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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.

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.

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 (

Summary 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.

Background: Clozapine is a second-generation antipsychotic used in treatment-resistant Schizophrenia (TRS). Clozapine Induced Gastrointestinal Hypomotility (CIGH) is the commonest cause of clozapin...

We report the first case of a patient with severe, intractable Tourette Syndrome with comorbid Obsessive Compulsive disorder, who recovered from both disorders with gamma-knife (GK) stereotactic radiosurgery following deep brain stimulation (DBS). This case highlights the possible role of the internal capsule within the neural circuitries underlying both TS and OCD, and suggests that in cases of treatment-refractory TS and comorbid OCD, bilateral anterior capsulotomy using stereotactic radiosurgery may be a viable treatment option.

Objectives/AimsFregoli syndrome is a rare delusion characterised by the misidentification of an individual, typically of someone who the patient has an emotional link towards. The pathoaetiology of Fregoli syndrome remains largely a mystery, however, it has been described in patients experiencing either a primary or secondary (organic) psychosis. We sought to compare the neuropsychiatric features of Fregoli syndrome in primary and secondary psychosis.MethodsA patient-level meta-analysis was conducted. Five databases were searched for any descriptions of Fregoli syndrome. The patients and the psychotic episodes details alongside the co-occurring neuropsychiatric features and treatment responses were extracted. A risk of bias assessment was carried by scoring the methodological quality of all case studies. Random-effects models were used to pool the data and odds ratios and 95% confidence intervals were estimated for each of the neuropsychiatric features extracted between primary and secondary psychoses groups.ResultsA total of 119 patients (62 with primary psychosis, 50 with secondary psychosis and 7 with mixed or unknown aetiology) with Fregoli syndrome were identified in the English literature. Persecutory features were more likely to occur in patients with primary Fregoli syndrome (OR = 0.26, 95% CI[0.10;0.67], p < 0.01). In addition, Fregoli syndrome in the context of a first-episode psychosis (OR = 11.00, 95% CI [2.45;49.39], p < 0.01) and in the presence of neuroimaging abnormalities (OR = 20.19, 95% CI [4.36; 93.47], p < 0.01) was significantly associated with secondary aetiology. Patients in the secondary psychosis group (n=14) showed more right hemisphere lesions than patients in the primary psychosis group (n=1), however this trend was not significant (p = 0.10). Furthermore, no statistical differences between psychoses groups were found for the demographic, clinical and neurophysiological features analysed.ConclusionsThis is the first meta-analysis investigating the features of Fregoli syndrome in primary and secondary psychosis.Findings suggest that secondary causes of Fregoli syndrome are associated with a first-episode of psychosis and that neuroimaging abnormalities, particularly in the right hemisphere, are associated with a secondary organic cause.

Objectives/AimsIn some cases, psychosis arises due to a secondary, or organic cause. Identifying these cases early on is important in ensuring these patients receive appropriate management, which may reverse the underlying cause. Determining whether the psychiatric phenotype differs in patients with an organic cause would be a major advance in the field. We sought to determine whether the presence and content of visual hallucinations was associated with an organic cause of psychosis.MethodsA meta-analysis of case-control studies was conducted. PubMed, OVID, MEDLINE, Embase, Psych INFO and Global Health databases were searched without date restrictions by two researchers using the keywords Psychos* AND Schizophreni* AND Visual hallucinat*. The inclusion criteria were a) reported frequency of visual hallucinations, b) categorisation of patients into having an organic or non-organic psychosis and c) publication in English. A random-effects model, following the DerSimonian and Laird method, was used to pool studies to generate overall odds ratios (OR) and 95% confidence intervals (CI).ResultsFifteen studies (890 organic and 955 non-organic psychosis patients) were included. Visual hallucinations were significantly associated with organic psychosis (OR = 3.17, 95% CI = 1.92, 5.24), however there was moderate between-study heterogeneity (I2 = 70%).In the 4 studies where content was reported (158 organic and 52 non-organic psychosis patients), visual hallucinations most frequently took the form of people in both organic (n = 76; 48.1%) and non-organic psychosis (n = 31; 59.6%). However, inanimate objects were significantly associated with organic psychosis (χ2(1) = 5.44, p = 0.020).ConclusionsVisual hallucinations are associated with organic psychosis. The presence of visual hallucinations, and in particular inanimate objects, may serve as a potential red flag for an organic psychosis. Findings have important clinical utility, as a simple and convenient bedside assessment to inform which patients would benefit from further neurological investigation.

AimsWe 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.BackgroundMusical hallucinations (MH) are a form of complex auditory hallucinations whereby an individual experiences an instrumental and/or vocal melody in the absence of auditory stimuli.ResultThe patient had a history of recreational drug use and a family history of psychosis. Hallucinations, which were preceded by discontinuation of alcohol and re-initiation of citalopram for depression, resolved spontaneously after three days.ConclusionAetiological factors are discussed alongside the existing literature. Whilst the underlying mechanisms underpinning musical hallucinations remains elusive, the case illustrates the potential role of alcohol withdrawal, serotonin toxicity, recreational drug use and genetic vulnerability.

Objectives This study aims i) to describe the patterns of prescription medication in functional motor disorder (mFND) treated in a Mental Health Trust, using a control group comprised of a random sample of contemporaneous patients treated in the same trust; and ii) explore the sociodemographic variables and symptoms linked to higher medication usage. Methods This is a retrospective case-control study using an electronic psychiatric case register in South London and Maudsley NHS Foundation Trust (SLaM). SLaM provides psychiatric inpatient and community services and receives national referrals for functional neurological disorder (FND) patients. Data were obtained from 322 mFND patients and 644 controls between 1stJanuary 2006 and 31st December 2016 using the ‘Clinical Records Interactive Search’ (CRIS) database. Results 247 (76.7%) mFND patients were prescribed medication, lower than 83.4% in the control group (OR: 0.59, 95% CI: 0.39–0.89, p Conclusions mFND patients are prescribed an extensive range of medications for psychiatric and somatic symptoms, most commonly anti-depressants, anti-epileptics and analgesics. The diversity in medications may be partially explained by higher rates of physical co- morbidities but may also reflect ‘somatisation’ or excessive symptom reporting combined with a lack of therapeutic options for clinicians managing patients with complex functional and ‘organic’ conditions and chronic pain. Non-essential medication prescribing may reinforce somatic illness beliefs and cause iatrogenic harm, particularly high rates of opioid pain medication, with important implications for clinical management in primary and secondary care.

Objectives/Aims Catatonia is an important neuropsychiatric disorder with a high morbidity and mortality. However, due to a perception that it is very infrequent and because of the acuity of the patients, it has remained poorly studied and research has often been confined to small groups. We aimed to establish the demographic, disease-related variables and blood-based biomarkers for catatonia in a large dataset. Methods We used the Clinical Records Interactive Search (CRIS) system hosted at the NIHR Maudsley Biomedical Research Centre to search the clinical records for patients with catatonia. An initial free-text search was refined by use of a natural language processing app. The results of the app were validated by three of the authors, who included patients in the analysis only if a clinician had made a diagnosis of catatonia and two or more items of the Bush-Francis Catatonia Screening Instrument were in evidence. Demographics, disease-related variables and blood-based biomarkers could then be extracted for these patients and compared, where relevant, to non-catatonic psychiatric patients. Results The natural language processing app extracted the records of 2766 patients with at least one mention of catatonia in their records. The majority of cases identified by the app could be validated by the researchers. A high proportion of patients had more than one episode of catatonia. Full results will be available in time for the presentation. Conclusions This study demonstrates that catatonia is not very rare, even relying on clinician identification. The frequency of recurrence is interesting, as it suggests that catatonia might indicate an underlying trait, rather than merely a transient state.

Objectives The pathoetiology of Schizophrenia remains elusive, however, a growing body of literature suggests immune dysfunction may contribute. Clozapine, an atypical antipsychotic, has superior efficacy in treatment-resistant Schizophrenia compared to other antipsychotics – however underlying mechanisms remain unknown. Clozapine has recognised immunomodulatory effects, responsible for potentially fatal haematological side-effects - such as agranulocytosis. Whether Clozapine’s immunomodulatory properties contribute toward its unique efficacy in treatment-resistant schizophrenia has not been systematically explored. Methods A retrospective cohort study design was employed to examine the relationship between white cell, neutrophil, and platelet temporal trajectories and Clozapine response in treatment-resistant schizophrenia. Eligible patients were initiated on Clozapine for the first time and continued treatment for at least twelve weeks between 2007 and 2014 within the South London and Maudsley NHS Foundation Trust, and underwent weekly haematological monitoring. Retrospective clinical ratings were performed at baseline and three months following initiation, based upon patients’ electronic clinical notes accessed through the Maudsley BRC Clinical Records Interactive Search system. Treatment response was defined as ‘much’ or ‘very much’ improved on the Clinical Global Impression – Improvement subscale. Serial cell counts were extracted from a Clozapine haematological monitoring database. Results Of 188 included patients, 114 (61%) responded to treatment. Response did not significantly vary by ethnicity or age. Mean interval between haematological assessments was 6.9 (SD 2.0) days. General linear models revealed a significant increase from baseline for all cell lines in the second treatment week (p=0.001) which persisted for three weeks (p=0.001). Group based trajectory modelling indicated that 15% of patients showed a temporary increase in white cell and neutrophil trajectories. Logistic regression revealed that treatment response was not associated with a ‘spike’ in cell count. However, females were 2.08 times more likely to respond to treatment (95% CI [1.09, 4.08], p=0.017) and 2.67 times more likely to exhibit a ‘spike’ in cell counts following Clozapine initiation (95% CI [1.14, 6.24], p=0.023). Conclusions This is the first study to examine whether Clozapine’s immunomodulatory properties contribute towards its unique efficacy. We found that clozapine was associated with an early ‘spike’ in all cell lines. Further analysis revealed a relatively small portion of patients were responsible for this transient increase. Increased cell counts did not predict Clozapine response at three months, but gender was implicated as a potential moderator variable.

ObjectiveThis study describes medication prescribing patterns in patients with motor functional neurological disorder (mFND) treated in South London and Maudsley NHS Foundation Trust (SLaM), comparing outcomes to a control group of psychiatric patients from the same hospital trust.MethodThis is a retrospective case-control study using a psychiatric case register. Cross-sectional data were obtained from 322 mFND patients and 644 psychiatry controls who had had contact with SLaM between 1st January 2006 and 31st December 2016.ResultsA slightly lower proportion of mFND patients received medication compared to controls (76.6% v. 83.4%, OR: 0.59, CI: 0.39–0.89, p p = 0.001) and had higher prescription rates of antidepressants, anti-epileptics, analgesics, and certain non-psychotropic medications. Higher numbers of prescriptions were associated with co-morbid physical conditions, and previous psychiatric admissions.ConclusionsThis is the first study to describe medication prescriptions in a large cohort of mFND patients. Patients were prescribed a wide range of psychiatric and physical health medications, with higher rates of polypharmacy than controls. Psychotropicmedication prescription is not necessarily the first line treatment for mFND, where physiotherapy and psychotherapy may be offered initially. There is limited, early-phase evidence for pharmacological therapies for mFND, and as such, the benefit-to-risk ratio of prescribing in this complex and poorly understood disorder should be carefully assessed.

Background Benign fasciculation syndrome (BFS) is characterized by persistent spontaneous contractions of muscle fibers in the absence of a pathological cause. Patients with BFS often have concerns around having motor neuron disease, in some cases fulfilling the criteria for health anxiety disorder. Research on how BFS and health anxiety relate to one another and how they should be optimally managed together is sparse. Objective We report two cases of BFS associated with health anxiety. We also review the literature on the association between BFS and health anxiety. Methods We systematically reviewed the literature using MEDLINE, Embase, PsycINFO, and OpenGrey for studies investigating benign fasciculations and anxiety up to August 2018. Results Both cases were successfully treated for health anxiety disorder with cognitive-behavioral therapy (CBT) and antidepressant medication. We identified eight studies that met the inclusion criteria, describing a total of 384 patients. Most studies were of moderate quality. Patients with BFS tended to be male and in their 30s or 40s. There was an overrepresentation of clinicians. Anxiety symptoms were common and frequently coexisted alongside fasciculations. Health anxiety was overwhelmingly focused around motor neuron disease. Conclusion A proportion of individuals with BFS experience anxiety around having motor neuron disease—to the point of developing health anxiety disorder. A bidirectional relationship may exist between BFS and health anxiety disorder. Clinicians should be alert to the possibility of health anxiety disorder in patients with BFS and have a low threshold to refer for psychiatric assessment. There is support for the role of psychological therapy, especially CBT, as well as pharmacotherapy, in the form of antidepressant medication. In severe or treatment-refractive cases, combined treatment may be indicated.

In its early stages, anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is often characterized by prominent psychiatric manifestations that can lead to delays in diagnosis and treatment. The authors aimed to address this problem by providing a detailed description of the psychiatric phenotype and demographic features that may influence presentation. Eighty-six patients with positive serum NMDAR antibodies were identified, 22 of whom met diagnostic criteria for anti-NMDAR encephalitis. Medical notes were reviewed retrospectively to rate psychiatric symptoms using standardized scales. Clinical and demographic characteristics were compared for patients with and without psychosis. Patients with psychosis exhibited severe psychopathology with a characteristic phenotype: severe and disproportionate cognitive disturbance (p

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.

Background: Epidemiological studies conducted over the past 50 years have observed an increased prevalence of psychosis among individuals with nonneurological autoimmune disorders relative to the general population, with the notable exception of rheumatoid arthritis. Whether this association reflects shared risk factors (e.g., infections or genetic liability) or a causal relationship (mediated by inflammation or brain-reactive antibodies) is yet to be determined. Quantifying the extent to which psychosis is associated with individual nonneurological autoimmune disorders may help to address this issue. A systematic review of studies investigating the comorbidity of psychosis and nonneurological autoimmune disorders was therefore conducted to clarify the nature of this association; meta-analyses were performed for individual autoimmune disorders where possible.

Neuroleptic malignant syndrome (NMS) is a potentially lethal adverse drug reaction. We report a case of NMS potentially induced by dehydration in a female patient suffering from schizoaffective disorder. We discuss possible aetiologies and triggering factors alongside the existing literature.

Background Dysregulation of the immune system represents an important vulnerability factor for schizophrenia. A rise in peripheral inflammatory markers has previously been demonstrated in psychosis; however, its significance remains uncertain. Characterising this relationship aids our understanding of the role of immunological factors in psychosis, as well as potentially identifying candidate biomarkers to guide diagnosis, treatment and prognosis. Whilst specialized inflammatory marker assays have been found to be associated with outcome and treatment, these tests are not typically available in clinical practice. We sought to establish whether routine inflammatory markers are associated with clinical characteristics and outcomes in patients with schizophrenia and related disorders. Methods A multi-site cohort study of patients admitted to an acute psychiatric ward between January 2013 and December 2016 within a large Mental Health Trust was undertaken. Cases were identified from an electronic database containing full clinical records. Inclusion criteria were patients aged 18 and 65 years with a discharge diagnosis of schizophrenia, or related disorder and a routine blood test within 3 days of admission. Exclusion criteria were diagnoses of drug-induced psychosis, organic brain disorder, or admission during the perinatal period. Pro-inflammatory (white blood cell total and differential count, C-reactive protein) and anti-inflammatory markers (albumin) recorded during the admission were extracted. Clinical characteristics were based upon the Health of the Nation Outcome Scale, a 12-item clinician rated tool contemporaneously rated at admission and discharge. Results A total of 968 patients met the inclusion criteria. 309 patients were female and mean age was 38 years. The most frequent ethnicities were White, Black African, Black Other and Black Caribbean and the commonest diagnoses were schizophrenia, unspecified non-organic psychosis and schizoaffective disorder. Mean interval from admission to admission blood test was 0.8 days. Patients with affective psychosis had a significantly higher white cell count, monocyte count and lymphocyte count than patients with non-affective psychosis on admission. Furthermore, among patients with affective psychosis, a partial correlation controlling for age, body mass index, blood pressure, physical health and smoking status found a significant association between symptom severity and monocyte count. There was a highly significant association between both neutrophil count and white cell count with hallucinatory symptoms. There was also a highly significant positive association between C-reactive protein and self-injurious behaviour, replicating recently published findings in smaller samples. There was a significant reduction in overall psychiatric symptoms over the course of admission, which was significantly associated with admission monocyte count. A partial correlation found white cell count and neutrophil count at admission were associated with reductions in hallucinatory symptoms. Eosinophil count was significantly associated with admission length. Discussion In a large cohort of patients admitted due to psychotic disorder, pro-inflammatory markers were associated with affective psychosis and overall symptom severity, and predicted admission length and reduction in symptom severity. The study supports an association between immune dysregulation and psychosis. Furthermore, the study highlights the role of routinely and inexpensively measured peripheral inflammatory markers as potential diagnostic and prognostic biomarkers in psychosis.

Objective There is interest in identifying reliable prognostic biomarkers in schizophrenia and related disorders. Serum inflammatory markers, such as white cell count and C-reactive protein (CRP), have been shown to be elevated during psychotic episodes; however, their pathogenic role is uncertain. There is limited data relating to their variability in clinical practice and relationship to clinical outcome. We have sought to investigate whether routine clinical case records contain the necessary data to further understand the relationship between serum inflammatory markers and prognosis. Method This is a retrospective case note review of patients admitted to an inner city female acute psychiatry ward. Cases were identified by reviewing electronic ward round records. Patients included had a diagnosis of non-affective, non-drug induced psychosis (schizophrenia, acute and transient psychotic disorder, persistent delusional disorder, schizotypal disorder and nonorganic psychosis) and had received a routine admission blood test. Exclusion criteria included pregnancy, significant recreational drug use prior to admission, clinical evidence of infection or history of inflammatory or haematological disease. Results A total of 20 patients met the inclusion criteria between April 2015 and October 2016. Mean age was 43 years (SD=15) and the most common ethnicities were White British (23%), Mixed Ethnicity (23%), and Caribbean (23%). The majority of cases were detained under the Mental Health Act (68%) and had previously been treated with antipsychotic medication (94%). Mean admission duration was 38 days (SD=30) and average time from admission to routine admission blood test was 4 days (SD=3 days). Admission duration was moderately positively correlated with white cell count (r=0.41, n=20, p=0.07), platelet count (r=0.40, n=20, p=0.08) and albumin (r=0.42, n=20, p=0.07). Admission duration was weakly correlated with neutrophil count (r=0.27, n=20, p=0.24) and CRP (r=−0.22, n=20, p=0.35). When patients split according to those above and below the median admission length, patients with longer admissions had significantly higher platelet count (p Conclusion This small retrospective review suggests that in routine clinical case practice information is collected which could be used to explore the role of inflammatory markers as prognostic biomarkers in patients with schizophrenia and related disorders. Despite our extremely small sample we have found a positive correlation between platelet count and admission length. However this needs to be considered in the presence of multiple confounders. Use of electronic patient databases may be helpful in extending the sample to formally establish any prognostic relationships.

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