Using Electronic Health Records to Facilitate Precision Psychiatry.

The use of clinical prediction models to produce individualized risk estimates can facilitate the implementation of precision psychiatry. As a source of data from large, clinically representative patient samples, electronic health records (EHRs) provide a platform to develop and validate clinical prediction models, as well as potentially implement them in routine clinical care. The current review describes promising use cases for the application of precision psychiatry to EHR data and considers their performance in terms of discrimination (ability to separate individuals with and without the outcome) and calibration (extent to which predicted risk estimates correspond to observed outcomes), as well as their potential clinical utility (weighing benefits and costs associated with the model compared to different approaches across different assumptions of the number needed to test). We review 4 externally validated clinical prediction models designed to predict psychosis onset, psychotic relapse, cardiometabolic morbidity, and suicide risk. We then discuss the prospects for clinically implementing these models and the potential added value of integrating data from evidence syntheses, standardized psychometric assessments, and biological data into EHRs. Clinical prediction models can utilize routinely collected EHR data in an innovative way, representing a unique opportunity to inform real-world clinical decision making. Combining data from other sources (e.g., meta-analyses) or enhancing EHR data with information from research studies (clinical and biomarker data) may enhance our abilities to improve the performance of clinical prediction models.

Pediatric traumatic brain injury as a risk factor for psychosis and psychotic symptoms: a systematic review and meta-analysis.

BACKGROUND: Psychosis is one of the most disabling psychiatric disorders. Pediatric traumatic brain injury (pTBI) has been cited as a developmental risk factor for psychosis, however this association has never been assessed meta-analytically. METHODS: A systematic review and meta-analysis of the association between pTBI and subsequent psychotic disorders/symptoms was performed. The study was pre-registered (CRD42022360772) adopting a random-effects model to estimate meta-analytic odds ratio (OR) and 95% confidence interval (CI) using the Paule-Mandel estimator. Subgroup (study location, study design, psychotic disorder v. subthreshold symptoms, assessment type, and adult v. adolescent onset) and meta-regression (quality of evidence) analyses were also performed. The robustness of findings was assessed through sensitivity analyses. The meta-analysis is available online as a computational notebook with an open dataset. RESULTS: We identified 10 relevant studies and eight were included in the meta-analysis. Based on a pooled sample size of 479686, the pooled OR for the association between pTBI and psychosis outcomes was 1.80 (95% CI 1.11-2.95). There were no subgroup effects and no outliers. Both psychotic disorder and subthreshold symptoms were associated with pTBI. The overall association remained robust after removal of low-quality studies, however the OR reduced to 1.43 (95% CI 1.04-1.98). A leave-one-out sensitivity analysis showed the association was robust to removal of all but one study which changed the estimate to marginally non-significant. CONCLUSIONS: We report cautious meta-analytic evidence for a positive association between pTBI and future psychosis. New evidence will be key in determining long-term reliability of this finding.

The association between visual hallucinations and secondary psychosis: a systematic review and meta-analysis.

INTRODUCTION: Visual hallucinations are often considered to be suggestive of a secondary cause of psychosis, however, this association has never been assessed meta-analytically. We aimed to compare the presence of visual hallucinations in patients with psychosis due to a primary or secondary cause. METHOD: We conducted a meta-analysis of case-control studies directly comparing primary and secondary psychosis. A random-effects model, following the DerSimonian and Laird method, was used to pool studies and generate overall odds ratios (OR), 95% confidence intervals (CI) and prediction intervals (PI). RESULTS: Fourteen studies (904 primary and 804 secondary psychosis patients) were included. Visual hallucinations were significantly associated with secondary psychosis (OR = 3.0, 95% CI = 1.7-5.1, p < 0.001) with moderate between-study heterogeneity (I2 = 70%). Subgroup analysis by type of secondary psychosis (organic, drug-induced, mixed) was non-significant. Analysis of the content of visual hallucinations (51 primary and 142 secondary psychosis patients) found hallucinations of inanimate objects were significantly more likely to be associated with secondary psychosis (OR = 0.1, 95% CI = 0.01-0.8, p = 0.03). CONCLUSIONS: Visual hallucinations were strongly associated with a secondary cause of psychosis. The presence of visual hallucinations in a patient presenting with psychosis may serve as a potential "red flag" for a secondary cause and warrant further investigation.

Early neutrophil trajectory following clozapine may predict clozapine response - Results from an observational study using electronic health records.

BACKGROUND: Clozapine has unique effectiveness in treatment-resistant schizophrenia and is known to cause immunological side-effects. A transient spike in neutrophils commonly occurs in the first weeks of clozapine therapy. There is contradictory evidence in the literature as to whether neutrophil changes with clozapine are linked to treatment response. AIMS: The current study aims to further examine the neutrophil changes in response to clozapine and explore any association between neutrophil trajectory and treatment response. METHODS: A retrospective cohort study of patients undergoing their first treatment with clozapine and continuing for at least 2 years identified 425 patients (69% male/31% female). Neutrophil counts at baseline, 3 weeks and 1 month were obtained predominantly by linkage with data from the clozapine monitoring service. Clinical Global Impression- Severity (CGI-S) was rated from case notes at the time of clozapine initiation and at 2 years. Latent class growth analysis (LCGA) was performed to define distinct trajectories of neutrophil changes during the first month of treatment. Logistic regression was then conducted to investigate for association between the trajectory of neutrophil count changes in month 1 and clinical response at 2 years as well as between baseline neutrophil count and response. RESULTS: Of the original cohort, 397 (93%) patients had useable neutrophil data during the first 6 weeks of clozapine treatment. LCGA revealed significant differences in neutrophil trajectories with a three-class model being the most parsimonious. The classes had similar trajectory profiles but differed primarily on overall neutrophil count: with low, high-normal and high neutrophil classes, comprising 52%, 40% and 8% of the sample respectively. Membership of the high-normal group was associated with significantly increased odds of a positive response to clozapine, as compared to the low neutrophil group [Odds ratio (OR) = 2.10, p-value = 0.002; 95% confidence interval (95% CI) = 1.31-3.36]. Baseline neutrophil count was a predictor of response to clozapine at 2 years, with counts of ≥5 × 109/l significantly associated with positive response (OR = 1.60, p-value = 0.03; 95% CI = 1.03-2.49). CONCLUSIONS: Our data are consistent with the hypothesis that patients with low-level inflammation, reflected in a high-normal neutrophil count, are more likely to respond to clozapine, raising the possibility that clozapine exerts its superior efficacy via immune mechanisms.

Prevalence of Neuroradiological Abnormalities in First-Episode Psychosis: A Systematic Review and Meta-analysis.

Importance: Individuals presenting with first-episode psychosis (FEP) may have a secondary ("organic") etiology to their symptoms that can be identified using neuroimaging. Because failure to detect such cases at an early stage can have serious clinical consequences, it has been suggested that brain magnetic resonance imaging (MRI) should be mandatory for all patients presenting with FEP. However, this remains a controversial issue, partly because the prevalence of clinically relevant MRI abnormalities in this group is unclear. Objective: To derive a meta-analytic estimate of the prevalence of clinically relevant neuroradiological abnormalities in FEP. Data Sources: Electronic databases Ovid, MEDLINE, PubMed, Embase, PsychINFO, and Global Health were searched up to July 2021. References and citations of included articles and review articles were also searched. Study Selection: Magnetic resonance imaging studies of patients with FEP were included if they reported the frequency of intracranial radiological abnormalities. Data Extraction and Synthesis: Independent extraction was undertaken by 3 researchers and a random-effects meta-analysis of pooled proportions was calculated. Moderators were tested using subgroup and meta-regression analyses. Heterogeneity was evaluated using the I2 index. The robustness of results was evaluated using sensitivity analyses. Publication bias was assessed using funnel plots and Egger tests. Main Outcomes and Measures: Proportion of patients with a clinically relevant radiological abnormality (defined as a change in clinical management or diagnosis); number of patients needed to scan to detect 1 such abnormality (number needed to assess [NNA]). Results: Twelve independent studies (13 samples) comprising 1613 patients with FEP were included. Of these patients, 26.4% (95% CI, 16.3%-37.9%; NNA of 4) had an intracranial radiological abnormality, and 5.9% (95% CI, 3.2%-9.0%) had a clinically relevant abnormality, yielding an NNA of 18. There were high degrees of heterogeneity among the studies for these outcomes, 95% to 73%, respectively. The most common type of clinically relevant finding was white matter abnormalities, with a prevalence of 0.9% (95% CI, 0%-2.8%), followed by cysts, with a prevalence of 0.5% (95% CI, 0%-1.4%). Conclusions and Relevance: This systematic review and meta-analysis found that 5.9% of patients presenting with a first episode of psychosis had a clinically relevant finding on MRI. Because the consequences of not detecting these abnormalities can be serious, these findings support the use of MRI as part of the initial clinical assessment of all patients with FEP.

What are the barriers and facilitators of clozapine use in early psychosis? A survey of UK early intervention clinicians.

Clozapine is the most effective medication for treatment-resistant psychosis, but evidence points to substantial underuse, especially within early intervention psychosis (EIP) services. We explored clinicians' views on perceived barriers and facilitators to offering patients clozapine within EIP services. A cross-sectional survey was distributed electronically to clinicians practising in EIP services across England. A mixed methods approach was used to assess barriers to clozapine, and attitudes and opinions concerning clozapine underutilisation. Based on the barriers identified in the literature, clinicians were asked to rate each one (scale:1-7) based on importance, with a higher score indicating higher importance. Clinicians were also asked open-ended questions on barriers to clozapine and how access can be improved in EIP services. Quantitative data were analysed using descriptive and inferential statistics, and qualitative responses were analysed thematically. One hundred and nineteen EIP clinicians from 35 services in England completed the survey. In total, 37% (n = 45) of clinicians perceived that clozapine was under-prescribed in their EIP service. The most important barrier to utilising clozapine were patient concerns with side effects, followed by monitoring requirements and clinician concerns with side effects. Thematic analysis identified 17 perceived barriers, which were grouped into three major themes: administrative (5 subthemes), clinician-related (6 subthemes), and patient-related (6 subthemes). Perceived facilitators to improving clozapine use were greater training, improved resources, and optimised monitoring. The main barriers to clozapine in EIP services, as identified by clinicians, are patient concerns regarding side effects and monitoring requirements. Identified facilitators for improved clozapine use include clinician training, improved resources, guidelines, and point-of-care testing.

Serum immune markers and transition to psychosis in individuals at clinical high risk.

Individuals at clinical high risk (CHR) for psychosis have been found to have altered cytokine levels, but whether these changes are related to clinical outcomes remains unclear. We addressed this issue by measuring serum levels of 20 immune markers in 325 participants (n = 269 CHR, n = 56 healthy controls) using multiplex immunoassays, and then followed up the CHR sample to determine their clinical outcomes. Among 269 CHR individuals, 50 (18.6 %) developed psychosis by two years. Univariate and machine learning techniques were used to compare levels of inflammatory markers in CHR subjects and healthy controls, and in CHR subjects who had (CHR-t), or had not (CHR-nt) transitioned to psychosis. An ANCOVA identified significant group differences (CHR-t, CHR-nt and controls) and post-hoc tests indicated that VEGF levels and the IL-10/IL-6 ratio were significantly higher in CHR-t than CHR-nt, after adjusting for multiple comparisons. Using a penalised logistic regression classifier, CHR participants were distinguished from controls with an area-under the curve (AUC) of 0.82, with IL-6 and IL-4 levels the most important discriminating features. Transition to psychosis was predicted with an AUC of 0.57, with higher VEGF level and IL-10/IL-6 ratio the most important discriminating features. These data suggest that alterations in the levels of peripheral immune markers are associated with the subsequent onset of psychosis. The association with increased VEGF levels could reflect altered blood-brain-barrier (BBB) permeability, while the link with an elevated IL-10/IL-6 ratio points to an imbalance between anti- and pro-inflammatory cytokines.

Quantitative EEG as a Prognostic Tool in Suspected Anti-N-Methyl- d -Aspartate Receptor Antibody Encephalitis.

PURPOSE: Anti-N-methyl- d -aspartate receptor (anti-NMDAR) encephalitis is a form of autoimmune encephalitis associated with EEG abnormalities. In view of the potentially severe outcomes, there is a need to develop prognostic tools to inform clinical management. The authors explored whether quantitative EEG was able to predict outcomes in patients with suspected anti-NMDAR encephalitis. METHODS: A retrospective, observational study was conducted of patients admitted to a tertiary clinical neuroscience center with suspected anti-NMDAR encephalitis. Peak power and peak frequency within delta (<4 Hz), theta (4-8 Hz), alpha (8 - 13 Hz), and beta (13-30 Hz) frequency bands were calculated for the first clinical EEG recording. Outcome was based on the modified Rankin Scale (mRS) score at 1 year after hospital discharge. Binomial logistic regression using backward elimination was performed with peak frequency and power, anti-NMDAR Encephalitis One-Year Functional Status score, age, and interval from symptom onset to EEG entered as predictors. RESULTS: Twenty patients were included (mean age 48.6 years, 70% female), of which 7 (35%) had a poor clinical outcome (mRS 2-6) at 1 year. There was no association between reported EEG abnormalities and outcome. The final logistic regression model was significant (χ 2 (1) = 6.35, P < 0.012) with peak frequency in the delta range (<4 Hz) the only retained predictor. The model explained 38% of the variance (Nagelkerke R2 ) and correctly classified 85% of cases. Higher peak frequency in the delta range was significantly associated ( P = 0.04) with an increased likelihood of poor outcome. CONCLUSIONS: In this exploratory study, it was found that quantitative EEG on routinely collected EEG recordings in patients with suspected anti-NMDAR encephalitis was feasible. A higher peak frequency within the delta range was associated with poorer clinical outcome and may indicate anti-NMDAR-mediated synaptic dysfunction. Quantitative EEG may have clinical utility in predicting outcomes in patients with suspected NMDAR antibody encephalitis, thereby serving as a useful adjunct to qualitative EEG assessment; however, given the small sample size, replication in a larger scale is indicated.

Neuropsychiatric Features of Fregoli Syndrome: An Individual Patient Meta-Analysis.

OBJECTIVE: Fregoli syndrome is a rare delusion characterized by the belief that familiar people are presenting themselves disguised as others to the affected person. Theories of delusional misidentification have suggested secondary ("organic") underlying mechanisms; however, the pathoetiology of Fregoli syndrome has not been systematically evaluated. The investigators aimed to compare the neuropsychiatric features of Fregoli syndrome in primary and secondary psychoses. METHODS: A systematic review and patient-level meta-analysis were conducted. Five databases were searched, ultimately yielding 83 studies that met selection criteria. Demographic characteristics, diagnosis, delusional content, neuropsychiatric features, investigations, and treatment information were extracted. Random-effects models were calculated, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: A total of 119 patients with Fregoli syndrome were identified: 62 patients (52%) with primary psychosis, 50 (42%) with secondary psychosis, and seven (6%) with an unclear etiology. Patients with secondary psychosis were less likely than patients with primary psychosis to experience persecutory features (OR=0.26, 95% CI=0.10, 0.67; p=0.0057). Moreover, patients with secondary psychosis were more likely to experience Fregoli syndrome during a first episode of psychosis (OR=11.00, 95% CI=2.45, 49.39; p=0.0017). Right-sided brain lesions were more prominent than left-sided brain lesions in the total sample (χ2=5.0, df=1, p=0.025) and in the secondary psychosis subgroup (χ2=4.26, df=1, p=0.039). CONCLUSIONS: This is the first meta-analysis to investigate Fregoli syndrome. An estimated 42% of the reported cases involved a secondary etiology. These findings provide clinicians with a better understanding of the symptomatology of Fregoli syndrome and have potential to be applied in future research and clinical practice.

Clozapine haematological monitoring for neutropenia: a global perspective.

AIMS: Clozapine is licensed for treatment-resistant psychosis and remains underutilised. This may berelated to the stringent haematological monitoring requirements that are mandatory in most countries. We aimed to compare guidelines internationally and develop a novel Stringency Index. We hypothesised that the most stringent countries would have increased healthcare costs and reduced prescription rates. METHOD: We conducted a literature review and survey of guidelines internationally. Guideline identification involved a literature review and consultation with clinical academics. We focused on the haematological monitoring parameters, frequency and thresholds for discontinuation and rechallenge after suspected clozapine-induced neutropenia. In addition, indicators reflecting monitoring guideline stringency were scored and visualised using a choropleth map. We developed a Stringency Index with an international panel of clozapine experts, through a modified-Delphi-survey. The Stringency Index was compared to health expenditure per-capita and clozapine prescription per 100 000 persons. RESULTS: One hundred twocountries were included, from Europe (n = 35), Asia (n = 24), Africa (n = 20), South America (n = 11), North America (n = 7) and Oceania and Australia (n = 5). Guidelines differed in frequency of haematological monitoring and discontinuation thresholds. Overall, 5% of included countries had explicit guidelines for clozapine-rechallenge and 40% explicitly prohibited clozapine-rechallenge. Furthermore, 7% of included countries had modified discontinuation thresholds for benign ethnic neutropenia. None of the guidelines specified how long haematological monitoring should continue. The most stringent guidelines were in Europe, and the least stringent were in Africa and South America. There was a positive association (r = 0.43, p < 0.001) between a country's Stringency Index and healthcare expenditure per capita. CONCLUSIONS: Recommendations on how haematological function should be monitored in patients treated with clozapine vary considerably between countries. It would be useful to standardise guidelines on haematological monitoring worldwide.

The clinical relevance of serum versus CSF NMDAR autoantibodies associated exclusively with psychiatric features: a systematic review and meta-analysis of individual patient data.

BACKGROUND: A variety of psychiatric syndromes are associated with NMDAR autoantibodies; however, their clinical relevance when only present in the serum is unclear. We explored whether patients with CSF NMDAR autoantibodies could be distinguished from patients with serum-only NMDAR autoantibodies. METHODS: The electronic databases MEDLINE, EMBASE, PubMed, and PsycINFO were searched. Articles reporting adult patients with isolated psychiatric features and positive for NMDAR autoantibodies with relevant investigations were included. Patient level meta-analysis compared patients positive for CSF NMDAR autoantibodies with patients positive for serum NMDAR autoantibodies, but negative for CSF NMDAR autoantibodies. Dichotomous data were analysed using crude odds ratios (OR), whilst continuous data were analysed using Mann-Whitney Test (U). The protocol was prospectively registered (CRD42018082210). RESULTS: Of 4413 publications, 42 were included, reporting 79 patients. Median age was 34 years (IQR 19 years); 56% (45/79) were female and 24% (16/68) had a tumour. In total, 41 patients were positive for CSF autoantibodies and 20 were positive for serum-only autoantibodies. Patients with CSF autoantibodies were significantly more likely to be female (p < 0.001) and have a rapid (< 3 month) onset of symptoms (p = 0.02) than patients with serum-only autoantibodies. They were also more likely to present with psychosis (p < 0.001), exhibit EEG (p = 0.006), MRI (p = 0.002), and CSF (p = 0.001) abnormalities, but less likely to present with insomnia (p = 0.04). CONCLUSIONS: Patients with an isolated psychiatric syndrome with CSF NMDAR autoantibodies can potentially be distinguished from those with serum-only NMDAR autoantibodies based on clinicodemographic and investigation findings.

Clozapine for treatment resistance in early psychosis: a survey of UK clinicians' training, knowledge and confidence.

Background: Clozapine is the only medication licenced for patients with psychosis that is resistant to conventional antipsychotic treatment. However, despite its effectiveness, it remains widely underutilised. One contributory factor for this may be clinicians' lack of confidence around the management of clozapine. Objective: We conducted a survey of clinicians working in Early Intervention in Psychosis (EIP) services to determine their training needs for clozapine management in EIP services. Methods: An electronic survey was made available to all clinicians working in EIP services in England. The survey assessed confidence and training needs regarding managing clozapine in patients with treatment-resistant psychosis. Quantitative data were analysed using total mean scores and the Mann-Whitney U test. Results: In all, 192 (27%) of approximately 700 clinicians from 35 EIP services completed the survey. Approximately half (54%) had not received training on treatment with clozapine. Experience of training was higher in prescribers than non-prescribers, and among medical than non-medical clinicians. Previous training was associated with significantly higher confidence in offering clozapine and managing treatment-resistant psychosis (p < 0.001). Confidence levels with managing treatment-resistant psychosis and clozapine were relatively high (mean = 4 out of 5, SD = 1). Respondents were most confident about monitoring mental health response to treatment (mean = 5, SD = 1). Participants were least confident about how to discontinue clozapine treatment safely (mean = 3, SD = 1). Conclusion: Most clinicians working in EIP have not received training on the use of clozapine. This may account, in part, for the underutilisation of clozapine in EIP services. The provision of training in the identification of treatment-resistant psychosis and the use of clozapine will likely improve the detection and management of treatment resistance in the early phase of psychosis.

Reducing the Risk of Withdrawal Symptoms and Relapse Following Clozapine Discontinuation-Is It Feasible to Develop Evidence-Based Guidelines?

Clozapine is the only antipsychotic that is effective in treatment-resistant schizophrenia. However, in certain clinical situations, such as the emergence of serious adverse effects, it is necessary to discontinue clozapine. Stopping clozapine treatment poses a particular challenge due to the risk of psychotic relapse, as well as the development of withdrawal symptoms. Despite these challenges for the clinician, there is currently no formal guidance on how to safely to discontinue clozapine. We assessed the feasibility of developing evidence-based recommendations for (1) minimizing the risk of withdrawal symptoms, (2) managing withdrawal phenomena, and (3) commencing alternatives treatment when clozapine is discontinued. We then evaluated the recommendations against the Appraisal of Guidelines for Research and Evaluation (AGREE) II criteria. We produced 19 recommendations. The majority of these recommendation were evidence-based, although the strength of some recommendations was limited by a reliance of studies of medium to low quality. We discuss next steps in the refinement and validation of an evidence-based guideline for stopping clozapine and identify key outstanding questions.

Clozapine discontinuation withdrawal symptoms in schizophrenia.

Clozapine is an atypical antipsychotic used in treatment-resistant schizophrenia. Whilst clozapine is highly effective, there are some clinical scenarios, such as the emergence of severe side effects, that necessitate its discontinuation. There is an emerging literature suggesting that discontinuing antipsychotics, in particular clozapine, can cause an array of withdrawal symptoms. We review the evidence for the existence of clozapine-induced withdrawal symptoms, and in particular focus on withdrawal-associated psychosis, cholinergic rebound, catatonia and serotonergic discontinuation symptoms. To date, there has been surprisingly little clinical guidance on how to minimise the likeliness of withdrawal symptoms in patients who are stopped on clozapine abruptly or gradually. We discuss the key outstanding questions in this area and why there is a need for guidance on the management of withdrawal symptoms associated with clozapine discontinuation.

Clozapine Response in Schizophrenia and Hematological Changes.

BACKGROUND: Clozapine is the only effective medication for treatment-resistant schizophrenia; however, its mechanism of action remains unclear. The present study explored whether its effectiveness is related to changes in hematological measures after clozapine initiation. METHODS: Patients with treatment-resistant schizophrenia commenced on clozapine between January 2007 and December 2014 by the United Kingdom's largest mental health trust were identified from electronic patient records. Hematological data from these patients were obtained from a monitoring registry. White blood cell, neutrophil, and platelet count were assessed at baseline and during the early phase of clozapine treatment. Clozapine response at 3 months was defined as "much," or "very much" improved on the seven-point Clinical Global Impression-Improvement (CGI-I) subscale. RESULTS: In the total sample (n = 188), clozapine initiation was associated with a significant transient increase (peaking in weeks 3 to 4) in white blood cell, neutrophil, and platelet count (P < 0.001). There were 112 (59.6%) patients that responded to treatment; however, none of the hematological factors assessed at baseline, nor changes in these factors, were directly associated with treatment response. IMPLICATIONS: Clozapine treatment is associated with transient hematological changes during the first month of treatment; however, there was no evidence that these were related to the therapeutic response.

Focussing on the fundaments - assessing and treating Clozapine Induced Gastrointestinal Hypomotility.

Background: Clozapine is a second-generation antipsychotic used in treatment-resistant Schizophrenia (TRS). Clozapine Induced Gastrointestinal Hypomotility (CIGH) is the commonest cause of clozapine related death, yet remains under-recognised and under-monitored.Aims and hypothesis: To review the pharmacological management of CIGH. We hypothesised that pharmacological interventions would reduce the incidence of adverse outcomes associated with CIGH.Methods: We retrospectively reviewed consecutive patients treated on clozapine over a one year period on a male acute psychiatric ward. Information on patient demographics, CIGH symptomatology, treatment and outcome were extracted.Results: In total, 14 male patients with a mean age of 43 years (standard deviation 10 years) were included. Of these, 9 patients experienced CIGH during admission, in all cases presenting as constipation. Among patients experiencing CIGH, 8 of 9 (89%) patients received one or more interventions. This was most commonly a stimulant, or osmotic laxative. By discharge, the 8 patients treated were in full remission of CIGH symptoms.Conclusions: A high proportion of patients treated with clozapine experience CIGH, presenting most commonly as constipation. Whilst potentially life-threatening, CIGH can be successfully treated in an acute inpatient setting. Active monitoring of CIGH symptoms in patients initiated, or reinitiated on clozapine is recommended.Key pointsA high proportion of patients treated with Clozapine experience constipation, the cardinal feature of Clozapine Induced Gastrointestinal Hypomotility.Whilst potentially life-threatening, CIGH can be successfully treated in an acute inpatient setting with simple interventions.Active monitoring of CIGH symptoms in patients initiated, or reinitiated on clozapine is recommended.Future research on the potential benefit of prophylactic intervention would be beneficial.

Transient Musical Hallucinations in a Young Adult Male Associated with Alcohol Withdrawal.

We present the case of a 25-year-old male who presented to A&E with isolated musical hallucinations, in the absence of audiological or neurological disease. The patient had a history of recreational drug use and a family history of psychosis. Hallucinations, which were preceded by discontinuation of alcohol and reinitiation of citalopram for depression, resolved spontaneously after three days. Aetiological factors are discussed alongside the existing literature. Whilst the underlying mechanisms underpinning musical hallucinations remain elusive, the case illustrates the potential role of alcohol withdrawal, serotonin toxicity, recreational drug use, and genetic vulnerability.

Catatonia and the immune system: a review.

Catatonia is a psychomotor disorder featuring stupor, posturing, and echophenomena. This Series paper examines the evidence for immune dysregulation in catatonia. Activation of the innate immune system is associated with mutism, withdrawal, and psychomotor retardation, which constitute the neurovegetative features of catatonia. Evidence is sparse and conflicting for acute-phase activation in catatonia, and whether this feature is secondary to immobility is unclear. Various viral, bacterial, and parasitic infections have been associated with catatonia, but it is primarily linked to CNS infections. The most common cause of autoimmune catatonia is N-methyl-D-aspartate receptor (NMDAR) encephalitis, which can account for the full spectrum of catatonic features. Autoimmunity appears to cause catatonia less by systemic inflammation than by the downstream effects of specific actions on extracellular antigens. The specific association with NMDAR encephalitis supports a hypothesis of glutamatergic hypofunction in catatonia.