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Risk of death with antipsychotics ‘varies two-fold’

The use of some antipsychotics in elderly patients is ‘not justified' because of the risk of harm to patients, researchers have concluded, after a major new study found the risk of death with different medications varies two-fold.

The large analysis of patients in nursing homes – published today in the British Medical Journal – looked at 75,500 new users of antipsychotics aged 65 years or older. Over five years it found haloperidol had double the risk of mortality compared with the most commonly used antipsychotic, risperidone.

In contrast, users of quetiapine had a 19% reduced risk of death compared with risperidone.

The effects were strongest shortly after the start of treatment, remained after adjustment for dose, and were seen for all causes of death examined. No clinically meaningful differences were observed for other antipsychotics.

The US researchers – from Brigham and Women's Hospitalin Boston and Colombia University – admitted the use of antipsychotics ‘could not be justified as evidence-based' but suggested doctors could use the study to inform their prescribing.

The researchers concluded: ‘The evidence accumulated so far implies that the use of haloperidol in this vulnerable population cannot be justified, because of the excess harm.'

‘Quetiapine might be somewhat safer than other atypical drugs, but these findings require replication in other studies.'

In an editorial, Dr Jenny McCleery, consultant psychiatrist at Oxford Health NHS Foundation Trust and Dr Robin Fox, a GP in Bicester, Oxfordshire, warned that this new information on risk must be weighed against the potential benefits of the drugs.

They said: ‘There is no high quality evidence that quetiapine is effective for treating neuropsychiatric symptoms in dementia, and the results of the current study should not support its use.'

Professor David Nutt, professor of neuropsychopharmacology at Imperial College London, said: ‘It's good to have a more fine-grained analysis of the relative effects of these different compounds. This should help direct safer and more rational prescribing.'

‘However, more research is required before we really understand the reasons for these differences, which are likely to relate to the different receptor interactions of these drugs, which vary a great deal, particularly as quetiapine [the safest] has the shortest half-life.'

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