[e-drug] Neuroleptics - dangerous in Alzheimer's?

["E-Drug" <e-drug@healthnet.org>]

E-DRUG: Neuroleptics - dangerous in Alzheimer's?
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[A worrying story from UK where Alzheimer patients are being put on
neuroleptics to control agitation, hallucinations and erratic behaviour [to
cover up for shortages of nursing staff?], despite only being licensed for
use in people suffering from schizophrenia. The increase in mortality is
worrying. Olanzapine and risperidone were already contraindicated in
Alzheimer due an increased risk of stroke and death. Crossposted from
DRUGINFO with thanks. Copied as fair use. WB]

http://society.guardian.co.uk/health/story/0,,2046457,00.html 

Alzheimer's sufferers dying in drug 'scandal'
· Sedatives blamed for thousands of deaths
· Campaigners point to lack of cash for trained staff 
Polly Curtis, health correspondent
Friday March 30, 2007
The Guardian 

A class of drugs widely prescribed for people suffering from dementia is
leading to the premature deaths of thousands of patients every year,
according to research published today. Campaigners branded the continued use
of the sedatives, called neuroleptics, a national scandal after a five-year
study revealed that people with Alzheimer's disease and other forms of
dementia are twice as likely to die if they are prescribed them.
Neuroleptics are widely prescribed to help control symptoms of Alzheimer's
and dementia including agitation, hallucinations and erratic behaviour,
despite only being licensed for use in people suffering from schizophrenia.
The research suggests they are of little benefit to patients with milder
symptoms, greatly increase their risk of dying prematurely, and that 45% of
Alzheimer's patients in care homes are prescribed a neuroleptic drug.

A group of 165 Alzheimer's patients were randomly assigned to take one of
three types of neuroleptic drugs, or a placebo. After two years 45% of those
who took the real drugs had died compared with 22% who were given the
placebo.

The King's College London researchers who undertook the project, funded by
the Alzheimer's Research Trust, found that after three years 65% of those on
the drugs had died compared with 38% of those on placebos. After 42 months
75% of those on the drugs had died compared with 60% on the placebo. On
average patients who were on the drugs died six months earlier.

Clive Ballard, professor of age-related disorders at King's and the lead
researcher, said that not only were people more likely to die but they also
suffered severe side-effects including stroke, chest infections and falls.

"If this was a massive increase in mortality in children there would be an
outcry. Older people aren't seen as a priority. These sedatives are being
used because the services can't cope with people who are in a distressed
state. There are ways to avoid them but it would involve training of staff,
which is costly."

In 2004 the medicines watchdog issued a warning that two types of
neuroleptics, olanzapine and risperidone, should not be given to Alzheimer's
patients because of an increased risk of stroke and death.

Despite this, in 2005 the Alzheimer's Society presented evidence that
100,000 people suffering from dementia were being prescribed a neuroleptic
drug.

Neil Hunt, chief executive of the society, said: "Neuroleptics have been
used as a dangerous fix for 'challenging behaviour' in people with dementia
for too long. They are not licensed for use among people with dementia, but
continue to be hugely over-prescribed. It is a national scandal that people
are being sedated in this way ... These drugs must be a last resort, only
used when all other methods have failed to alleviate the most distressing
symptoms of dementia."

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."

The Medicines and Healthcare products Regulatory Agency (MHRA), which is
responsible for the safety of medications, said neuroleptics were not
licensed for use to treat dementia. "The MHRA continues to monitor the
unlicensed use of neuroleptics in the treatment of patients with Alzheimer's
disease and will carefully review this new study to see what further action
may be necessary."

Professor Mayur Lakhani, chairman of the Royal College of General
Practitioners, said: "We would like to reassure patients, relatives and
carers that neuroleptic drugs are not routinely prescribed to patients with
dementia, and are used only as a last resort when patients suffer from
severe episodes."

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