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Sunday, 3 December, 2000, 01:14 GMT
Schizophrenia drug dispute intensifies
schizoprehnia brain image
Dabate continues over drugs for schizophrenia
The debate over which drugs should be prescribed for patients with schizophrenia has been rekindled after the publication of a controversial paper.

Experts are divided over the merits of a relatively new and expensive class of drugs, known as atypical antipsychotics.

There is a consensus that these drugs, including risperidone, clozapine and olanzapine, cause considerably fewer side-effects than older antipsychotics such as haloperidol.

But, where the dispute arises is whether the atypicals should routinely be prescribed to someone diagnosed with schizophrenia - and that dispute seems to be becoming increasingly bitter.
Conventional antipsychotics
  • haloperidol
  • chlorpromazine
  • Patient groups and some doctors argue that the atypicals can offer a much improved quality of life for people with schizophrenia and their families.
    Atypical antipsychotics
  • amisulphride
  • clozapine
  • olanzapine
  • quetiapine
  • risperidone
  • sertindole
  • Certainly, the side-effects of the older drugs, such as uncontrollable shaking and depression, are intolerable for some.

    But academics have said that there is not enough evidence from drug trials to convince them that the newer - and more expensive - drugs should be the first choice for doctors deciding what to prescribe.

    Refinement not revolution

    At the end of 1999, the NHS Centre for Review and Dissemination at the University of York, published one of its effective health care bulletins - a review of treatments and recommendations about how they should be used in the NHS.

    The conclusion was that the atypical antipsychotics "may be a further refinement, but not a revolution, in the care of those with schizophrenia".

    The bottom line was that more research needed to be done to make a convincing argument that the NHS should fund use of atypicals in everyday practice.

    In the meantime, the National Institute for Clinical Excellence has also been asked to review schizophrenia drugs and recommend which ones should be used - though those recommendations may be more than a year away.

    Many of the perceived benefits of atypical antipsychotics are really due to excessive doses of the comparator drug used in the trials

    Dr John Geddes, University of Oxford

    But, a year on from York's analysis of the atypicals, a paper has been published in the British Medical Journal, following a similar review of the trials that have been conducted into their use.

    Among the co-authors of the paper is Nick Freemantle from the University of York, together with John Geddes and Paul Harrison from the Department of Psychiatry at Oxford University.

    After reviewing the research on atypicals published up until 1999 they conclude that "there is no clear evidence that atypical antipsychotics are more effective or are better tolerated than conventional antipsychotics".

    They say that "taking trial results at face value" the newer drugs seem to be more effective and better tolerated with fewer side effects.

    But they believe that "many of the perceived benefits of atypical antipsychotics are really due to excessive doses of the comparator drug used in the trials".

    Side effects are common with older drugs
    They advocate prescribing the older drugs unless the side-effects are so severe they can not be tolerated.

    The article has caused a storm in the medical community and from patient groups - not just because of its conclusions but how it reached them.

    The National Schizophrenia Fellowship, together with MIND and the Manic Depression Fellowship, is due to release findings from its own research among 2,600 people using antipsychotic in the next few days.

    The overall conclusion from patients' experiences is that atypicals are better, though they too have side-effects, such as weight gain.

    Offer patients choice

    "What we believe is that people should not be denied the choice - if you have a drug that has side-effects and one that doesn't, then you don't set out to do harm to your patient, regardless of the cost," NSF spokesman Paul Corry said.

    The Parkinson's-like symptoms associated with older antipsychotics, as well as being intolerable for many also contribute to poor compliance, he pointed out.

    The paper was, he said, a result of "bad science" with the conclusions not supported by the data the researchers looked at.

    This view is supported by David Taylor, chief pharmacist at the Maudsley Hospital in London.

    The Maudsley produces its own guidance on schizophrenia treatments, which is widely used by clinicians around the country.

    The most recent version, published in October 2000 recommends that all schizophrenia patients should be prescribed the atypical anti-psychotics.

    You have got people who are frightened and disturbed and what they are saying is risk it and give them a drug which has an unacceptable burden of side-effects

    Dr David Taylor, Maudsley Hospital
    Dr Taylor challenges the view that the older drugs can be given in doses that will help schizophrenia symptoms without causing unwanted side-effects.

    "I really don't think such a dose exists - people haven't been able to find it in the 48 years the drugs have been around - and the data doesn't bear it out," he told BBC News Online

    "If people follow the advice given in this paper then in all probability patients will suffer.

    "You have got people who are frightened and disturbed and what they are saying is risk it and give them a drug which has an unacceptable burden of side-effects even at low doses."

    He said there are patients who may not want the weight gain side-effects of the atypicals, but it was important to offer patients choice.

    Dr Clive Adams, head of the Cochrane schizophrenia group, which reviews data on treatments said his team would also be looking closely at the BMJ article.

    "For now it seems likely to confuse matters rather than clarify them," he said.

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