Current alzheimer's medications: effective treatment options, or expensive bottles of hope?
some people with early- to moderate-stage AD score may not beaccurately measureThe ADAS-Cog, according to 2 studies re-
ported in 2012, is a test instrument “not subtle enough to properly
track changes in the early stages of Alzheimer’s.A major studyconducted by Consumer Reports in 201concluded that thedifferences in scores on the ADAS-Cog for patients taking any of theFDA-approved medications, when compared with placebo groups,
are “smaller than 4 points, which is so small, it is not considered
I am not a medical researcher, nor am I a medical doctor. I am,
meaningful.” Consumer Reports also concluded that the “small
however, a spouse caregiver for my wife, who is now in moderate
improvements” showing slower rates of decline in activities of daily
stages of Alzheimer disease (AD). My reading of the AD literature,
living as measured by various instruments “would not be consid-
my listening to other spouse caregivers, and my research on the
ered clinically meaningful by most doctors.”
effectiveness of current AD medications all tell me that doctors too
The second research ﬂaw is that clinical trials cited as evidence
often recommend that patients with AD continue taking ineffective
of the effectiveness of these medications are few, and of very brief
“treatment medications.” Well after the time period when even the
duration, with absolutely no data supporting any positive outcomes
pharmaceutical manufacturers claim that their products are effec-
beyond that clinical trial duration. I would think that if any phar-
tive, many doctors continue to prescribe these same ineffective AD
maceutical manufacturer had any evidence of its medication having
any positive effects beyond the duration of their brief clinical trials,that evidence would be made public . in a heartbeat!
All had clinical trials of short duration, all of the positive effects
were leveling off or slowing down by the end of the trials, and all
My wife took 2 of the most commonly prescribed AD medica-
testing was with instruments that are not necessarily the best
tions: donepezil (Aricept) and memantine (Namenda). Along with
measurements of cognitive performance.
galantamine (Razadyne) and rivastigmine (Exelon), these are 4 of
The Web site of Ortho-McNeil Neurologics, a division of Ortho-
the 5 prescription medications that have been approved by the US
McNeil-Janssen Pharmaceuticals, Inc., cites only 4 randomized,
Food and Drug Administration (FDA) to treat people diagnosed with
double-blind, placebo-controlled clinical investigations for galant-
AD. A ﬁfth medication, tacrine (Cognex), was also approved by the
amine in patients with probable Using the ADAS-Cog to assess
FDA, but is now rarely prescribed because of safety All
cognitive performance, the 4 trials lasted 21, 26, 26, and 13 weeks,
but memantine are termed “cholinesterase inhibitors” that
respectively. At the end of these short-duration trials, results had
“prevent the breakdown of acetylcholine, a brain chemical believed
already either leveled off or begun to decline, even for the groups
to be important for memory and thinking.”Memantine works
demonstrating initial improvement. There is not even one study
differently, by regulating glutamate, a brain chemical that, “when
demonstrating that galantamine is effective to any degree whatsoever
produced in excessive amounts, may lead to brain cell death.Each
of these medications carries the possibility for side effects, such as
On the Novartis Web site, one ﬁnds data from 5 clinical trials
nausea, vomiting, or diarrhea, to name a few.
with patients with AD that lasted 12, 24, and 48 weeks usingrivastigmine in oral or “patch” form, and all relied on the ADAS-Cog
and MMSE to measure outcomes. All trial results show that even forthe groups demonstrating improvement on the medication,
Although there is absolutely no research to indicate that any of
declines in scores appear after 24 weeks. There is not even one study
these medications will stop or cure AD, there is some research to
demonstrating that rivastigmine is effective to any degree whatsoever
indicate that, for some patients, these medications may slow the
rate of decline for a brief period of time. However, this research is
On the Eisai/Pﬁzer Web site, one ﬁnds data from 4 clinical trials
based on only a few clinical trials of very short duration, and this
with patients with AD taking donepezil. Two trials were for
research is badly ﬂawed in 2 major respects.
patients with mild to moderate AD, 1 for 15 weeks and 1 for 30
The ﬁrst research ﬂaw is that the “signiﬁcant positive outcomes”
weeks. Two trials were for patients with moderate to severe AD, for
obtained in clinical trials cited by drug manufacturers as “evidence”
24 weeks in Japan and 6 months in Sweden. Once again, even for
of the effectiveness of their medications are usually based on
groups demonstrating improvement on this medication, declines in
results obtained on the Mini-Mental State Examination (MMSE) or
scores begin at or before the 24-week stage as measured by the
Alzheimer’s Disease Assessment ScaleeCognitive (ADAS-Cog) tests.
ADAS-Cog and other instruments. There is not even one study
The MMSE, a commonly used AD screening test, is an instrument
demonstrating that donepezil (Aricept) is effective to any degree
that was never designed to diagnose AD, and cognitive declines in
Letters to the Editor / JAMDA 14 (2013) 525e527
The Research Center of the Alzheimer’s Association provides
much information about treatments for AD. Their conclusion with
What do all clinical trials using cholinesterase inhibitors tell us?
respect to current medication is this: “On average, the ﬁve
Very simply, we learn that of the 11 clinical trials for these 3
approved Alzheimer’s drugs are effective for about sixe12 months
medications, 9 of them lasted for 26 weeks or less. We also learn
for about half of the individuals who take them.
that in every study, even patients showing initial evidence of
The National Institutes of Health also recently afﬁrmed that these
improvement started to decline after 24 weeks, if not sooner.
AD medications are largely ineffective beyond a limited period of
And, ﬁnally, we learn that there is absolutely no evidence indi-
time. The executive summary of its comprehensive “Alzheimer’s
cating that patients continuing to take these medications beyond
Disease Progress Report,” 2011e2012, concludes that the current
a very limited period of time, 1 year or less, will continue to demon-
FDA-approved AD medications “may help some people” . but even
strate any positive effects these medications may have had.
for those it does help, it is “only for months to a couple of years.”
And what do we learn from clinical trials about the evidence of
effectiveness of memantine? On the Forest Laboratories, Inc., Website, 2 studies are reported, 1 lasting 24 weeks and 1 for 28 weeks.
Outcomes were measured using 2 instruments, 1 to measure
activities of daily living and 1 to measure cognitive function. In the28-week study, after 4 weeks, the group receiving a placebo started
Doctors should deﬁnitely prescribe AD medications for several
to decline; the group receiving memantine showed a slight
months and even up to a year or 2 if they or their patients or
improvement for 12 weeks, and then started to decline. In the 24-
caregivers see positive effects. But doctors should not recommend
week study, the treatment groups were different. One group
that patients continue taking these medications once they are
received memantine and donepezil, whereas the other group
obviously ineffective. This practice must stop.
received memantine and a placebo. After 4 weeks, the group
Doctors must accept that AD medications eventually become
receiving memantine and the placebo started to decline, whereas
expensive “bottles of hope” that will not slow down the inevitable
the group receiving memantine and donepezil did not show
degenerative progression of AD. Doctors must also accept that, by
declines until the 8-week point. There is not even one study
continuing to prescribe these medications year after year, long after
demonstrating that memantine (Namenda), given with or without
they can possibly still be helpful, they may unintentionally be doing
donepezil, is effective to any degree whatsoever beyond 28
their patients and caregivers more harm than good.
Despite there being no research to support the effectiveness of
these AD medications beyond a few months, at best, many doctorscontinue prescribing these medications for years and years. Notonly can these AD medications no longer be helping their patients,
but they may actually be causing some harm. Maintaining patientson these medications long term may provide false hope to patients
1. National Institutes of Health, US Department of Health and Human Services.
Alzheimer’s disease medications fact sheet. July 2010; updated March 22, 2013.
and their caregivers. I refer to these medications as “bottles of
hope” because as I watch my wife decline, I know that the medi-
cations cannot possibly be helping anymore, if they ever did at all.
2. Vann A. Listen more carefully to Alzheimer’s caregivers. J Am Geriatr Soc 2012;
For many patients and caregivers, the high costs of AD medi-
3. Cognitive test in Alzheimer’s drug trial may be ﬂawed. Science Daily. Available
cations present an economic hardship. Money spent on AD medi-
cations is money that might otherwise be spent on day care
4. Evaluating prescription drugs used to treat: Alzheimer’s disease. Consumer
programs, companions, home health aides, or other services that
would actually improve the quality of their lives.
Another problem with continuing to take these medications for
5. Razadyne. Full US prescribing information. Titusville, NJ: Ortho-McNeil-Janssen
Pharmaceuticals, Inc. pp. 2e4. Available at:
many years may be long-term negative side effects. Negative side
effects were reported to some degree in all of the short-duration
6. Exelon. Highlights of prescribing information. East Hanover, NJ: Novartis. pp.
clinical trials, but there are no data on long-term negative side
13e16. Available at: 2006. Accessed January 15, 2013.
effects. Side effects not initially apparent may surface after
7. Aricept. Highlights of prescribing information. Woodcliff Lake, NJ: Eisai, Inc.
continuing to take these medications year after year.
Doctors must be realistic and honest with both patient and
caregiver. Absent research to the contrary, doctors should recom-
8. Namenda. Full prescribing information. St Louis, MO: Forest Pharmaceuticals.
mend that their patients discontinue taking these medications after
9. Evaluating prescription drugs used to treat: Alzheimer’s disease. Consumer
The Best Buy Drugs Report, issued by Consumers Union in May
10. Alzheimer’s Association, Research Center, Science & Progress Treatment
2012, was not given much publicity until excerpts appeared in the
Horizon section. Five FDA-approved Alzheimer’s drugs. Available at:
Washington Post on January 7, 2013. Consumers Union, which
reviewed more than 1100 research studies and articles on AD
11. National Institutes of Health, National Institute on Aging. A primer on Alzheimer’s
medications, begins the recommendations section of their
disease and the brain. NIH Alzheimer’s Disease Progress Report, 2011e2012, p. 9.
comprehensive 2012 report with this statement: “The medications
used to treat mental decline in people with Alzheimer’s disease are
not particularly effective. When compared to a placebo, mostpeople who take one will not experience a meaningful beneﬁt. And
it is the rare person who has a signiﬁcant delay in the worsening
of their symptoms over time.The recommendations pageconcludes with these words, “if the person taking the drugs does
not show signs of improvement within three months, it is unlikelythey ever will, so the drug should then be stopped.”
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