While our Deputy Editor, John O’Brien, was preparing the December 2000,
and March 2001 issues of IPA Bulletin and I was concentrating on the Lorne Regional Meeting which took place in February, 2001, he had the
bright idea of asking our assistant editors to indicate whether anti-dementia drugs were available and/or subsidized in their countries. My interest in
this area is long-standing and was aroused even further when I found that an Australian patient of Turkish origin, whom I had been treating for some
time, was obtaining subsidized donepezil from a relative in Ankara. The relative,
despite not having Alzheimer’s disease (AD), was eligible for the subsidized drug as he was in receipt of a Turkish government pension at a
time when the Australian government was not subsidizing cognitive enhancing drugs for anyone! Here then is the response from our assistant
editors around the globe. All assistant editors were asked for a contribution and this piece includes all responses received by 8 October 2001. Any
further information on the state of affairs in countries not mentioned below will be gratefully received and edited to appear in the next available issue
of IPA Bulletin. —DAVID AMES, EDITOR
In Australia the approval process for new drugs has two stages. The
Therapeutic Goods Administration determines whether a product can be
marketed. Subsequently, the Pharmaceutical Benefits Advisory
Committee recommends to the Health Insurance Commission whether
there is enough evidence to justify subsidy of the drug on the national
Prescriber Benefits Scheme (PBS) which makes medications available
for a nominal charge equivalent to less than $US2 to pensioners and
$US12 to the rest of the population. Several drugs are marketed without
being approved for reimbursement on the PBS, but as these drugs are
expensive availability is limited to those wealthy enough to afford them.
Tacrine (Cognex) was approved for marketing in Australia by the TGA
in 1995, but two successive applications for a PBS listing were refused.
Donepezil (Aricept) was approved for marketing in 1998, but an initial
application for PBS listing was turned down, ostensibly for cost/benefit
reasons. Rivastigamine (Exelon) was approved for marketing in 2000
and both it and donepezil became available on the PBS from February
2001, after subsequent applications with additional evidence by Pfizer
and Novartis respectively. Galantamine (Reminyl) was approved for
marketing and PBS subsidy from 1st November 2001. The rules for prescribing
subsidized anti-dementia drugs are complex. Patients must
have a diagnosis of probable mild to moderate AD confirmed by a psychiatrist
or physician. They must show a two-point improvement on the
Mini Mental State Examination (MMSE) scale within six months of
commencing treatment to continue to receive subsidized drug after six
months have passed. For patients with high MMSE scores (who cannot
increase their MMSE scores very much by definition), an alternative
provision is to show a four-point improvement on the ADAS-Cog scale.
PBS authority clerks refuse applications to use cholinesterase inhibitors
in patients whose MMSE scores are below
10, which discriminates against those
with limited education and those who do
not speak English. —David Ames
(dames@unimelb.edu.au)
Three cholinesterase inhibitors are officially
marketed in Brazil: tacrine, rivastigmine
and donepezil. Tacrine has been
available since 1994 under the trade names Tacrinal and Cognex, the latter
being cancelled in September 2000. Rivastigmine (Exelon) has been
available since 1998 and donepezil (Eranz) since late 2000, although its
initial application was in 1998. Galantamine is expected to be marketed
within a few months, but it can be prescribed and acquired through
importation already. Rivastigamine is the most prescribed of these drugs.
The overall prescription numbers are much below the candidate population,
considering there are 15 million individuals over the age of 60.
The high cost of cholinesterase inhibitors is perhaps the main limitation
upon wider use. The monthly costs in therapeutic doses range from
$US70-100 for rivastigmine and donepezil, and $US180-230 for galantamine,
making such treatment inaccessible for more than 85% of elderly
Brazilians. Efforts to warrant the medication for those economically disadvantaged
are in progress within governmental institutions. In Brazil,
special medications that are not provided at the primary care level (usually
the most expensive drugs) can be obtained upon documented
request from a physician. By this mechanism patients can receive special
medications free at hospitals or academic institutions, which are further
reimbursed for costs. The current list of special medications does not
include cholinesterase inhibitors so far, but the inclusion of rivastigmine
is under negotiation between governmental, pharmaceutical, and academic
representatives. The Brazilian branch of Alzheimer’s Disease
International (ABRAZ) is actively dealing with this issue. —Orestes V.
Forlenza (forlenza@NETPOINT.com.br)
Donepezil and rivastigmine are approved for treatment of AD. In Canada
donepezil has been available for several years. Rivastigmine has come
out more recently. Approval is by a national body called the Health
Protection Branch of the Federal Government (roughly equivalent to the
FDA in the US). Many drugs are paid for seniors by provincial insurance
plans. However in the case of cognitive enhancers some jurisdictions
require that the drug has shown clinical effectiveness for a given patient
before the provincial plan will pay for the treatment. —Joel Sadavoy
(j.sadavoy@utoronto.ca)
In Croatia, donepezil and rivastigmine are approved for use in dementia of
the Alzheimer type. But, unfortunately, the full price must be paid for both
medications, although donepezil was free of charge when prescribed by a
neurologist between September 1998 and September 2000. After recent
restrictions concerning the government list of medications, donepezil must
now be paid for in full. Tacrine has never been approved in Croatia.
Galantamine probably entered the country in a trial but has not been
approved yet. —Danilo Hodoba (vrapce02@mail.bolnica-vrapce.hr)
In Denmark the antidementia drugs are restricted. The drugs can only be
prescribed by specialists in psychiatry, neurology and geriatrics and only to
patients with AD in the mild and moderate stage. Tacrine has only been
used in drug trials. The drug was not marketed in Denmark. From 1997 the
first drug that became available was donepezil. The price of the drug could
be reimbursed after application to health authorities. Rivastigmine was
marketed in 1998 but with less apparent success than donepezil. The
Danish office is closed now. Galantamine has been used since October 2000.
The costs of these drugs are partly reimbursed after application to the
health authorities with information of disease, stage, blood samples and CT
brain scan. This became obligatory long before all areas had the capacity to
do a CT scan without a substantial waiting time. CT scans are still a problem
for patients who cannot co-operate with the investigation.
—Kirsten Abelskov (psykiatri.risskov.ka@aaa.dk)
In Hong Kong, Tacrine was used for two to three years when it was first
launched, but is no longer used. Instead two cholinesterase inhibitors are
commonly used. Donepezil was launched in June 1998 and was approved
by the Drug Advisory Committee (DAC) of the Hospital Authority a month
later. Rivastigmine was launched in April 1999 and was approved by the
DAC in July 2000.
The Health and Welfare Bureau of Hong Kong has recently outlined policy
initiatives to allocate additional resources to supply new psychiatric drugs
(atypical antipsychotics, new antidepressants, new antidementia drugs) to
improve the quality of life of the mentally ill. There is a small budget for
antidementia drugs this year. Local clinical guidelines for the use of
cholinesterase inhibitors have been developed, with the aim to promote
rational prescribing under finite and limited funding resources.
Suitable patients for prescription are those suffering from mild to moderate
AD, or in some cases, Dementia with Lewy Bodies with behavioral and psychological
symptoms of dementia. They are preferably community dwelling
with a reliable caregiver to ensure compliance. There should be no medical
contraindication. Continuous clinical monitoring is emphasized once a
patient has been put on the drug, with review at 2 to 4 weeks for any possible
side effects and/or to titrate the dose. After patients have been on a maximum
tolerable dosage for 12 weeks, they are evaluated for clinical response
such as improvements in cognitive functions, activities of daily living, emotional
or behavioral problems or global assessment. Patients who clearly
benefit from treatment should continue. If treatment is continued, a
review is conducted every 3 to 6 months. Decisions to stop treatment are
difficult. In general, discontinuation is considered if there is lack of
clinical response; the patient has entered the severe stage of dementia;
or if there is poor compliance or upon the emergence of medical contraindications.
During the resource allocation process, several factors were taken into
consideration for cholinesterase inhibitors: the number of mild to moderate
dementia cases in society; the significant distress and disability
caused by dementia to both patients and their carers; the evaluated
effectiveness of the new antidementia drugs in relation to the cost; the
absence of effective alternative drug-treatments; and the foreseeable possibility
of increasing demands from the public as they begin to realize
the existence of such new drugs for their demented relatives. So far the
resources are far from adequate. Less than one-third of those new
patients in the coming year who fulfill the criteria to receive
cholinesterase inhibitors would be given the drugs because of limited
resources. —T K Poon (yuenlingwong@cuhk.edu.hk) and Helen Chiu
(helenchiu@cuhk.edu.hk)
Donepezil,
rivastigmine, and galantamine are all available in Ireland.
Individuals who hold a medical card can get these without charge and
there are no restrictions with regard to dementia severity. Anyone without
a medical card gets reimbursed for medication costs that are greater
than £IR42 per month. In our last budget the government made provision
for all individuals over the age of 70 to have a medical card regardless
of income. All three of these drugs may be prescribed by general
practitioners (GPs) without prior referral to a specialist. However, many
do refer to neurologists, old age psychiatrists or geriatricians to confirm
the diagnosis of probable AD. —Greg Swanwick (swanwick@iol.ie)
In Israel, donepezil (Aricept, Memorit and Asenta), rivastigmine
(Exelon) and tacrine (Cognex), have been approved for the treatment of
the early stages of AD, since January of 2000. It is expected that galantamine
will be approved shortly. The first stage in the approval process was
to present the product and its benefits, supported by references and
pharmaceutical advisory, to the Ministry of Health, Health Technology
and Infrastructure Administration—Division of Medical Technology
Policy. In Israel there are approximately 60,000 patients with AD and we
expect this number to double by the year 2020. The clinical guidelines
in Israel for the cholinesterase inhibitors and the rules for prescribing
subsidized anti-dementia drugs are complex. Our National Health
System determined a basket of drugs for various diseases. In addition we
have various health insurances with additional regulations and restrictions:
1) patients must have a diagnosis of probable AD according to
NINDS-ADRDA, or DSM-IV 290.10/290.0; 2) severity should be at mild or
moderate level, at most; 3) CDR should not exceed level 1 or 2; and 4)
the MMSE score has to be between 10 and 26.
The patients should have no medical contraindication or concomitant
severe neurological illness associated with cognitive decline (no past
history of vascular dementia.), chronic illnesses (severe diabetes or heart
block), and addictions to alcohol or drugs. They should be preferably
community dwelling with a reliable caregiver to ensure compliance.
The drugs have to be prescribed only by an MD specializing in geriatric
psychiatry, psychiatry, neurology or geriatrics. The MD must be a senior
or a director of a memory clinic, Alzheimer’s clinic, neurobehavioral
unit and cognitive assessment clinic, or director of an outpatient clinic.
The drug should be discontinued in case of severe side effects. The
patient should be followed for at least six months and if observation
shows a decrease in CDR or/and decrease in total MMSE score over three
points or four points on the ADAS-Cog, the drug should be withdrawn.
The Alzheimer Association of Israel is strongly involved in promoting
the need for pharmacotherapy and has a strong and fruitful relationship
with the medical system. —Simona Naor (naoranms@netvision.net.il)
Donepezil is the only drug for AD approved by the Japanese Government.
Governmental approval was based mainly on the report of a doubleblind
placebo controlled, multi-center trial in Japan in 1999. In that
study, the efficacy and safety of donepezil were proven at 5mg/day in
patients with mild to moderately severe AD over 24 weeks of treatment.
Tacrine is not available in Japan. Other selective acetylcholinesterase
inhibitors, rivastigmine, galantamine, metrifonate, amiridin,
benazepine, and cholinergic receptor agonists, quinuclidine, azaspirodekan
and chenopyrimidine, are now on clinical trials. Some of
these drugs are expected to be approved by the Government for the treatment
of AD.
Vitamin E, selegiline and NSAIDs are available in Japan, although these
drugs are not approved as anti-dementia drugs. Nerve Growth Factors
are not available for clinical use. Amantadine hydrochloride, aniracetam,
nefiracetam, nicergoline, nilvadipine, vinpocetine, cinepazide
maleate and ibudilast are used for the management of non-cognitive
symptoms in vascular dementia.
Idebenone and indeloxazine were commonly used in Japan to treat
memory impairment or emotional disturbance in patients with cerebrovascular
disorders. Placebo-controlled clinical re-trials of these drugs
were performed at the request of the Government. In 1998, the trials
proved these drugs had no significant effect on the cognitive and affective
symptoms of cerebrovascular disorders. Since then, the Government
stopped the use of these drugs in Japan. —Koho Miyoshi (miyoshi@hiabcd.go.jp)
In Mexico, only donezepil and rivastigmine are approved for use in
dementia of the Alzheimer type. Both drugs are available in pharmacies
for anyone who can afford them and would like to buy them with or
without a prescription. Both antidementia drugs are extremely expensive.
The drug companies set prices, but before reaching the public the
prices increase from 20 to 40 percent. The drug companies sell the drug
to a distributor, which in turn resells medication to the chemist. In this
chain, prices become unsustainable for most novel drugs. Prescription
of these substances is not regulated. Any physician who has finished
medical school, without any further training, is entitled to prescribe any
drug with the exception of narcotic analgesics. Our national health system
has a basket of drugs used for the treatment of up to 60 percent of
the Mexican population. In this basket, only medications that are no
longer held on a trademark are distributed free or at very low prices.
Under these conditions, those patients who might benefit from antidementia
drugs have to seek treatment outside the governmental health
system and sacrifice a big part of the family income to buy these medications.
—David Resnikoff (resnikoff@hotmail.com)
In the Netherlands only rivastigmine is available. It is the first
cholinesterase inhibitor on the Dutch market. Tacrine was never registered.
Rivastigmine is included in the “Geneesmiddelen
Vergoedingssysteem” (GVS) that can be translated as Drugs
Reimbursement System, but with some restrictions. The restrictions are:
mild to moderate AD (MMSE between 10 and 26); prescribed by a medical
specialist, specializing in the care of patients with dementia; and
advance approval of the Health Insurance Fund.
In our practice, not many patients or their relatives ask for rivastigmine.
Following one or two very positive reviews in the newspapers shortly
after registration, most articles now in the media give a more balanced
view of the positive and negative effects of rivastigmine. A positive effect
of the discussion about how to decide whether these drugs work is in the
development by the Health Fund Council. This will be in the form of
guidelines promoting the use of rating scales or other instruments during
the treatment of patients with dementia (whether with or without
anti-dementia drugs). —Thea Heeren (t.heeren@altrecht.nl)
In New Zealand rivistigmine and donepezil are both registered and
available for the treatment of AD. However neither are currently subsidized.
Pharmac, the body which determines subsidies for medications
for the New Zealand public health system, is currently considering the
issue of subsidizing anti dementia drugs. —Anthony Duncan
(anthony_duncan@moh.govt.nz)
Cholinesterase inhibitors are not available in Nigeria. Many reasons
account for this. First, only about 3% of the population are aged 65 years
and over, while children under 15 years constitute 48% of the population,
so the thrust of health care is towards prevention of infective conditions in
children and young adults. Second, dementia research is limited and the
major studies published confirm that both prevalence and incidence rates
of dementia and AD are relatively low here. Third, there is no national
health insurance (although one is being proposed), so patients have to
pay for treatment in hospitals. Pharmaceutical companies marketing the
popular cholinesterase inhibitors are represented in Nigeria, but there is
reluctance on their part to market these drugs because of the projection of
possible poor sales, especially as these drugs are very expensive and are
required by the most impoverished segment of the society, the elderly.
Many older persons receive no pension or other forms of public assistance
and depend entirely on the financial support of their families.
Before drugs are marketed in Nigeria approval must be obtained from
the National Agency for Drug Administration and Control (NAFDAC).
This usually follows clinical trials.
Since cholinesterase inhibitors are unavailable for general prescription,
doctors are limited to the use of apha-tocopherol (vitamin E), apart
from treating the behavior disorders that may accompany dementia
with antidepressants and neuroleptics. However, psychiatrists and neurologists
in some university teaching hospitals prescribe donepezil to
patients who are able to buy the drug from abroad. Usually, these are
doctors interested in dementia research and treatment. It is hoped that
the situation will change in the near future. —Olusegun Baiyewu
(baiyewuo@infoweb.abs.net)
In Norway donepezil was the first acetyl cholinesterase inhibitor on the
market. Tacrine was never approved for marketing. Donepezil was
approved in 1999, rivastigmine in 2000 and galantamine at the beginning
of 2001. The rules for prescribing the acetyl cholinesterase
inhibitor are complex. Patients must have a diagnosis of AD of mild to
moderate degree. Only specialists in psychiatry, neurology and internal
medicine are allowed to prescribe the drugs. They should also follow the
patient up for six months and decide whether it is useful or not.
Thereafter the patient could be followed up by a GP. So far, application
for total reimbursement through the National Health Insurance has
been turned down for cost/benefit reasons. The National Health
Insurance reimburses less 65% of the total costs of the treatment. In
other words the patients have to pay about $US400 per annum.
—Knut Engedal (knut.engedal@mail.powertech.no)
In Singapore, before any drug is introduced to the public, the pharmaceutical
company has to submit reports on its efficacy and side effects to
the Ministry of Health’s drug regulatory committee. It is the usual practice
for most pharmaceutical companies to submit an approval letter
from the US FDA or the European equivalent, before submission to the
Ministry of Health. For psychotropic medication, the Ministry of Health’s
Chief of Pharmacy will send the reports to the Chief of Psychiatry in the
University or the main public mental hospital. The Ministry of Health
committee will then review the recommendation by the psychiatrist,
before it is licensed for prescription by doctors. The first anti-dementia
drug approved in Singapore was tacrine in 1996; donepezil was
approved in 1998 and rivastigamine in 1999. Currently only the last two
drugs are used—Tacrine has been withdrawn. They can be prescribed by
any doctor and, in Singapore, though most of the prescriptions are from
psychiatrists or neurologists. These two medications are not included in
the standard list of hospital drugs and the government does not subsidize
the prescriptions. —Kua Ee Heok (Pcmkeh@nus.sg)
Slovenia has a national health insurance system very like the British one,
which covers expenses for prevention and treatment of serious illnesses.
The National Health Insurance Company has introduced three lists of
drugs referring to covering the costs: positive, intermediate and negative.
Drugs on the positive list are free to the patient. Drugs on the intermediate
list are free but under the condition that a small contribution to the national
health insurance is paid yearly. Up to 95% of the population is insured in
this way. Without this additional insurance, one must pay a small sum for
the prescription. Full price must be paid for drugs on the negative list.
The intermediate list includes the newer antidementia drugs, donezepil
and rivastigmine. They are on the intermediate list due to their high
price and, perhaps, doubts about their efficacy. Prescribing is no longer
restricted, however, as it was at the very beginning of their registration
and use in 1998. We are expecting galantamine to be approved in
Autumn of 2001. After approval it will first be listed on the negative list,
as is common for any newly registered drug. Tacrine was not approved
for marketing in Slovenia. Some colleagues still prescribe other antidementia
drugs like nimodipine (Nimotop), piracetam and co-dergocrine
(Hydergine). They are all on the positive list, which means they are free.
—Joze Darovec (joze.darovec@guest.arnes.si)
The marketing of the Cholinesterase Inhibitor (CI) drugs in Spain quickly
followed their availability on the international market. Donepezil and
rivastigmine are the most used, though tacrine is still available; galantamine
it is expected to be approved in Autumn of 2001. An achievement of
the welfare system of the Spanish State in recent decades, has been developments
derived from the General Law of Health. This concedes to all
Spanish citizens the same rights to receive all scientific diagnostic and
therapeutic procedures for all kind of illness, virtually free of cost. The
health system rests largely on a public assistance network. When a
physician of the public health system prescribes a drug, the patient accedes
to it under low cost (40% for the general regime; free of charge for pensioners).
This legal situation would permit, in theory, most AD patients to
receive CI drugs free of charge, when their AD is “mild to moderate” as formally
recognized by the government health system.
In recent years, the high cost of a number of new drugs (CIs included)
caused concern to the health authority. For this reason, several cautions
have been taken that apply throughout Spain: 1) CI drugs can only be prescribed
by specialists (psychiatrists, neurologists or geriatricians), who
should: 2) write a clinical report specifying the diagnosis of AD (in a broad
sense); 3)the prescription must be approved, at least the first time, by a
health authority outside the therapeutic team; and 4) the number of prescriptions
for each patient is carefully followed by the health system.
Furthermore, since the Spanish State is configured in Autonomous
Regions, with the capacity to develop specific health legislations, these
restrictions are stressed in the case of Catalonia, where it is required
that: a clinical report, well documenting the severity of the AD type
dementia; an MMSE score higher than 10 is mandatory; said report is
evaluated by an “Advisory Committee on AD”, comprising 3 neurologists,
1 psychiatrist and 1 geriatrician, who every month study all
requests submitted by Catalonian specialists; every case is also reviewed
once per year; any discontinuation of the treatment must also be communicated
to the Committee.
The medical contraindications for initial prescription or for discontinuation
of treatment are at the discretion of the prescriber, with the exception
of Catalonia. When the MMSE score becomes less than 10, the
Committee makes a decision based on the judgement of the prescriber,
and patient/carer opinion on the apparent usefulness of the treatment.
This situation has stimulated a clinical trial to assess the efficacy of
rivastigmine in patients with severe AD, which is currently being carried
out in Spain. —Raimundo Mateos (mrmateos@usc.es) and Manuel
Sánchez-Pérez (manuelanchez@mx2.redestb.es)
Results from epidemiological studies of dementia in Taiwan showed
that the prevalence rate of vascular dementia was higher than that of
dementia of Alzheimer type. Some medications have long been suggested
for dementia due to cerebral blood flow insufficiency, for example,
co-dergocrine mesylate (Hydergin) pentoxyifyline (Trental), and piracetam
(Nootropil). They have been used for a period of time and their
efficacies have not been systemically studied.
In recent years, AD has caught more and more attention, not only of
neurologists or psychiatrists, but also the Department of Health. At the
present moment, medications specifically for the treatment of AD in
Taiwan are donepezil and rivastigmine. The Bureau of National Health
Insurance has asked the Society of Psychiatry and the Society of
Neurology to organize a task force to set up guidelines for the treatment
of AD. The guidelines for prescribing these drugs are 1) the patient has
to fulfill the diagnostic criteria for dementia of Alzheimer type according
to NINCDS-ADRDA, or DSM-IV, or ICD-10 and be diagnosed by neurologist
or psychiatrist. 2) The severity should be at mild or moderate level,
that is the CDR should be in grade 1 or 2, or the total score of the MMSE
should be between 10 to 26. 3) The patient should be followed for at
least 6 months. The drug should be withdrawn if the CDR has decreased
1 level or the total score of the MMSE decreases 2 points compared to
the initial treatment condition. 4) No past history of stroke or vascular
dementia. 5) Patient is without severe heart block. 6) The Bureau of
National Health must approve before these drugs can be prescribed.
Although we have relatively straightforward guidelines, the Department
of Health still encourages all new drug trials for the treatment of AD. —Donny Hin-Yeung Tsang (d840040@cc.kmc.edu.tw)
In Thailand the approval process for new drugs has two stages. The
Food and Drug Administration determines whether a product can be
marketed under a “sick monitoring program” for about two years. Then
the pharmaceutical company recommends that the committee to justify
the drug as a “National Essential Drug”. This classification makes medications
available for people who are under the social security scheme
all over the country.
Donepezil was approved for marketing in May 1998. Rivastigamine was
approved for marketing in July 1998. Both of their applications for
Essential Drugs listing have been turned down because of low economic
status. However, they are available in every medical school hospital as
well as at qualified hospital centers that justify subsidy of the drug on
the government services and state enterprises, as well as for large corporations.
The rules for prescribing subsidized anti-dementia drugs are
under approval by psychiatrists and neurologists. It is expected that
galantamine will be approved towards the middle of 2001. —Raviwan
Nivataphand (ekasan@ksc.th.com)
Two cholinesterase inhibitors are marketed in Turkey: donezepil 5 mg
tablet, and rivastigmine 1.5,3,4.5,6 mg capsule. Tacrine is not available
in Turkey. Donezepil was approved for marketing on November 5, 1998,
and it became available on National Health Insurance from March 6,
1999. Donepezil is prescribed more than rivastigmine. The monthly cost
of a therapeutic dose (10mg /day) is $US99.97. Rivastigmine has been
available since April 8, 1999. The monthly costs for a therapeutic dose
range from. $US86.1 to $US90. Prescription of CIs is not regulated.
There are no national guidelines for the use of CIs. Suitable patients for
prescription are those suffering from mild to moderate AD. Most of the
cholinesterase inhibitors are prescribed by psychiatrists, neurologists and
geriatricians. — Engin Eker (eneker@istanbul.edu.tr)
In the UK, drugs are licensed by the Committee on Safety of Medicines,
which is principally concerned with safety and efficacy of compounds.
All three cholinesterase inhibitors (donepezil, rivastigmine and galantamine)
have been approved. However, within the last few years the UK
government has set up a new institute, The National Institute for
Clinical Excellence (NICE) which provides the National Health Service
(NHS) with guidance on the use of different technologies, including
drug treatments. NICE does not automatically review all new treatments
yet, but given the controversy associated with the use of antidementia
agents this was one of the “technologies” it was asked to look at last
year. Unlike the Committee on Safety of Medicines, NICE is more concerned
with cost effectiveness and other benefits. It considered all three
treatments together, commissioned an independent economic analysis
and invited various interested bodies (including a number of experts
and institutions like the Royal College of Psychiatrists, the Alzheimer’s
Society and the British Geriatrics Society) to submit evidence.
It announced its decision in January 2001, that all three compounds
should be made available in the NHS as “one component of the management
of those people with mild and moderate AD.” Specific requirements
were that treatment could only be instituted for those whose MMSE score
was above 12, that diagnosis had to be made by a specialist according to
standard diagnostic criteria and that before treatment, assessments of cognition;
global and behavioral functioning and ADL should be performed.
Compliance had to be ensured and treatment could only be initiated by
Specialist Secondary Care Physicians (including Old Age Psychiatrists,
Neurologists and Care of the Elderly Physicians).
A further assessment should be made two to four months after reaching
maintenance dose and drugs should be continued only when there is
clear evidence of efficacy, this being defined as: improvement or no deterioration
in MMSE score together with evidence of global improvement
on the basis of behavioral and/or functional assessment. Patients should
be monitored every six months and the drug “normally” only continued
when their Mini-Mental State score remained above 12. This guidance
has been broadly welcomed by both patient organizations and clinicians
and now creates a level of equitable access that was not previously available
(“postcode prescribing” where some Health Authorities had funded
these agents and some had not had been the situation previously).
Some aspects of the NICE guidance have puzzled clinicians, particularly
the reliance on an MMSE score of above 12, where most of the trials
have included patients above 10, a decision clearly founded on economic
grounds. Suggestions are made for future research, including possible
long-term adverse events, treatment in severe dementia, management of
non-cognitive symptoms and efficacy in other dementias. The take-up of
such treatments in the UK is still relatively modest compared to
many others countries. This reflects, at least in part, the lack of extra
resources regarding the additional workload that accompanies the
new treatments. The full UK NICE guidance can be perused on
www.NICE.org.UK. —John O’Brien (j.t.o’brien@ncl.ac.uk)
In the USA, donepezil, rivastigmine and galantamine are all available.
There is no government subsidy for these drugs under the
Medicare federal government insurance for geriatric patients,
although some form of pharmacy benefit is expected to come from
legislation in the future. Private insurers cover these drugs with different
degrees of payment, and often require repeated documentation
of the diagnosis of probable AD and evidence of “therapeutic benefit.”
The drug manufacturers all have patient assistance programs
that in my experience have been very responsive to needy patients.
However, they do have an income cut-off that leaves many patients
without assistance for the expensive medications. — Bev Jones
(bjones@wfubmc.edu)
Donezepil and rivastigmine are on the list of drugs registered by 31st
December 1999 in Yugoslavia. They are marketed without being
approved for reimbursement, so just a few of the patients for whom
they are indicated can afford them, unless they are among the small
number included in a research project on rivastigamine at a neurology
clinic. —Aleksandra Milicevic–Kalaic (aleksandrak@excite.com)
Alzheimer’s Disease International publishes information about
anti-dementia drug availability in various countries in tabular form.
This information can be obtained at www.alz.co.uk/intranet.
