Healthy Skepticism Library item: 9294

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Publication type: media release

Shocking new research: Alzheimer's patients are dying early because of controversial drugs
Alzheimer's Research Trust 2007 Mar 30
http://www.alzheimers-research.org.uk/news/article.php?type=News&id=99

Full text:

Many Alzheimer’s patients are dying earlier because of sedatives they are being prescribed, according to new groundbreaking research from the Alzheimer’s Research Trust.

Results from a five-year project, funded by the Alzheimer’s Research Trust and presented at the charity’s conference in Edinburgh, found that the drugs were linked with a significant increase in long-term mortality – with patients dying on average six months earlier.

The investigation by King’s College London researchers found that the sedatives, known as neuroleptics, were associated with a significant deterioration in verbal fluency and cognitive function, and that neuroleptic treatment had no benefit to patients with the mildest symptoms.

Significantly, up to 45% of people with Alzheimer’s disease residing in nursing homes are prescribed neuroleptics as a treatment for behavioural symptoms such as aggression.

Professor Clive Ballard, Professor of Age Related Disorders at King’s College London, and lead researcher on the project, said:

“It is very clear that even over a six month period of treatment, there is no benefit of neuroleptics in treating the behaviour in people with Alzheimer’s disease when the symptoms are mild – specifically when a measure of behavioural disturbance known as the Neuropsychiatric Inventory Score is equal to or less than 14. For people with more severe behavioural symptoms, balancing the potential benefits against increased mortality and other adverse events is more difficult, but this study provides an important evidence base to inform this decision-making process.”

Rebecca Wood, Chief Executive of the Alzheimer’s Research Trust, said:

“These results are deeply troubling and highlight the urgent need to develop better treatments. 700,000 people are affected by dementia in the UK, a figure that will double in the next 30 years. The Government needs to make Alzheimer’s research funding a priority.

“Only £11 is spent on UK research into Alzheimer’s for every person affected by the disease, compared to £289 for cancer patients.”

Janet Carter, from West Yorkshire, whose parents were both diagnosed with Alzheimer’s, said: “My father died relatively quickly after he was diagnosed with Alzheimer’s and he was prescribed a neuroleptic drug. My mother, who also has Alzheimer’s, is still alive almost a decade after being diagnosed. She was never given these drugs. I don’t know if what happened to my dad is linked to these findings, but either way I’m very shocked by them.”

This is the largest neuroleptic withdrawal study of Alzheimer’s patients and the only long-term one of its type.

Further information:

About the research
• The grant “Neuroleptics: do they accelerate cognitive decline and exacerbate neuronal loss?” was funded by the Alzheimer’s Research Trust. It began in July 2001 and ran until June 2006
• 165 participants with Alzheimer’s disease living in nursing homes in Oxfordshire, Newcastle, Edinburgh and London, who had been taking neuroleptic drugs for at least 3 months, took part in a long-term randomized double-blind placebo controlled neuroleptic withdrawal trial
• The neuroleptics in the study were thioridazine (Melleril), chlorpromazine (Largactil), haloperidol (Serenace), trifluoperazine (Stelazine) and risperidone (Risperdal). Patients continued to take their prescribed neuroleptic drug for 12 months or took a matched placebo
• Additional follow up was completed a minimum of 12 months after initial enrolement (range 24-54 months) to determine the impact of continuing or discontinuing neuroleptics on mortality. The differences in survival were particularly striking at 24 months (78% v 55%), 36 months (62% v 35%) and 42 months (60% v 25%)
• These findings were presented at the Alzheimer’s Research Trust Network Conference, which took place at the Royal College of Physicians in Edinburgh on Wednesday 28th and Thursday 29th March 2007. It was attended by 160 medical experts and scientists from universities across the UK linked by the Alzheimer’s Research Trust Network

About the Alzheimer’s Research Trust
• The Alzheimer’s Research Trust is the UK’s leading research charity for Alzheimer’s disease and related dementias, and is dedicated to funding and encouraging the very best UK-led research
• The Alzheimer’s Research Trust relies solely on donations to fund its research

About neuroleptics
• Neuroleptics are sedative drugs, also known as major tranquilisers or anti-psychotics. They are not licensed for the treatment of dementia, but are prescribed to some people with dementia to control agitation, delusions, anxiety, hallucinations, sleep disturbance, and aggressive behaviour
• Originally used to treat schizophrenia, neuroleptics are prescribed to up to 45% of people with Alzheimer’s living in residential or nursing homes (Reference: McGrath AM, Jackson GA. Survey of prescribing in residents of nursing homes in Glasgow. BMJ 1996;314:611-2)
• An ongoing study funded by the Alzheimer’s Research Trust is investigating the mechanisms by which neuroleptics may accelerate Alzheimer’s pathology in the hope this will improve our understanding of how the disease progresses and lead to new treatments

About anti-Alzheimer’s drugs
• There are three drugs licensed for the treatment of mild to moderate Alzheimer’s disease, known as cholinesterase inhibitors: donepezil (Aricept), galantamine (Reminyl), rivastigmine (Exelon). In November 2006, despite evidence of benefits to patients, the National Instititute for Health and Clinical Excellence (NICE) recommended the restriction of these drugs to only those in the moderate stages of the disease
• A fourth drug, Memantine (Ebixa), is the first licensed for the moderately-severe to severe stages of Alzheimer’s. Again, despite evidence of benefits to some patients, it is not recommended by NICE for prescription on the NHS except for as part of clinical research trials.

Alzheimer’s Research Trust position on neuroleptic treatment following release of these results:

Cummulative evidence now suggests that neuroleptics should be reviewed and discontinued in Alzheimer’s patients with a Neuropsychiatric Inventory score of less than or equal to 14, given the potential adverse events of ongoing neuroleptic treatment. In other words dementia patients on long-term neuroleptic treatment with mild behaviour problems would generally be better off having the drug withdrawn.

The situation is more complex for those experiencing severe behavioural symptoms which can be distressing both for the patient and carer and sometimes dangerous. If continuing treatment, this should be monitored carefully and the modest benefits weighed against the potential incredibly serious side-effects shown by this study.

This data further adds to the serious safety concerns with long-term use we encourage clinicians to try to replace neuroleptics with safer management approaches. Many studies have demonstrated that psychological management approaches can replace neuroleptic therapy without significant worsening of behavioural symptoms. Evidence is emerging that cholinesterase inhibitors or memantine may be safer and effective alternatives for some symptoms.

This new study will feed into a Cochrane review later in 2007 of the use of neuroleptics in Alzheimer’s disease – this will summarise all known evidence and help provide solid guidance for clinicians.

For now we suggest these drugs should only continue to be prescribed long-term to dementia patients experiencing severe behavioural problems and only as a last resort when non-drug methods have been tried and failed.