessitated nasogastric feeding and detention under the Mental Health Act. Further imaging demonstrated marked oesophageal dilatation with distal narrowing, confirming achalasia. She underwent laparoscopic Heller myotomy, after which regurgitation, vomiting, and chronic cough resolved. Postoperatively, she achieved sustained weight restoration and tolerated oral intake without dysphagia.

This case highlights how achalasia can closely mimic eating disorder presentations when early investigations are inconclusive. In adolescents with persistent dysphagia, regurgitation, vomiting, and weight loss refractory to eating disorder treatment, early reconsideration of gastrointestinal pathology may prevent prolonged psychiatric admissions and significant medical morbidity.

Drug resistant first episode psychosis in a 17-year-old adolescent male with autism spectrum disorder presents with a significant diagnostic and therapeutic challenge especially with associated physical comorbidities. Medication intolerance, persistently low white cell count, partial response and early relapse after discharge remain the prominent risks. This case highlights the complex nature of therapeutic decision making and discharge planning in a high-risk young person.

A 17-year-old adolescent male who was admitted to the in-patient CAMHS unit with a 14-month history of progressive psychotic symptoms characterised by chronic auditory and visual hallucinations, paranoid delusions; alleging his parents to be impostors; depressed mood, anhedonia, and social withdrawal. With a diagnosis of autism spectrum disorder, history of significant trauma, years of school bullying and street robbery. He has a past medical history of cardiac arrest with unknown aetiology and on treatment with implantable cardioverter defibrillator.

During initial admission, he was polite, compliant with treatment although with partial insight. Family support was robust, and leave was utilized with no significant adverse incidents. Despite participation in ward activities his affect remained predominantly flat with persisting psychotic symptoms albeit with less intensity. Pharmacological management remained challenging, initially commenced on aripiprazole, titrated to 15mg which was discontinued due to significant restless legs symptoms requiring procyclidine. Olanzapine was initiated and gradually increased to a maximum of 12.5 mg with partial stabilization necessitating discharge to the community.

Weeks following discharge, worsening complex delusions and commanding hallucinations and high-risk behaviours in the community was noted. These include fire-setting and possession of weapons.

This led to re-admission and risperidone was trialled and gradually titrated to 5 mg with marked elevation of prolactin with minimal improvement.

Giving treatment resistance, clozapine was considered and is being approached cautiously due to his history of cardiac arrest, persistently low white cell counts and hyperprolactinemia with close psychiatric and cardiology consultation followed with gradual risperidone taper.

This case illustrates the complexity in managing treatment resistant first-episode psychosis in autistic adolescent with significant physical comorbidities.

Careful antipsychotic selection, robust discharge planning, and intensive multidisciplinary follow-up are essential to reduce relapse and serious harm.

The prevalence of attention deficit/hyperactivity disorder (ADHD) diagnoses and stimulant prescribing among women of reproductive age has increased substantially over the past two decades. Dextro-/amphetamine formulations, particularly dexamphetamine, are now among the most commonly used ADHD medications during pregnancy. Clinical decision making is complicated by uncertainty regarding maternal, fetal and long term child outcomes, leading to high rates of medication discontinuation. This review aims to synthesise current evidence on maternal, neonatal, congenital and long term neurodevelopmental outcomes associated with dexamphetamine and related stimulant use during pregnancy.

A narrative review of population based cohort studies, registry analyses and clinical guidelines examining perinatal stimulant exposure was conducted. Outcomes of interest included neonatal and obstetric outcomes, congenital malformations, maternal complications and long term neurodevelopmental outcomes, with careful consideration of confounding by maternal ADHD, behavioural and sociodemographic factors. Studies were selected based on their quality, relevance and inclusion of contemporary perinatal data.

Population level data demonstrate a marked rise in perinatal stimulant use, primarily driven by dexamphetamine, with an 11-fold increase observed in a British Columbia registry study (2000-2021). Retrospective cohort studies suggest that continuing dexamphetamine during pregnancy is generally not associated with adverse maternal or neonatal outcomes compared with cessation. Evidence for hypertensive disorders, however, remains inconclusive. International registry studies report no increased risk of major congenital malformations following amphetamine exposure, with a small signal observed for methylphenidate. Long term follow up studies, after adjusting for confounding by maternal ADHD, found no meaningful increase in neurodevelopmental disorders among children exposed in utero. Maternal ADHD and related behavioural or sociodemographic factors may act as confounders underlining the importance of accounting for these factors in research and clinical decision making.

Current evidence suggests that dexamphetamine exposure during pregnancy is not associated with major increases in adverse maternal, neonatal, congenital or long term neurodevelopmental outcomes when confounding is appropriately addressed. Shared, individualised decision making remains essential. Given the limitations of observational study designs and residual confounding, future research should prioritise dexamphetamine-specific data and include qualitative measures of maternal functioning as well as long term childhood outcomes.

In the light of limited relevant local literature, we planned our research to build a scientific database related to the immediate and sustained effects of this innovative treatment modality at our tertiary care hospital, in order to start ketamine clinic in our department . We didn’t find any research in Faisalabad, Pakistan on the subject, ensuring a more in depth understanding of the tolerability and acceptability of ketamine therapy in our patient population. The research findings will provide an insight into the effective use of ketamine therapy in cases of TRD

It was a non randomized trial held in department of psychiatry DHQ/ Allied Hospitals Faisalabad Medical University, Faisalabad, Pakistan.

Sample size : 30 ( purposive sampling)

The study started after approval from ethical review committee of FMU, Faisalabad. The patients fulfilling inclusion criteria were enrolled and informed consent taken. All patients received detailed informational care session about nature of IV ketamine therapy. IV ketamine was given in subanesthetic dose of 0.5mg/kg body weight in 100ml normal saline infusion over 60 minutes after an overnight fast and under supervision of an anesthetist. Pulse, Blood pressure and oxygen saturation was monitored during infusion to ensure safety . Patient was kept in recovery until fully conscious . 8 Treatment sessions were administered over 4 weeks . Patients were assessed using Hamilton Depression Rating Scale (HAM-D) after each dose, then 2 weeks and finally 1 month after last dose.

A 50% reduction in HAM-D scores at 1 hour after 1st dose was considered as treatment response.

Regarding treatment outcomes, IV Ketamine therapy demonstrated promising results. Out of 30 patients, 22 (73.3%) showed a positive response to ketamine therapy, whereas 8 patients (26.7%) didn’t respond. This finding indicates a relatively high efficacy rate of ketamine in managing TRD within the studied group

This study demonstrates that IV ketamine at a sub anesthetic dose produces rapid and substantial improvement in depressive symptoms among patients with TRD. The response rate of 73.3% is consistent with the global data, reinforcing ketamine’s role as a transformative intervention in modern psychiatric care.The persistence of symptom improvement at two weeks and one month follow up assessments suggests that repeated IV ketamine administration may offer short to medium term benefits in TRD Future researches with larger sample size, longer follow up and controlled designs will be essential to validate these findings and optimize clinical protocols for widespread implementation

Novel psychoactive substances (NPS) present unpredictable pharmacodynamic and pharmacokinetic effects, which can complicate opioid substitution therapy (OST) and increase overdose risk. Understanding patterns of NPS use in OST patients is important for optimizing pharmacological management and harm reduction. This study aimed to identify the prevalence and types of NPS use among OST outpatients, describe associated pharmacological risks, and evaluate whether such use was documented in clinical notes.

A retrospective pharmacological review was conducted in an addictions psychiatry outpatient clinic. Adults aged ≥18 years receiving methadone or buprenorphine were included. Patients were excluded if clinical records were incomplete or if acute intoxication, withdrawal, or cognitive impairment precluded accurate reporting. Data were extracted from patient self-report, toxicology results, and clinical notes, focusing on type of NPS, concurrent substance use, OST dose, and documented adverse events such as sedation, withdrawal, or toxicity. Descriptive analyses summarized prevalence, pharmacological profiles, and documentation.

Among 120 patients (methadone n=75, buprenorphine n=45), 32 patients (27%) reported NPS use, most commonly synthetic cannabinoids (n=16) and cathinone derivatives (n=10). Polysubstance use occurred in 60% of NPS users versus 40% of non-users. Pharmacological complications were reported in 15 NPS users (47%), including enhanced sedation, withdrawal exacerbation, and increased craving. Notably, 23 of 32 patients (72%) had no prior documentation of NPS use in clinical notes, highlighting under-recognition of potential pharmacological risks.

NPS use is common in OST patients and presents significant pharmacological challenges, particularly in the context of polysubstance use. Systematic screening and documentation of NPS exposure is feasible and essential for safe OST management, dose adjustment considerations, and prevention of adverse pharmacological interactions.

Promethazine is a phenothiazine compound first synthesised in the 1940s, with prominent sedative qualities. As a first-generation antihistamine, promethazine has strong affinity as an antagonist of H1histaminergic receptors of the tuberomammillary nucleus, as well as moderate antagonism of muscarinic cholinergic receptors, and weak-moderate affinity to receptors in the serotonergic, dopaminergic, adrenergic and glutaminergic systems. While in the UK promethazine is publicly available ‘over the counter’, it is not recommended by NICE guidelines for insomnia.

We narratively summarise the available evidence for promethazine’s benefit on human sleep outcomes with structured searches, as well as publicly available prescribing trends data from OpenPrescribing and published academic reports.

Promethazine is increasingly prescribed by primary care physicians and psychiatrists in United Kingdom as a treatment for all kinds of sleep concerns, with a near doubling of English GP prescriptions in the past 5 years. There is no good evidence for the clinical benefit of promethazine on sleep outcomes, with an absence of clinical trials or adequate measures of sleep. Use of promethazine as a sleep-aid is actively advised against in international expert consensuses, with evidence based alternatives available including the NICE guidelines’ first-line option, Cognitive-Behavioural Therapy for Insomnia (CBT-I).

For several reasons, it appears that promethazine is not an appropriate treatment for any flavour of sleep problem. First, because there is no clinical trial evidence. Secondly, it is important to remember that sedation is not sleep. These two states of reduced consciousness are different phenomenologically, physiologically, and appear different on EEG recordings. The multiple benefits of natural human sleep cannot be assumed to be achieved by this kind of artificial sedation. Histaminergic antagonism has a very complex pharmacodynamic profile, and psychiatrists cannot expect that there will be linear dose-effects. Third, the addictive nature of promethazine must be acknowledged: there are significant levels of recreational use of promethazine worldwide, in part because of its effects in potentiating opioid agents. Moreover tolerance develops quickly, with diminished sedative effects seen in as few as 3 days. Withdrawal symptoms are common, with rebound insomnia widely reported after long-term use. Finally, the side effect profile of promethazine is of concern including, QTc prolongation, weight gain, and the potent cholinergic effects have a causal effect on dementia. This poster concludes with a summary of alternative approaches for psychiatrists using promethazine in their practice, including CBT-I and alternative, more sleep problem-specific medication options.

Lithium and Valproate remain established mood stabilisers with strong evidence for efficacy in bipolar disorder and affective instability. Contemporary clinical practice increasingly reflects a shift towards alternatives such as lamotrigine and atypical antipsychotics. This shift appears driven not only by clinical considerations but also by regulatory, safety and service-level factors. Valproate prescribing has declined markedly among women of childbearing age due to teratogenic risks and regulatory restrictions, while lithium use is challenged by monitoring requirements and systemic barriers within services. These influences may contribute to the underutilisation of effective treatments, raising concerns about the impact of administrative burden, risk management, and evolving prescribing culture on real-world pharmacological practice.

Aim: This study aimed to examine prescribing patterns of lithium, valproate, and alternative mood stabilisers within an AOT cohort across two time points six months apart. It sought to quantify changes in the use of lithium, valproate, and lamotrigine and to explore whether observed trends reflect broader clinical, regulatory, and service-related influences on prescribing practice.

A retrospective observational review of clinical records was conducted including all patients under the care of the AOT at two defined points, six months apart. Patients prescribed mood stabilisers were identified. Data collected included current mood stabiliser (lithium, valproate, lamotrigine, or other), demographic characteristics (age and sex), clinical indication, and changes in prescribing between time points. Descriptive statistics were used to calculate the proportion of patients receiving each mood stabiliser at both time points. Changes in prescribing patterns over the six-month period were analysed and compared across medication groups to identify emerging trends.

The AOT caseload increased from 73 patients in July 2025 to 85 patients in January 2026. Lithium prescribing decreased slightly from 6 patients (8.2%) to 5 patients (5.9%), while valproate use remained numerically stable at 5 patients (6.8% vs 5.9%). Lamotrigine prescribing increased from 3 patients (4.1%) to 6 patients (7.1%), representing the most notable change over the study period. Carbamazepine use declined from 1 patient (1.4%) to none. Overall, lithium and valproate use remained stable or declined slightly, while lamotrigine use increased despite changes in caseload and patient turnover, indicating a gradual shift in mood stabiliser prescribing patterns within the AOT population.

Findings mirror wider trends in psychiatric prescribing, characterised by a relative decline in lithium use due to monitoring and systemic barriers, regulatory driven constraints on valproate, and increasing reliance on lamotrigine and alternative agents. These results suggest that effective mood stabilisers may be underutilised not because of reduced efficacy but due to evolving regulatory frameworks, risk management priorities, and service-level pressures. Understanding these influences is important for informing prescribing practice and ensuring that clinical decision-making remains balanced between safety, feasibility, and therapeutic effectiveness in complex mental health populations.

Lithium is a first-line mood stabiliser for bipolar disorder but has a narrow therapeutic index. Neuropsychiatric toxicity may occur even when serum lithium concentrations are near the therapeutic range, particularly in the presence of dehydration and acute kidney injury. This case study aims to highlight lithium-associated neuropsychiatric toxicity as an important and potentially overlooked cause of ongoing delirium in patients with bipolar disorder following acute medical illness.

A 74-year-old woman with bipolar disorder treated with long-term lithium therapy was admitted following collapse and acute onset confusion. On presentation, she was febrile, dehydrated, and disoriented, with clinical evidence of cellulitis, leading to an initial diagnosis of acute delirium secondary to sepsis. She was treated empirically with intravenous antibiotics and fluids. Despite improved inflammatory markers, her neuropsychiatric symptoms persisted.

Further investigations revealed mild hypernatraemia, persistent hypercalcaemia, acute kidney injury, and a mildly elevated serum lithium level but her parathyroid hormone levels were within the normal limit. CT and MRI of the brain revealed no acute intracranial pathology. Despite rehydration and resolution of infection, delirium and biochemical abnormalities persisted, prompting review of psychotropic medication.

Lithium toxicity precipitated by dehydration and acute kidney injury was identified as the most likely unifying diagnosis. Lithium dosage was reduced and intravenous bisphosphonate therapy was administered. Following intervention, renal function improved and serum lithium and calcium concentrations normalised. The patient demonstrated gradual and complete resolution of delirium, returning to her cognitive baseline without residual neuropsychiatric impairment at discharge.

This case illustrates that lithium-associated neuropsychiatric toxicity may present with persistent delirium despite near-therapeutic serum levels and apparent alternative medical explanations. Hypercalcaemia and renal impairment served as important diagnostic clues supporting lithium toxicity.

Lithium toxicity should be considered in patients with bipolar disorder who develop persistent delirium, particularly when dehydration and acute kidney injury are present. Near-therapeutic serum lithium levels do not exclude clinically significant neurotoxicity. Early review of psychotropic medication and renal function is essential to prevent delayed diagnosis and avoidable morbidity.

Pregabalin dependence and overuse are a major problem, with individuals often taking doses well above the licensed daily maximum of 600mg. Users frequently combine it with other substances, raising the risk of respiratory depression. The lack of guidance on managing withdrawal from high doses poses a significant challenge in hospital settings. Failure to treat acute withdrawal can lead to severe side effects, including seizures, and may result in patients prematurely discharging themselves.

This abstract reviews the limited guidance on assessing and treating pregabalin withdrawal in hospital settings, proposing a structured, evidence-based approach. Our hypothesis is that this approach can safely mitigate withdrawal symptoms and improve patient outcomes.

The assessment should include evaluating dependence severity and screening for co-existing substance use or mental health disorders. Clinicians should also review clinical notes for previous admissions and, with patient consent, speak with family members for insight into the patient’s drug use. Contacting the local addiction service is important, especially if the patient is on opioid substitute treatment. Point of Care Testing for pregabalin and other drugs can be used, with a positive result supporting a decision to prescribe.

When prescribing pregabalin, the reported dose and objective signs of withdrawal are key. For a reported daily dose of 300-600mg, prescribe 100mg three times daily. For doses over 600mg, an initial dose of 150mg three times daily is recommended, increasing to a maximum of 200mg three times daily if withdrawal persists. Due to common polysubstance use, prescribing diazepam 5mg four times daily is also often required.

Managing high-dose pregabalin withdrawal requires a cautious approach. Patients must be observed for sedation or respiratory depression. Referral to a Mental Health Liaison Service is crucial for advice on tapering and continuity of care. This approach facilitates safer withdrawal and improved outcomes.

Schizophrenia affects 0.43% of global adults, with an estimated annual excess economic burden of $343.2 billion in the United States alone. The schizophrenia drug ecosystem is characterized by significant heterogeneity in patient responses, warranting continual drug discovery efforts to improve outcomes for patients responding suboptimally to existing treatments. Given the centrality of dopamine D2 receptor (DRD2) antagonism in current treatments, this study focused on (i) identifying strong DRD2 binders among Food and Drug Administration (FDA)-approved drugs as repurposing candidates and (ii) generating optimized variants of known antipsychotics as novel drug candidates.

We developed a computational drug discovery pipeline to score potential drug candidates based on DRD2 receptor binding affinity. Molecular docking scores were calculated by dockstring, a Python wrapper for AutoDock Vina, that automatically finds the best binding pose and returns its binding affinity to the receptor. Virtual screening was performed on:

1. ∼1,600 FDA-approved drugs, with emphasis placed on central nervous system-active drugs known to permeate the blood-brain barrier.

2. 450 variant ligands of six reference antipsychotics (haloperidol, trifluoperazine, fluphenazine, chlorpromazine, thioridazine, and risperidone), generated using SwissSimilarity.

A molecular weight threshold of 500 Da was applied to exclude large ligands, consistent with Lipinski’s Rule of 5 for oral bioavailability. Candidates achieving high binding affinity (≤-9.5 kcal/mol) were further evaluated against existing literature.

Among FDA-approved drugs, risperidone achieved the lowest docking score and therefore the best binding affinity (-11.9 kcal/mol), validating our pipeline by recapitulating a known antipsychotic. Several candidates with high predicted binding affinities (≤-9.5 kcal/mol) were identified, with two of particular interest:

• • Dolasetron. Other serotonin 5-HT3 receptor antagonists, especially ondansetron, have improved schizophrenic symptoms in previous studies, making this a promising line of investigation.

• • Trazodone. A population-based cohort study published last year offered evidence that trazodone reduced risk of re-hospitalisation for delirium in older patients as compared to other antipsychotics.

Ligand optimization yielded 4 distinct molecules with superior binding affinities relative to their parent compounds. The best-performing variant achieved -13.6 kcal/mol (risperidone-derived), while the largest improvement was observed for thioridazine (-12.7 kcal/mol versus -8.5 kcal/mol original).

An automated DRD2-focused docking workflow can recover known antipsychotics, surface plausible repurposing candidates, and propose optimized variants with improved predicted binding. While these computational hits require further ADMET analysis and experimental validation before strong conclusions are drawn about clinical potential, our results demonstrate the potential utility of computational drug discovery methods in expanding therapeutic options for schizophrenia.

According to NICE guideline, psychotropic medication has limited role to improve clinical outcome in EUPD patients. However, the practice of utilising psychotropic medication is increasing. The aim of this audit is to assess whether prescribing psychotropic medication in the absence of any other psychiatric co morbidities improves the clinical outcome.

The audit was completed at the Scarisbrick In-patient unit at Lancashire and South Cumbria NHS Foundation Trust. The number of hospital admission within next 1 year of starting psychotropic medication was used as the indicator for clinical outcome. Data was collected retrospectively from the electronic system from the patients’ cohort who were admitted from 01/2023-12/2023, with diagnosis of EUPD in the absence of other psychiatric comorbidities, (N=29) to assess if prescribing psychotropic medication can reduce number of hospital admission within next 1 year (between 01/24- 12/2024).

The result shows high rate of psychotropic medication used in patients with EUPD diagnosis in the absence of any other psychiatric comorbidities. 62% patients were already on antidepressants and 55% on antipsychotics prior to admission. After medication review post admission, 55% started on psychotropics, including 41% on antipsychotics, 35% on antidepressants, and 14% on mood stabilisers.

Despite being on psychotropic medications, the readmission rate within next 1 year remains high. 58.62 % (N=17) patients had re-admissions within one year of starting psychotropics. Of those, 71% (N=12)had more than one admission. 65% (N=11) of readmissions were under the Mental Health Act. For 76% (N=13) patients, admission lasted more than 2 weeks and 24% had crisis admission.

The audit focuses solely on pharmacological data. There is no mention of psychological input, crisis plans, care coordination, which is central to NICE/RCPsych recommendations.

High proportion of patients with EUPD are prescribed psychotropic medications before and during admission, despite the limited evidence supporting their effectiveness in this population. This is not consistent with NICE, which cautions againstroutine psychotropic use in EUPD in the absence of comorbidities or clear indications. Over half of patients were re-admitted to hospital within next one year of starting psychotropic medication and most had multiple re-admissions. The high re-admission rate, particularly under the MHA and with prolonged stays, raises concern about the effectiveness of psychotropic medication in reducing relapse or improving long-term outcomes in EUPD. The data appears to support NICE guidance that psychotropic medications should not be used routinely in the absence of comorbid mental illness, as their benefit in preventing relapse is questionable.

Genetic factors are thought to play an important role in antipsychotic-induced weight gain (AIWG). Polygenic risk scores (PRS) could provide a measure of genetic predisposition to antipsychotic drug induced weight gain (AIWG). We conducted a study to examine how a PRS, generated using SNPs, identified from a recent meta-analysis, related to weight-change over time in people with first episode-psychosis (FEP).

The PRS included SNPs in six different genes, identified as having significant associations (p<0.05) with AIWG. These were HTR2C rs3813929; MTHFR rs1801133; ADRA2A rs1800544; MC4R rs489693; LEPR rs1137101 and CNR1 rs1049353. An additive PRS and a risk allele based weighted PRS were created based on risk allele counts and presence or absence of risk alleles respectively. The additive PRS was also used to create low/high genetic risk groups for analysis. The association between PRS and weight gain per day (WGPD) in grams/day as well as BMI percentage change (=>7%) was investigated using regression models.

In multiple regression analysis, the additive PRS significantly predicted AIWG in females (adjusted r²=0.59, B: unstandardised regression coefficient=24.4 grams/day p <0.05), but not in males. ANCOVA showed that high genetic risk groups had greater WGPD (p=0.018), with significant PRS gender interactions driven by markedly higher WGPD in high-risk females (p=0.039).

Follow-up comparisons indicated that in females, those with ≥7 risk alleles had substantially higher WGPD scores (adjusted Mean=138.8 grams/day, 95% CI [99.6, 178.1]) compared with those with ≤6 alleles (adjusted Mean=40.4 grams/day, 95% CI [−5.5, 86.2]). In males, WGPD scores were not significantly different across genetic risk categories.

We report a PRS that is predictive of weight gain in women treated for first episode psychosis, accounting for 59% of the variance daily weight-gain over time. Validation of the PRS in an independent cohort is required, as is determining whether it is feasible to apply the PRS prospectively in real world clinical settings to inform lifestyle measures and pharmacotherapeutic decisions in the treatment of FEP

‘et al’

Dr Adrian Phillipson, Sheffield Hallam University

Prof. Gavin P. Reynolds, Sheffield Hallam University

Prof. Caroline Dalton, Sheffield Hallam University

In pharmacokinetic studies of xanomeline and trospium chloride (KarXT), dosing with food reduced trospium bioavailability, potentially impacting tolerability. This study was designed to demonstrate taking KarXT with food after a slow up-titration is safe and tolerable.

In pharmacokinetic studies of xanomeline and trospium chloride (KarXT), dosing with food reduced trospium bioavailability, potentially impacting tolerability. This study was designed to demonstrate taking KarXT with food after a slow up-titration is safe and tolerable.

During periods 1 and 2, 64.2% and 39.0% of participants reported ≥1 treatment-emergent adverse event (TEAE), respectively. The most common TEAEs (≥5%) in period 1 were nausea (22.5%), dyspepsia (15.6%), headache (15.0%), constipation (12.7%), and vomiting (11.6%); the incidence of all new onset TEAEs was less in period 2 when taken with food. All TEAEs were mild or moderate in intensity; none were serious. PANSS total score decreased over periods 1 and 2; Clinical Global Impression-Severity score decreased over period 1 with no further change over period 2. Dose-normalized area under the curve and maximum plasma concentration of trospium pooled from cohorts 1 and 2 decreased by 36% and 43%, respectively, when taken with food versus fasting. No clinically significant differences were observed in xanomeline exposure.

After slow uptitration on an empty stomach, there was no increase in the incidence or severity of TEAEs when taking KarXT with food; efficacy was maintained.

Xanomeline/trospium chloride (KarXT) is approved in the US for schizophrenia in adults. KarXT combines the dual M1/M4-preferring muscarinic receptor agonist xanomeline with the peripherally restricted pan muscarinic receptor antagonist trospium chloride to reduce side effects related to xanomeline activation of peripheral muscarinic receptors. KarXT efficacy and safety were demonstrated in the EMERGENT trials and a phase 4 trial evaluating tolerability of administration with/without food. This post-hoc analysis compared onset, duration, and incidence of treatment-emergent adverse events (TEAEs) by KarXT dose (100mg/20mg and 125mg/30mg twice daily [BID]) and titration schedule with data from these completed trials.

The phase 4 “food effect” inpatient, open-label trial (NCT06572449) enrolled adults with schizophrenia, Positive and Negative Symptom Scale (PANSS) total score ≤80, and Clinical Global Impression-Severity (CGI-S) score ≤4. In weeks 1-4, participants began KarXT at 50mg/20mg BID (days 1-7), followed by 100mg/20mg (days 8-14), and increased to a maximum of 125mg/30mg (cohort 1) or continued with 100mg/20mg (cohort 2) (days 15-28). The inpatient, 5-week, randomized, double-blind, placebo-controlled, phase 2EMERGENT-1 (NCT03697252) and phase 3 EMERGENT-2 (NCT04659161) and EMERGENT-3 (NCT04738123) trials enrolled adults with confirmed schizophrenia and recent worsening of psychosis warranting hospitalization, PANSS total score ≥80, and CGI-S score ≥4. KarXT BID dosing began at 50mg/20mg (days 1-2), followed by 100mg/20mg (days 3-7), and increased to a maximum of 125mg/30mg (days 8-35). Food effect trial TEAE analyses by maximum KarXT dose and titration schedule were restricted to weeks 1-4; results from EMERGENT were pooled.

In the food effect trial, KarXT TEAEs occurred in 69.9% (100mg/20mg) and 59.0% (125mg/30mg) of participants; in pooled EMERGENT, rates were 77.8% and 67.1%, respectively. Peak incidence of procholinergic and anticholinergic TEAEs coincided with transition to the KarXT 100mg/20mg dose (food effect: week 2; pooled EMERGENT: days 3-7); incidence of TEAEs plateaued or decreased with transition to KarXT 125mg/30mg. Nausea duration was longer for those maintained on KarXT 100mg/20mg in both datasets. Efficacy was measured by decrease in PANSS total score and observed with 100mg/20mg and 125mg/30mg in both study populations.

Overall, TEAE incidence and duration appeared to be similar regardless of titration speed to KarXT 125mg/30mg BID. Data suggest the duration of certain TEAEs is longer with 100mg/20mg BID, potentially due to the higher ratio of X to T of 5:1 versus 4.1:1. In some circumstances, potential improvements in tolerability may be seen with more rapid titration and/or uptitration to KarXT 125mg/30mg BID.

Clozapine is the only evidence-based medication for treatment-resistant schizophrenia and is associated with reductions in relapse, suicide risk, and all-cause mortality.Nevertheless, its use is restricted by concerns about adverse effects, particularly neutropenia and agranulocytosis, which often result in permanent discontinuation under current UK monitoring rules.

Emerging evidence and regulatory changes, particularly in the United States and Europe, suggest that Clozapine re-challenge may be safe in selected patients following careful individualised risk–benefit assessment. However, Clozapine re-challenge remains uncommon in the UK.

We completed a retrospective case series of patients who underwent Clozapine re-challenge within TEWV NHS Trust.Using CPMS data and clinical records, patients who stopped Clozapine due to neutropenia between 1994 and 2024 were identified. We then checked the data of patients who were re-challenged with Clozapine in detail. Extracted data included demographic characteristics, severity and duration of neutropenic episodes, time to neutropenia following Clozapine initiation, interval between discontinuation and re-challenge, re-challenge strategies (including use of lithium and/or G-CSF) and clinical outcomes.

Successful re-challenge was defined as continued Clozapine treatment without recurrent red blood results requiring permanent discontinuation.

We found that thirteen (46%)out of twenty-eight patientswho discontinued Clozapine due to neutropenia underwent re-challenge.

Eight patients (61.5%) were successfully re-challenged and maintained on Clozapine.

Five re-challenges were unsuccessful and three of which were associated with recurrent severe neutropenia.

No fatalities occurred following Clozapine re-challenge.

Most cases of Clozapine re-challenge were undertaken using Clozapine alone, without adding lithium or G-CSF.

With the exception of two cases, all index neutropenic events occurred beyond the first year of Clozapine treatment, ranging from 17 months to 20 years.

Neither the severity nor the timing of the initial neutropenic episode reliably predicted the rechallenge outcome.

Clozapine re-challenge was successful in a majority of patients, with no deaths observed. Neither severity nor timing of the index neutropenic episode reliably predicted the re-challenge outcome. Therefore,Clozapine re-challenge should be cautiously considered in selected patients, particularly where no effective alternatives exist.

These findings highlight the need for a more flexible and evidence based guidance for Clozapine monitoring and re-challenge.

Clozapine-associated neutropenia occurs in approximately 3.8% of patients globally, with agranulocytosis reported in around 0.9%. Benign ethnic neutropenia (BEN), which is prevalent among Arab and African populations, complicates interpretation of haematological monitoring and may lead to unnecessary treatment interruption. Despite the high representation of BEN-susceptible ethnicities in Gulf populations, regional data on clozapine haematological safety are lacking. This study aimed to estimate the incidence of clozapine-associated neutropenia, identify clinical predictors, and evaluate the role of baseline absolute neutrophil count (ANC) in risk stratification.

A retrospective cohort study was conducted including all patients prescribed clozapine at a tertiary psychiatric hospital in the United Arab Emirates between January 2018 and July 2024. A total of 184 patients were followed over 228.1 patient-years, comprising 3,907 ANC measurements. Neutropenia was defined as ANC <2.0 × 109/L and categorised as mild (1.5–2.0), moderate (1.0–1.5), severe (0.5–1.0), or agranulocytosis (<0.5). Cox proportional hazards regression was used to identify predictors of neutropenia. Receiver operating characteristic (ROC) analysis assessed the discriminatory performance of baseline ANC.

Twenty patients (10.9%; 95% CI 7.1–16.2%) developed neutropenia, corresponding to an incidence rate of 9.74 per 100 patient-years (95% CI 5.95–15.05). Most events were mild (n=19, 10.3%), and no cases of agranulocytosis were observed. Patients of Arab or African ethnicity had significantly higher neutropenia rates compared with other ethnic groups (16.2% vs 1.6%; odds ratio 11.5, 95% CI 1.5–87.5; p=0.001). Baseline ANC emerged as the only independent predictor of neutropenia (hazard ratio 0.15, 95% CI 0.07–0.31; p<0.001), with each unit increase associated with an 85% reduction in risk. Baseline ANC demonstrated excellent discriminatory ability (AUC 0.92, 95% CI 0.86–0.97), with an optimal threshold of 3.3 × 109/L (sensitivity 85%, specificity 87.4%). Clozapine was continued in 80% of affected patients, with no permanent discontinuations due to haematological events.

This first Middle Eastern study of clozapine haematological safety demonstrates neutropenia rates comparable to international data and no observed agranulocytosis. Baseline ANC provides excellent risk stratification, while higher neutropenia rates in Arab and African patients likely reflect benign ethnic neutropenia rather than true drug toxicity. These findings support continued clozapine treatment with appropriate monitoring and highlight the need for ethnicity-informed interpretation of haematological results in diverse populations.

No financial sponsorship was received for this project.

This study aimed to computationally investigate interactions between DAT and a range of ligands across different conformational states using molecular docking and structural modelling, with the goal of identifying residues associated with ligand binding and potential conformational specificity.

Recent Cryo EM structures of DAT representing inward-facing and outward-facing conformations were obtained from the Protein Data Bank and prepared using MODELLER.Eight compounds (Amphetamine, Buproprion, Methamphetamine, Modafinil, Methylphenidate, Mephedrone, Vanoxerine and Nortriptyline) were categorised based on binding preferences. Molecular docking was performed using Cresset Flare, generating ten poses per compound, which were ranked using Lead Finder scores. The lowest-energy protein-ligand interactions were visualised with VMD and further analysed using Schrodinger Maestro and Nanome VR.

In the inward-facing conformation, conserved interacting residues across compounds included Val328, Tyr156, Phe326, and Val152. In the outward-facing conformation, conserved residues included Tyr156, Val152, Ala423, Asp79, Phe320, Phe76, Phe326, Ser149, and Ser422. Asp79 and Val328 were observed to participate in interactions that differed between conformational states.

These results identify recurring residues involved in ligand interactions with DAT and suggest conformation-dependent interaction patterns that may be relevant to transporter modulation. Future work will build on these docked complexes using molecular dynamics simulations with AI-guided analysis of protein dynamics to support drug discovery efforts aimed at the development of novel treatments for stimulant use disorder.

Stimulant use disorder is associated with increasing morbidity, mortality, and high relapse rates, yet there is currently no approved pharmacotherapy. Relapse vulnerability is increasingly recognised as arising from dysregulation across dopaminergic, serotonergic, and noradrenergic neurocircuitry. Serotonin-Norepinephrine-Dopamine Reuptake Inhibitors (SNDRIs) modulate these monoaminergic pathways and represent a mechanism-informed pharmacological strategy. This review aimed to evaluate the neurobiological rationale, translational potential, and emerging clinical feasibility of repurposing SNDRIs for stimulant use disorder.

A review was conducted integrating preclinical neuropharmacological evidence, human neuroimaging and behavioural studies, and clinical trial data examining monoamine transporter modulation. Evidence relating to dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) function was analysed to evaluate reinforcement neurobiology, relapse vulnerability, pharmacokinetic characteristics, and clinical safety data from candidate SNDRIs including dasotraline, centanafadine, and ansofaxine.

Psychostimulant reinforcement is strongly associated with DAT occupancy and dopamine elevation within mesolimbic reward circuitry. However, relapse vulnerability is increasingly linked to serotonergic and noradrenergic dysregulation contributing to stress sensitivity, affective instability, and cue-driven drug seeking. Preclinical evidence demonstrates that NET inhibition reduces stress-induced and cue-mediated stimulant seeking, while SERT modulation influences impulsivity and negative affective states associated with relapse. SNDRIs produce sustained, moderate monoaminergic modulation that normalises hypodopaminergic states observed during stimulant withdrawal without producing rapid dopamine elevations associated with abuse liability. Pharmacokinetic data demonstrates extended elimination half-lives supporting once-daily dosing and improved treatment adherence. Clinical trials investigating SNDRIs in attention-deficit/hyperactivity disorder and major depressive disorder demonstrate favourable tolerability and sustained monoaminergic modulation in human populations. Advances in transporter structural modelling and computational pharmacology support the use of dynamic transporter-ligand profiling to stratify therapeutic development and improve prediction of abuse liability.

SNDRIs demonstrate mechanistic plausibility and clinical feasibility as candidate pharmacotherapies for stimulant use disorder. Multi-transporter modulation may address both reward-driven reinforcement and relapse-related neuropsychiatric processes. However, current evidence remains indirect and derived primarily from mechanistic, preclinical, and non-addiction clinical populations. Targeted, stratified clinical trials in stimulant use disorder populations are required before treatment recommendations can be made.

Anorexia nervosa (AN) is a severe psychiatric disorder with the highest mortality of any mental illness. While psychological therapies such as family therapy remain first-line, up to 30% of adolescents experience partial or non-recovery, prompting interest in adjunctive pharmacological options. Olanzapine, an atypical antipsychotic associated with reduced cognitive rigidity and anxiety and with restorative weight gain, is increasingly used off-label in adolescent AN despite limited evidence and lack of NICE endorsement. This review aimed to synthesise international evidence on olanzapine use in under-18s with AN, evaluating efficacy, safety, tolerability and applicability to UK NHS practice.

A systematic literature search was conducted across multiple bibliographic databases to identify peer-reviewed studies examining olanzapine use in patients under 18 years with anorexia nervosa for the period 2000 – 2025. Eligible study designs included randomised controlled trials (RCTs), open-label and observational studies, case series, audits and clinical guidelines. Findings were synthesised narratively to assess clinical outcomes, adverse effects and implementation within UK Child and Adolescent Mental Health Services (CAMHS).

Thirty-six studies met inclusion criteria. Evidence from adolescent RCTs was limited and underpowered, demonstrating modest effects on weight restoration and variable psychological benefit. In contrast, open-label and naturalistic studies consistently reported short-term improvements in body mass index and reductions in anxiety, rigidity and pre-meal distress, particularly at low doses (2.5 - 5mg/day). Sedation, increased appetite and mild metabolic changes were commonly reported and were generally reversible. A single case of neuroleptic malignant syndrome was identified. Engagement of families in shared decision-making was associated with improved adherence. UK prescribing data indicate ongoing off-label use within specialist CAMHS, reflecting a gap between clinical practice and formal guidance.

Available evidence supports cautious, short-term, low-dose olanzapine use as an adjunct to multidisciplinary care for selected adolescents with treatment-resistant AN, with benefits appearing greatest for psychological symptoms rather than sustained weight restoration. However, the evidence base remains limited by small sample sizes, heterogeneous outcome measures and short follow-up periods. Within UK NHS CAMHS, safe prescribing requires consultant oversight, family consent and metabolic monitoring in line with national standards. Further adequately powered UK-based RCTs are required to clarify efficacy, acceptability and long-term outcomes.