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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.

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.

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.

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

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.

A survey of magic mushroom use was completed by 174 participants in 2004, a year when the sale of hallucinogenic mushrooms was not illegal in the UK. The data were collected in Edinburgh and Bristol (UK). Participants were a self-selecting convenience sample. Participants tended to be in their 20s, White-British, in education or employed; 64% were male. Participants reported a pattern of infrequent but intense consumption (47% used between 4-12 times/year, average consumption in one setting was 12 g, a high dose). Use was explained in terms of laughing, hallucinations, altering perspective (41-74%), and feelings of being closer to nature (49%). Negative experiences reported included paranoia (35%) and anxiety (32%). Mushroom use was located within a wider recreational drug and alcohol culture. Four focus groups aided the interpretation of the data. Future research is recommended into negative experiences. Implications for policy and harm minimisation literature are discussed.