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Craven, Harrogate and Rural District Primary CareTrust, 2 Dragon Parade, Harrogate HG1 5BY, e-mail: Gcirulli{at}btopenworld.com
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Abstract |
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Clozapine is an effective drug in treatment-resistant schizophrenia, but it seems to be prescribed for few patients under the age of 18 years. This study reports a survey of consultant psychiatrists working in adolescent units in the UK, looking at their use of clozapine and experience with it.
RESULTS
Out of 83 clinicians, 59 responded (71%). More than 40% of respondents do not use clozapine, and those who do may not always be following best practice recommendations. Reasons for not using clozapine, beliefs about its effectiveness and problems encountered in its use are described.
CLINICAL IMPLICATIONS
Clozapine may not always be made available to young people with treatment-resistant schizophrenia. There is a need for more education, guidance and debate on clozapine use in child and adolescent psychiatry.
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Introduction |
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Delay in treatment is associated with poorer results, whereas early intervention appears beneficial: the longer the duration of untreated psychosis the worse the condition becomes, with functional outcome appearing to decline sharply (Joyce et al, 2002; Harrigan et al, 2003). Early treatment thus has the potential to reduce the secondary impacts of this serious mental illness such as suicide, stigma, isolation and reduction in social status (Duggan et al, 2003; Meltzer & Baldessarini, 2003).
Clozapine is the only drug licensed for the treatment of schizophrenia in individuals as young as 16 years who are unresponsive to or intolerant of conventional medication. In the summary of product characteristics by Novartis non-responsiveness is defined as a lack of satisfactory clinical improvement despite the use of adequate doses of at least two marked neuroleptics prescribed for adequate duration. Intolerance is defined as the impossibility to achieve adequate benefits with conventional neuroleptic drugs because of severe and untreatable neurological adverse reactions (extrapyramidal symptoms or tardive dyskinesia).
The use of clozapine is affected by several possible complications. Fits, excess salivation, drowsiness, weight gain and autonomic side-effects (blurring of vision, increased intra-ocular pressure, constipation and urinary retention) are the most common (Frazier et al, 2003; British Medical Association & Royal Pharmaceutical Society of Great Britain, 2004). Patients taking clozapine also need regular blood tests, supervised at the time of starting this study only by the Clozaril Patient Monitoring Service. In the UK this system, available 24 h a day, was originally developed in 1990 to manage the risk of agranulocytosis associated with clozapine. It requires the patients, the responsible physicians and the supplying pharmacies to be registered with the service. This ensures that people who develop severe complications are identified early and that they are not exposed to the drug again in the future, if it has to be discontinued (Atkin & OSullivan, 1995). In addition, for patients under 18 years old taking clozapine, the advice from the original manufacturer (Novartis) is that they should have an electroencephalogram (EEG) prior to starting treatment and at regular intervals during the course of treatment owing to the increased incidence of absences and seizures (Freedman et al, 1994; Fink, 2002).
According to the Clozaril Patient Monitoring Service, in April 2004, out of more than 21 000 patients on the register, there were just 88 patients under the age of 18 years in the UK. This is such a small number that it is possible that young people are not being offered treatment with clozapine. This would not only contravene the National Institute for Clinical Excellence guidance on atypical antipsychotics, which states that in individuals with evidence of treatment resistant schizophrenia clozapine should be introduced at the earliest opportunity (National Institute for Clinical Excellence, 2002), but it would also deprive patients of a potentially unique and effective treatment. Some studies in fact suggest that its use might be worthwhile and beneficial in children and young people (Kumra et al, 1996; MacEwan & Morton, 1996; Turetz et al, 1997).
Thus there is accumulating evidence to advocate the early use of clozapine, although this medication has the potential to cause severe side-effects. This paper reports the results of a survey of the attitudes and prescribing practices related to clozapine in a sample of consultants in adolescent psychiatry.
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Method |
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| Box 1. Study questionnaire: respondents were asked to tick statements
that reflected what happened in their practice
ECG, electrocardiogram; EEG, electroencephalogram.
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The population sampled comprised all consultant psychiatrists working in adolescent units in the UK. Contact details were obtained from the unit directory of the Royal College of Psychiatrists. All of the 83 practitioners eligible to take part were contacted. The questionnaire was anonymous; no attempt was made to identify the respondent consultants and there was no request for information regarding individual patients. The project was submitted to and approved by the South Sheffield research ethics committee.
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Results |
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Participants were asked about side-effects and other problems encountered when using clozapine. The most common side-effects reported were drowsiness, reported by 25 (73%) of respondents using this drug; hypersalivation, 23 (68%); hypotension, 11 (32%); constipation, 11 (32%); and others, including urinary problems, weight gain, tachycardia, diabetes and absences/seizures, reported by 7 (21%). A number of these doctors described difficulties with prescribing this drug for young people, citing poor adherence to treatment, particularly because of the risk of weight gain. Reductions in white cell count had been experienced by 18 of the 34 respondents (53%); 7 (21%) reported having to stop clozapine because of other serious problems such as myocarditis, arrhythmias, excessive sedation, untreatable hypersalivation, overdose and lack of adherence. Twenty-six (76%) found the patient monitoring service useful in managing their prescribing.
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Discussion |
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The data from this survey suggest that a considerable number of specialists in adolescent psychiatry working in in-patient units do not prescribe clozapine. Unfamiliarity with the drug and the need for monitoring of side-effects seem to influence its use, and it might be that clearer information about effectiveness and prescribing practices would result in increased usage. The need for information and training is emphasised by the fact that those who do use clozapine may not comply with nationally agreed recommendations about prescribing: for example, many do not seem to routinely request EEGs before or during the course of treatment.
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Acknowledgments |
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References |
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