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      Clozapine rechallenge and initiation despite neutropenia- a practical, step-by-step guide

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          Abstract

          Clozapine remains the only drug treatment likely to benefit patients with treatment resistant schizophrenia. Its use is complicated by an increased risk of neutropenia and so there are stringent monitoring requirements and restrictions in those with previous neutropenia from any cause or from clozapine in particular. Despite these difficulties clozapine may yet be used following neutropenia, albeit with caution. Having had involvement with 14 cases of clozapine use in these circumstances we set out our approach to the assessment of risks and benefits, risk mitigation and monitoring with a practical guide.

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          Most cited references 59

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          The Leucocytosis of Exercise

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            A systematic review of the evidence of clozapine's anti-aggressive effects.

            Reducing the risk of violent and aggressive behaviour in patients with schizophrenia remains a clinical priority. There is emerging evidence to suggest that the second-generation antipsychotic, clozapine, is effective at reducing this risk in patients with schizophrenia and some evidence to suggest that it may be best in selected patients. We conducted a systematic literature search in March 2011 of all prospective and retrospective studies, which investigated clozapine's anti-aggressive effects in a variety of mental disorders. The review identified six animal studies, four randomized controlled trials, 12 prospective non-controlled studies and 22 retrospective studies, with four case studies. We found considerable evidence in support of clozapine's ability to reduce violent and aggressive behaviour. Clozapine's anti-aggressive effect was most commonly explored in patients with schizophrenia, with less evidence available for other psychiatric disorders, including borderline personality disorder, autistic spectrum disorders, post-traumatic stress disorder, bipolar disorder and learning disability. There was mixed evidence to address the question of whether or not clozapine was any more effective than other antipsychotics. In the case of schizophrenia, there was evidence to suggest that clozapine's anti-aggressive effect was more marked particularly in those with treatment-resistant illness. Its anti-aggressive effects appeared to be 'specific', being to some extent greater than both its more general antipsychotic and sedative effects. There were significant methodological inconsistencies in the studies we identified, particularly surrounding patient recruitment criteria, the definition and measurement of violence and the lack of randomized, controlled trials. Data on therapeutic monitoring were also limited. Clozapine can reduce violence and persistent aggression in patients with schizophrenia and other psychiatric disorders. It may offer an advantage over other antipsychotics, although perhaps exclusively in the case of traditionally defined 'treatment resistance' or more broadly defined 'complex cases' with co-morbidity. Larger, randomized, blinded, controlled studies with robust characterization of participants, and standardized measures of violence and aggression are, however, needed to fully understand this link and explore the possible mechanisms.
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              Meta-analysis examining the epidemiology of clozapine-associated neutropenia.

               N. Myles,  H. Myles,  S Xia (2018)
              Clozapine is associated with life-threatening neutropenia. There are no previous meta-analyses of the epidemiology of clozapine-associated neutropenia.
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                Author and article information

                Contributors
                ed.silva@nhs.net
                Journal
                BMC Psychiatry
                BMC Psychiatry
                BMC Psychiatry
                BioMed Central (London )
                1471-244X
                5 June 2020
                5 June 2020
                2020
                : 20
                Affiliations
                [1 ]GRID grid.439410.b, ISNI 0000 0000 8608 0320, Consultant Forensic Psychiatrist, , Ashworth Hospital, Mersey Care NHS Foundation Trust, ; Parkbourn, Maghull, Merseyside, L31 1HW UK
                [2 ]GRID grid.439372.8, ISNI 0000 0004 0641 7667, Consultant Haematologist, , Arrowe Park Hospital, ; Arrowe Park Road, Upton, Merseyside, Wirral CH49 5PE UK
                Article
                2592
                10.1186/s12888-020-02592-2
                7275543
                32503471
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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