Clozapine: A Clinical Review of Adverse Effects and Management

Iqbal, Mohammad; Rahman, Atiq; Husain, Zahid; Mahmud, Syed Zaber; Ryan, W. H.; Feldman, Jacqueline

doi:10.3109/10401230309085668

Cited by 168 publications

(99 citation statements)

References 29 publications

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“…37 It produces few acute EPS and has a lower incidence of tardive dyskinesia (TD) than other antipsychotics, although other ADRs include sedation, hypersalivation and hypertension. [44][45][46] Regarding efficacy, the HTA review of atypical antipsychotics in schizophrenia 47 noted that evidence for the effectiveness of the atypicals compared with typicals was 'in general of poor quality, based on short term trials and difficult to generalise to the whole population of people with schizophrenia'. The more recent Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) 43 and Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS) trials 48 have led the chief investigators of these trials to conclude that typical antipsychotics are as good as atypical antipsychotics for many patients.…”

Section: Schizophreniamentioning

confidence: 99%

The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation

Fleeman

McLeod²,

Bagust³

et al. 2010

Health Technol Assess

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How to obtain copies of this and other HTA programme reports An electronic version of this title, in Adobe Acrobat format, is available for downloading free of charge for personal use from the HTA website (www.hta.ac.uk). A fully searchable DVD is also available (see below).Printed copies of HTA journal series issues cost £20 each (post and packing free in the UK) to both public and private sector purchasers from our despatch agents.Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is £2 per issue and for the rest of the world £3 per issue. How to order:-fax (with credit card details) -post (with credit card details or cheque) -phone during office hours (credit card only).Additionally the HTA website allows you to either print out your order or download a blank order form. Contact details are as follows:Synergie UK (HTA Department) Digital House, The Loddon Centre Wade Road Basingstoke Hants RG24 8QW Email: orders@hta.ac.uk Tel: 0845 812 4000 -ask for 'HTA Payment Services' (out-of-hours answer-phone service) Fax: 0845 812 4001 -put 'HTA Order' on the fax header Payment methods Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to University of Southampton and drawn on a bank with a UK address. Paying by credit cardYou can order using your credit card by phone, fax or post. SubscriptionsNHS libraries can subscribe free of charge. Public libraries can subscribe at a reduced cost of £100 for each volume (normally comprising 40-50 titles). The commercial subscription rate is £400 per volume (addresses within the UK) and £600 per volume (addresses outside the UK). Please see our website for details. Subscriptions can be purchased only for the current or forthcoming volume. How do I get a copy of HTA on DVD?Please use the form on the HTA website (www.hta.ac.uk/htacd/index.shtml). HTA on DVD is currently free of charge worldwide.The website also provides information about the HTA programme and lists the membership of the various committees. HTA NIHR Health Technology Assessment programmeT he Health Technology Assessment (HTA) programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care. The research findings from the HTA programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the 'National Knowledge Service'. The HTA programme is needs led in that it fills gaps in the evidence needed by the NHS. There are three routes to the start of projec...

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Section: Schizophreniamentioning

confidence: 99%

The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation

Fleeman

McLeod²,

Bagust³

et al. 2010

Health Technol Assess

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“…The affinity of clozapine for 5-HT receptors is also high, with a 5-HT 2 receptor occupancy of 84% to 94% at doses of 125 to 400 mg. 24 Limbic region D 4 Limbic region a Based on Beng-Choon et al 5 The use of clozapine is primarily limited by the risk of agranulocytosis, defined as a granulocyte count of < 500/mm 3 . 21 Data collected from more than 11,000 patients through the Clozaril Patient Management System indicate that the incidence of agranulocytosis was 0.80% at 1 year. 27 In general, agranulocytosis appears to occur within the first 3 months of therapy, with the risk peaking by the third month.…”

Section: Clozapinementioning

confidence: 99%

“…16 It is classified as a dibenzothiazepine derivative and is known to be particularly effective in patients who do not respond to conventional or other atypical antipsychotics. 16,21 The effective dosage range is 300 to 600 mg/day, but dosages of up to 900 mg/day may be needed in some patients. 16 Clozapine fits all of the proposed definitions of atypicality.…”

Section: Clozapinementioning

confidence: 99%

Atypicality of Atypical Antipsychotics

Farah¹

2005

Prim. Care Companion CNS Disord.

112

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Objective: To review the current definition of atypicality, discuss the unique features of each atypical antipsychotic, and determine whether the available drugs in this class really meet the classical definition of atypicality.Data Sources: A PubMed search was conducted to identify literature on the subject of this review, supported by additional articles based on the author's clinical knowledge and experience.Study Selection and Data Extraction: Relevant references were extracted and summarized in order to meet the objective of the article.Data Synthesis: Atypical antipsychotics are considered a major advance over conventional antipsychotics, primarily because they offer effective treatment alternatives that are relatively free of extrapyramidal symptoms. In fact, the term atypicality was originally used to describe antipsychotic agents with a minimal risk of causing extrapyramidal symptoms. However, over the years the definition has been modified such that there is currently no consensus on a true definition of atypicality for these agents. Each of the atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) commercially available in the United States is unique in terms of its pharmacologic profile, differing with respect to receptor-binding affinity, mechanism of action, and adverse events. Of the available atypical antipsychotics, clozapine and quetiapine have shown the lowest propensity to cause extrapyramidal symptoms. Although the risk of extrapyramidal symptoms is lower with risperidone and olanzapine than with conventional antipsychotics, risk increases with dose escalation. Data for ziprasidone indicate that the risk of extrapyramidal symptoms may be similar to that of risperidone and olanzapine. There is a concern of akathisia with aripiprazole; however, more experience with this agent is needed before definitive conclusions are made.Conclusion: If the definition of "atypical" antipsychotic is considered to be freedom from extrapyramidal symptoms, then, based on a comprehensive review of available data and clinical experience, clozapine and quetiapine appear to be the only true atypicals.( Prim Care Companion J Clin Psychiatry 2005;7:268-274)

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“…However, clozapine has a 1% incidence rate of agranulocytosis and a 3% incidence rate of neutropenia (Atkin et al, 1996, Alvir et al, 1993, potentially lethal systemic side effects which limit its use. It has been reported that even among the patients who will consent to use clozapine, 17% discontinue use due to systemic side effects (Iqbal et al, 2003). Design of a less-toxic clozapine has been a pharmaceutical development goal for the last 25 years.…”

Section: Introductionmentioning

confidence: 99%

“…Transdermal atypical antipsychotics currently under development may improve compliance, eliminate the pain of IM injections, and permit abrupt discontinuation, but are still limited by constant dosing, and more importantly, unaltered peripheral side effect profile. These side effects are the most profoundly limiting issue in antipsychotic administration, reducing patient acceptance of the medication, potentially resulting in patient illness (e.g., liver toxicity and cardiac conduction deficits) (Lublin et al 2005;Iqbal et al 2003;Miller 2000) and mortality (e.g., bone marrow failure).…”

Section: Introductionmentioning

confidence: 99%

An initial animal proof-of-concept study for central administration of clozapine to schizophrenia patients

Abrams¹,

Zheng²,

Choo³

et al. 2008

Schizophrenia Research

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While clozapine is the acknowledged superior pharmacotherapeutic for the treatment of schizophrenia, the side effect profile, which includes potentially fatal complications, limits its usefulness. Central administration of clozapine directly into the brain could circumvent many of the side effect issues due to the dramatic reduction in dose and the limitation of the drug primarily to the CNS. The present study demonstrates that clozapine can be formulated as a stable solution at physiological pH, which does not have in vitro neurotoxic effects at concentrations which may be effective at treating symptoms. Acute central administration improved auditory gating deficits in a mouse model of schizophrenia-like deficits. Assessment of behavioral alterations in rats receiving chronic central infusions of clozapine via osmotic minipump were performed with the open field and elevated plus mazes. Neither paradigm revealed any detrimental effects of the infusion. While these data represent only an initial investigation, they none-the-less suggest that central administration of clozapine may be a viable alternate therapeutic approach for schizophrenia patients which may be effective in symptom reduction without causing behavioral or neurotoxic effects.

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Clozapine: A Clinical Review of Adverse Effects and Management

Cited by 168 publications

References 29 publications

The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation

The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation

Atypicality of Atypical Antipsychotics

An initial animal proof-of-concept study for central administration of clozapine to schizophrenia patients

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