Tag: Clozapine

An Overview of the National Psychosis Unit

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Introduction

The National Psychosis Unit is a national treatment centre for patients with schizophrenia and other psychotic disorders, in the United Kingdom. The unit is a tertiary referral centre in the National Health Service. It is located at the Bethlem Royal Hospital, part of the South London and Maudsley NHS Foundation Trust. It is closely affiliated to the Institute of Psychiatry, King’s College London, and forms part of the Psychosis Clinical Academic Group of King’s Health Partners.

Brief History

The Unit was set up in the early 1990s. It was one of the first units in the UK to offer the antipsychotic drug clozapine, following its reintroduction in the UK in 1990.

Staff

The service has a multidisciplinary team of doctors, nurses, pharmacists and psychologists, many of whom work part of their time as clinical scientists and researchers, investigating the causes of psychotic disorders, and the effectiveness of both existing and new treatments.

Sir Robin Murray, Professor of Psychiatric Research at the Institute of Psychiatry at King’s College London, is a prominent member of staff at National Psychosis Unit.

Treatment

The National Psychosis Unit specialises in evidence-based treatment for people with schizophrenia, bipolar disorder and other similar disorders, particularly where local treatment has been unsuccessful or only partially successful in relieving symptoms. Anyone receiving NHS treatment can access the service free of charge following a referral by the person’s psychiatrist or general practitioner

The service provides second opinions on medication, diagnosis or any other aspect of care. The service has an outpatient clinic and 24-bedded inpatient facility. As well as pharmaceutical treatments, there is a strong focus on psychological treatments, rehabilitation and recovery, and reducing the risk of readmission through exploring what has led to breakdowns in the past and how to avoid this happening in future. The Unit also hosts research into the treatment of psychosis, including clinical trials of new treatments for psychosis. The National Psychosis Carers’ Group, which meets monthly, supports the carers and families of people with psychosis and allows them a forum for discussion.

Links with Other Organisations

The National Psychosis Unit has strong links with the Department of Psychosis Studies at the Institute of Psychiatry, King’s College London. The Unit also has longstanding links with mental health charities, including Rethink and SANE.

Awards

The Unit won the Hospital Doctor Psychiatric Team of the Year Award in 1997.

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Does Lack of a Consistent Definition Hinder Treatment for Clozapine-Resistant Schizophrenia Patients?

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Research Paper Title

Characteristics and definitions of ultra-treatment-resistant schizophrenia – A systematic review and meta-analysis.

Background

The aim of this systematic review and meta-analysis was to characterise ultra-treatment-resistant Schizophrenia also known as clozapine-resistant schizophrenia (CRS) patients across clozapine combination and augmentation trials through demographic and clinical baseline data. Furthermore, the researchers investigated the variability and consistency in CRS definitions between studies.

Methods

Systematic searches of articles indexed in PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and PsycINFO were conducted in March 2020. 1541 randomised and non-randomised clinical trials investigating pharmacological and non-pharmacological clozapine add-on strategies were screened and a total of 71 studies were included. The primary outcome was the overall symptom score at baseline, measured with Positive and Negative Syndrome Scale (PANSS) total or Brief Psychiatric Rating Scale (BPRS) total scores.

Results

Data from 2731 patients were extracted. Patients were overall moderately ill with a mean PANSS total score at baseline of 79.16 (±7.52), a mean duration of illness of 14.64 (±4.14) years with a mean clozapine dose of 436.94 (±87.47) mg/day. Illness severity data were relatively homogenous among patients independently of the augmentation strategy involved, although stark geographical differences were found. Overall, studies showed a large heterogeneity of CRS definitions and insufficient guidelines implementation.

Conclusions

This first meta-analysis characterising CRS patients and comparing CRS definitions revealed a lack of consistent implementation of a CRS definition from guidelines into clinical trials, compromising the replicability of the results and their applicability in clinical practice. The researchers offer a new score modelled on a best practice definition to help future trials increase their reliability.

Reference

Campana, M., Falkai, P., Siskind, D., Hasan, A. & Wagner, E. (2021) Characteristics and definitions of ultra-treatment-resistant schizophrenia – A systematic review and meta-analysis. Schizophrenia Research. 228, pp.218-226. doi: 10.1016/j.schres.2020.12.002. Online ahead of print.

Schizophrenia: Clozapine Treatment & Haematological Changes

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Research Paper Title

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 haematological 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. Haematological 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 haematological factors assessed at baseline, nor changes in these factors, were directly associated with treatment response.

Conclusions

Clozapine treatment is associated with transient haematological changes during the first month of treatment; however, there was no evidence that these were related to the therapeutic response.

Reference

Blackman, G., Lisshammer, J.E.L., Zafar, R., Pollak, T.A., Prutchard, M., Cullen, A.E., Rogers, J., Carter, B., Griffiths, K., Nour, M., David, A.S., McGuire, P., Stewart, R. & MacCabe, J. (2020) Clozapine Response in Schizophrenia and Hematological Changes. Journal of Clinical Psychopharmacology. 41(1):19-24. doi: 10.1097/JCP.0000000000001329.

Clozapine & Motivation for Food

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Research Paper Title

Clozapine reliably increases the motivation for food: parsing the role of the 5-HT2c and H1 receptors.

Background

Although clozapine is effective in treating schizophrenia, it is associated with adverse side effects including weight gain and metabolic syndrome.

Despite this, the role of clozapine on feeding behaviour and food intake has not been thoroughly characterised.

Clozapine has a broad pharmacological profile, with affinities for several neurotransmitter receptors, including serotonin (5-hydroxytriptamine, 5-HT) and histamine.

Given that the serotonin 5-HT2C receptor and histaminergic H1 receptor are involved in aspects of feeding behaviour, the effect of clozapine on feeding may be linked to its action at these receptors.

Methods

The researchers assessed, in rats, the effect of acute and subchronic administration of clozapine on responding for food under a progressive ratio (PR) schedule under conditions of food restriction and satiety.

They also examined the effect of antagonists of the serotonin 5-HT2C and histaminergic H1 receptors on the same schedule.

Results

Clozapine reliably increased responding for food, even when rats had ad libitum access to food.

The effect of clozapine on responding for food was reproduced by combined (but not individual) antagonism of the serotonin 5-HT2C and histaminergic H1 receptors.

Conclusions

These findings show that clozapine enhances the motivation to work for food, that this effect is stable over repeated testing, and is independent of hunger state of the animal.

This effect may relate to a combined action of clozapine at the serotonin 5-HT2C and histaminergic H1 receptors.

Reference

Abela, A.R., Ji, X.D., Li, Z., Lê, A.D. & Fletcher, P.J. (2020) Clozapine reliably increases the motivation for food: parsing the role of the 5-HT2c and H1 receptors. Psychopharmacology (Berl). doi: 10.1007/s00213-019-05425-7. [Epub ahead of print].

Utility of Add-on Mirtazapine to Clozapine-Responsive Early-Onset Schizophrenia

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Research Paper Title

Add-on mirtazapine to clozapine-responsive early-onset schizophrenia.

Abstract

Early-onset schizophrenia is notorious for poor prognostication and treatment-refractoriness.

Clozapine remains a viable option, albeit off-label, but is clearly underutilised in this population.

Use is typically fraught with panoply of drastic side effects.

Here, the authors report on an adolescent case with schizophrenia that responded ultimately to clozapine.

Add-on mirtazapine was advantageous spanning negative and cognitive symptom domains whilst addressing clozapine-related sialorrhea and urinary incontinence.

This might open new venues for such complicated clinical scenarios.

Reference

Moodliar, S., Naguy, A. & Elsori, D.H. (2019) Add-on mirtazapine to clozapine-responsive early-onset schizophrenia. Psychiatry Research. https://doi.org/10.1016/j.psychres.2019.112701.