Alzheimer's drug fails to reduce significant agitation

A drug prescribed for Alzheimer’s disease does not ease clinically significant agitation in patients with Alzheimer’s disease, according to a new study led by the University of East Anglia (UEA).

Published today by US journal PLoS ONE, the findings, while confirming that the drug Memantine improves cognitive functions of the brain such as memory, suggest that it is no more effective at reducing significant agitation than placebo.

More than 450,000 people in the UK suffer from the form of dementia known as Alzheimer’s disease. Many are agitated and, for example, pace continually, become physically or verbally agressive, or scream persistently. As well as harming quality of life for the patient, agitation places enormous strain on relationships with family and carers, and often results in institutionalisation.

“Feelings of agitation are an enormous problem in Alzheimer’s dementia , creating a costly and distressing burden both for patients and those who care for them,” said Dr Chris Fox of Norwich Medical School at UEA, who led the research.

Memantine is licensed for use in many countries including the UK, the US and in Europe. Previous restrospective studies have suggested it could help with reducing agitation, and it is one of a number of Alzheimer’s treatments recommended by the UK’s National Institute for Clinical Excellence (NICE).

Dr Fox said: “People who have mild symptoms often respond to changes in the environment or psychological treatment, but these methods are impractical in severe agitation. Our findings regarding Memantine are disappointing with respect to severe agitation - particularly as the alternative antipsychotic medications can have significant side effects such as increased rates of stroke and death. However, we hope our study will highlight the urgent need for investment in safe and effective new treatments for this growing disease,” said Dr Fox.

Funded by Memantine manufacturers Lundbeck, the study is the first randomised controlled trial designed to assess the effectiveness of the drug for significant agitation in Alzheimer’s patients.

Dr Fox worked with colleagues at the Indiana University, University College London, University of Kent, Aston University, Oxleas NHS Foundation Trust, and Kings College London.

The team of researchers studied 153 nursing home residents and hospital inpatients with severe Alzheimer’s from September 2007 to May 2010. All the participants were suffering from significant agitation requiring clinical treatment. Half were given Memantine and half were given a placebo. The results showed signficant improvement in cognitive function and for overall neuropsychiatric symptoms for the group given Memantine, but no statistically significiant difference in terms of the severe agitation that was the primary focus of the study.

“Agitation in Alzheimer’s Disease is particularly difficult for family carers to deal with and is associated with so-called ‘carer collapse’. We now need further research on innovative ways involving both pharmacological and non-pharmacological treatments to effectively manage this very distressing complication of Alzheimer’s Disease,” said Ian Maidment of the pharmacy department, Aston University.

Prof Gill Livingston, of University College London, added: “The impact of agitation can be devastating. For the person with dementia, the agitated feelings and behaviour often occur several times per hour, occupying a considerable proportion of their day. It affects relationships within the family and is often associated with feelings of helplessness, anxiety, and anger among family, paid carers and others. The only drugs which we know work have severe side effects and it is therefore very disappointing that this drug did not work in these severely agitated patients and means we should quickly investigate other possible treatments.”

Anne Corbett, research manager at the Alzheimer’s Society, said: “This research suggests that even though Memantine can have real benefits for people in the later stages of Alzheimer’s, it may not have all the answers. However, prescribers should not see the only alternative as being to hand out antipsychotics. These overprescribed drugs, double the risk of death and treble the risk of stroke and should always be a last resort for people with dementia.

“There are often underlying causes to symptoms such as agitation and it is imperative care staff are empowered with training to identify and treat them. Medications might form part of this picture but they must not be a replacement for good quality care.”

In response to the study, Lundbeck commented: “We agree with the study authors that further trials are needed to address suitable alternatives to antipsychotic medications for these patients. As the current study reports negative results for severe agitation but positive results for overall neuropsychiatric symptoms, further assessments of longer duration are needed.”

‘Efficacy of Memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial’ by C Fox (UEA), M Crugel (Oxleas NHS Foundation Trust), S Coulton (University of Kent), I Maidment (Aston University), BH Auestad (University of Stavanger, Norway), A Treloar (Oxleas NHS Foundation Trust), C Ballard (Kings College London), M Boustani (Indiana University and the.Regenstrief Institute, USA), C Katona (University College London), and G Livingston (University College London) is published by PLoS ONE on Wednesday May 2 2012.

The trial was sponsored by East Kent Hospitals University NHS Foundation Trust.

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