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      Clozapine: a review of clinical practice guidelines and prescribing trends

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          Abstract

          Background

          Clozapine effectiveness in the treatment of refractory schizophrenia has been sustained by published evidence in the last two decades, despite the introduction of safer options.

          Discussion

          Current clinical practice guidelines have strongly recommended the use of clozapine in treatment-resistant schizophrenia, but prescribing trends do not appear to have followed such recommendations. Clozapine is still underutilized especially in patients at risk of suicide. It seems that physicians are hesitant in prescribing clozapine due to concerns about serious adverse effects. Recent reports have highlighted the need to inform health professionals about the benefits of treating patients with clozapine and have voiced concerns about the underutilization of clozapine especially in patients at risk of suicide.

          Summary

          Guidelines and prescribing patterns reported in various countries worldwide are discussed. Suggestions on how to optimize clozapine utilization have been published but more efforts are needed to properly inform and support prescribers’ practices.

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          Most cited references 52

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          The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements.

          In light of the large number of studies published since the 2004 update of Schizophrenia Patient Outcomes Research Team psychopharmacological treatment recommendations, we conducted an extensive literature review to determine whether the current psychopharmacological treatment recommendations required revision and whether there was sufficient evidence to warrant new treatment recommendations for prespecified outcomes of interest. We reviewed over 400 articles, which resulted in 16 treatment recommendations: the revision of 11 previous treatment recommendations and 5 new treatment recommendations. Three previous treatment recommendations were eliminated. There were 13 interventions and/or outcomes for which there was insufficient evidence for a treatment recommendation, and a statement was written to summarize the current level of evidence and identify important gaps in our knowledge that need to be addressed. In general, there was considerable consensus among the Psychopharmacology Evidence Review Group and the expert consultants. Two major areas of contention concerned whether there was sufficient evidence to recommend specific dosage ranges for the acute and maintenance treatment of first-episode and multi-episode schizophrenia and to endorse the practice of switching antipsychotics for the treatment of antipsychotic-related weight gain. Finally, there continue to be major gaps in our knowledge, including limited information on (1) the use of adjunctive pharmacological agents for the treatment of persistent positive symptoms or other symptom domains of psychopathology, including anxiety, cognitive impairments, depressive symptoms, and persistent negative symptoms and (2) the treatment of co-occurring substance or medical disorders that occur frequently in individuals with schizophrenia.
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            Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.

            When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation. Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]). Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation. For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.
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              Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology.

               Thomas R E Barnes,   (2011)
              These guidelines from the British Association for Psychopharmacology address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting, involving experts in schizophrenia and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from the participants and interested parties, and cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. The practice recommendations presented are based on the available evidence to date, and seek to clarify which interventions are of proven benefit. It is hoped that the recommendations will help to inform clinical decision making for practitioners, and perhaps also serve as a source of information for patients and carers. They are accompanied by a more detailed qualitative review of the available evidence. The strength of supporting evidence for each recommendation is rated.
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                Author and article information

                Contributors
                Journal
                BMC Psychiatry
                BMC Psychiatry
                BMC Psychiatry
                BioMed Central
                1471-244X
                2014
                7 April 2014
                : 14
                : 102
                Affiliations
                [1 ]Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, Canada
                Article
                1471-244X-14-102
                10.1186/1471-244X-14-102
                3999500
                24708834
                Copyright © 2014 Warnez and Alessi-Severini; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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