Efforts to curb the routine use of antipsychotics as a behavioural management tool in the elderly have been further bolstered by the publication of study results suggesting that antipsychotic treatment of people with dementia nearly doubled the risk of death over a three-year period.

Data from previous 12-week placebo-controlled trials had raised concerns about increased mortality in Alzheimer’s disease patients prescribed antipsychotics. However, this was the first long-term follow-up study to demonstrate such an association, noted an editorial in The Lancet Neurology, where the results were published. The findings “highlight the urgent need to review current practices and promote alternative approaches to care for people with dementia”, it added.

In the study funded by the Alzheimer’s Research Trust and led by Dr Clive Ballard of the Wolfson Centre for Age-Related Diseases at King’s College London, 165 patients with Alzheimer’s disease (aged 67 to 100 years) at care homes in the UK were randomised to either continue their antipsychotic treatment (thioridazine, chlorpromazine, haloperidol, trifluoperazine or risperidone) for 12 months or switch to placebo.

A total of 83 patients were randomised to continue with antispsychotics and 82 to placebo, of whom 128 (78%) started treatment (64 continuing with antispsychotics, 64 to placebo). The primary outcome was mortality at 12 months and there was an additional follow-up assessment by telephone to establish whether participants were still alive 24 months after the enrolment of the last patient, with a range of 24-54 months. The study was conducted between October 2001 and December 2004.

The researchers found that the cumulative probability of survival over the 12-month period was 70% in the group that continued antipsychotic treatment and 77% in the placebo group. This discrepancy widened to a 46% survival rate for antipsychotic versus 71% for placebo patients at 24 months and to 30% and 59% respectively at 36 months.

As the Alzheimer’s Research Trust pointed out, as many as 100,000 people with dementia are routinely prescribed antipsychotics in UK care homes. The drugs are used to treat symptoms of agitation, delusions and aggressive behaviour. NICE guidelines recommend using antipsychotics only for short periods of time where symptoms are severe, and with very careful monitoring. In clinical practice, though, the average length of an antipsychotic prescription is one to two years, the Trust noted.

Wake-up call

Rebecca Wood, chief executive of the Alzheimer’s Research Trust, called the study findings “a real wake-up call” that underlined “the danger of prescribing antipsychotics long-term for anything other than exceptional circumstances”. According to Dr Ballard, there is “still a limited place for antipsychotics in the treatment of Alzheimer’s, particularly severe aggression, but the serious concerns of the drugs shown by our research emphasise the urgent need to put an end to unnecessary and prolonged prescribing”.

The UK government is conducting a review of antipsychotic use in dementia and will address the issue in its pending National Dementia Strategy. Neil Hunt, chief executive of the Alzheimer’s Society, said the Strategy “must seize the opportunity and ensure antipsychotics are always a last resort”. Alzheimer’s Society research showed that specialist dementia training for care staff could reduce antipsychotic use by 50%, he noted.

Inadequate staff numbers and lack of appropriate training in dealing with the sometimes “extremely challenging” behavioural and psychological symptoms of dementia mean antipsychotics “are used unnecessarily as a first option in many instances”, the Lancet Neurology editorial commented.

“More studies, including randomised controlled trials, to test the efficacy of psychosocial alternatives might help to convince policymakers to invest in improved training of multidisciplinary teams that should include specialist dementia nurses,” it suggested. “Greater involvement of families in care decisions and frequent monitoring and review of care plans would also help to ensure that treatment is tailored to individual patients.”