NPC Archive Item: Short-term serious adverse effects of antipsychotics in people with dementia

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Rochon PA, Normand S-L, Gomes T, et al. Antipsychotic therapy and short-term serious events in older adults with dementia. Arch Intern Med. 2008;168:1090–6

Even short-term prescribing of antipsychotics (conventional or atypical) in people with dementia increases the risk of serious adverse events

Do not prescribe any antipsychotics for people with dementia routinely for the control of behaviours that challenge, even if it is just for short-term use. Any use should be by specialists only, and after full consideration of the risks and benefits.

The NICE guideline recommends that people with dementia who develop non-cognitive symptoms or behaviours that challenge should be offered a pharmacological intervention in the first instance only if they are severely distressed or there is an immediate risk of harm to the person or others. Antipsychotics should only be offered after a full discussion with the patient and/or their carers about the risks and benefits, especially the risk of stroke/TIA and possible adverse effects on cognition. The dose of antipsychotic should be low initially and titrated upwards. It should be treatment time-limited and regularly reviewed (every three months or according to need). Antipsychotics should not be prescribed to people with mild-to-moderate dementia with Lewy bodies, as these people are particularly at risk of serious adverse effects.

What is the background to this?
Antipsychotics have been used frequently in the past for the treatment of behavioural and psychological symptoms of dementia. As pointed out in a MeReC Bulletin on the Treatment of Dementia any modest efficacy is offset by the possibility of adverse effects, which can be serious and require discontinuation, and may even be fatal.

In March 2004, the Committee on Safety of Medicines (CSM) advised that olanzapine and risperidone should not be used for the treatment of behavioural symptoms of dementia; there was clear evidence of an increased risk of stroke in elderly patients with dementia, and the risk was considered sufficient to outweigh likely benefits. The CSM also advised that if risperidone was used for the management of acute psychotic conditions in elderly patients with dementia this should be short-term and under specialist advice. Those patients already being treated with an atypical drug were recommended to have their treatment reviewed. [see MHRA advice]

A review by the European Pharmacovigilance Working Party found that the risk of cerebrovascular events associated with other antipsychotics was not significantly different from that of olanzapine and risperidone, and they advised inclusion of a warning about a possible risk of these events in the SPCs for all typical and atypical antipsychotics.

These concerns were reflected in the NICE-SCIE guideline for dementia and are reviewed in the MeReC Bulletin.

What does this study claim?
The authors claim that serious adverse events, as indicated by a hospital admission or death, are frequent following the short-term use of antipsychotic drugs in older adults with dementia, whether atypical or typical antipsychotics are chosen. Serious adverse events appear more common among those who receive a prescription for a conventional antipsychotic drug relative to those who receive a prescription for a newer atypical drug.

What are the limitations?
This was a Canadian cohort study conducted between 1997 and 2004, and may not reflect current practice in the UK. The interpretation that conventional antipsychotics produce more serious adverse events than atypical antipsychotics is uncertain, as the 95% confidence intervals (CIs) of the odds ratios (compared with no antipsychotic treatment) overlap. Although adjustment was made for many patient factors, the possibility that patients who were prescribed typical antipsychotics were more susceptible to side effects can not be ruled out. The authors point out that the study is likely to have underestimated the prevalence of adverse events associated with antipsychotic therapy as it only considered serious adverse events that resulted in acute hospital treatment. There may well have been other side effects that seriously affected the quality of life of patients with dementia that were not reflected in the study findings. It did not take into account adverse events that might have developed after the 30-day follow-up period.

So what?
This review supports the view that all antipsychotics, regardless of their type are associated with an increased risk of serious adverse reactions, even when used over the short-term. It supports the view that they should only be used in exceptional circumstances in people with dementia, only by specialists, and after full discussion about the risks and benefits with the patient and the people who care for them.

You can find further information on the treatment of dementia on the CNS and mental health floor of NPCi

Study details
This was a population-based, retrospective cohort study in which the effects of antipsychotic drug use was compared in 20 682 matched older adults with dementia living in the community and 20 559 matched individuals living in a nursing home. A conditional logistic regression model was used to estimate the odds of suffering a serious adverse event (a composite outcome defined as an event serious enough to lead to an acute care hospital admission or death) within 30 days of initiating antipsychotic therapy.

The most frequently prescribed atypical antipsychotic drug at cohort entry was risperidone (72% community group, 73% nursing home group) and most frequently prescribed conventional antipsychotic drugs was haloperidol (community group 59%, nursing home group 53%)

In the community group, any serious adverse event occurred in 16.0% of those receiving conventional antipsychotics, 13.9% of those receiving atypical antipsychotics and 4.4% of those who received no antipsychotics. In the nursing group the incidences were 11.6%, 9.4% and 5.6%, respectively. Deaths occurred in 4.6%, 2.7%, and 1.2%, respectively in the community group and 6.5%, 5.2%, and 3.3%, respectively, in the nursing home group.

For the community group, those newly dispensed an atypical antipsychotic were 3.2 times more likely (95%CI 2.8 to 3.7) and those who received conventional antipsychotic therapy were 3.8 times more likely (95%CI 3.3 to 4.4) to develop any serious event during the 30 days of follow-up, compared to those who received no antipsychotics.

For the nursing home group, those newly dispensed an atypical antipsychotic were 1.9 times more likely (95%CI 1.7 to 2.2) and those who received conventional antipsychotic therapy were 2.4 times more likely (95%CI 2.1 to 2.7) to develop any serious event during the 30 days of follow-up, compared to those who received no antipsychotics.

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