Alzheimer's: Two Drugs Better Than One
Study Shows Slowest Disease Progression With Combo Treatment
By
Salynn Boyles
WebMD Health News
Reviewed By
Louise Chang, MD
Sept. 25, 2008 -- Treating Alzheimer's patients with a combination of the two types of drugs now approved for the disease is
better than no treatment for delaying the progression of symptoms.
That is the finding from one of the first long-term, independent studies to
examine the effectiveness of Alzheimer's medications.
Researchers stopped short of saying that combination treatment modifies the
course of disease by protecting brain cells from the damage that leads to the
memory and functional declines characteristic of Alzheimer's disease.
But lead researcher Alireza Atri, MD, PhD, of Massachusetts General Hospital
and Harvard Medical School suspects that treatment can slow disease
progression.
"My gut feeling is that there is a small degree of disease modifying
going on with treatment and a fair degree of symptom benefit," he tells
WebMD.
Alzheimer's Drugs Examined
More than 5 million people in the United States are believed to have
Alzheimer's disease, and that number is projected to more than triple within
the next four decades.
Two classes of drugs are now approved to treat the disorder: cholinesterase
inhibitors like the drugs Aricept, Exelon and Razadyne, and the drug
Namenda.
The cholinesterase inhibitors target acetycholine, a chemical messenger
believed to be important for memory and mental alertness. They are all approved
for mild to moderate Alzheimer's disease. Aricept is also approved for
treatment of moderate to severe Alzheimer's.
Namenda was the first drug approved by the FDA for the treatment of moderate
to severe Alzheimer's. It is believed to work by regulating glutamate, another
neurotransmitter linked to memory and learning.
Both classes of drugs showed some efficacy in short-term industry studies
conducted to win FDA approval, but longer studies examining their usefulness in
real-world settings have not been done, Atri says.
"There has been a lot of debate about whether these drugs work or
whether they only work for some patients for a limited amount of time,"
Atri says.
The fact that patients may continue to experience declines in memory and
other aspects of mental functioning while taking the drugs makes it difficult
to evaluate their effectiveness, he adds.
Longer Treatment Better
In an effort to address this issue, Atri and colleagues followed 382
Alzheimer's patients for an average of 2 1/2 years, assessing their mental and
functional abilities every six months using standardized testing protocols.
A total of 144 patients received no drug treatment, 122 were treated with a
cholinesterase inhibitor alone, and 116 took a cholinesterase inhibitor in
combination with Namenda.
After controlling for factors associated with disease progression, including
duration of illness and age, the researchers concluded that patients taking the
combination of drugs had the smallest memory and functional declines.
Using a statistical model that they developed, they predicted that the
longer patients stayed on the combination treatment, the smaller their rate of
decline would be.
"Initial response when patients are put on these drugs is not really a
good predictor of whether they are working," Atri says. "As time goes
on the benefits become more apparent."
Other Approaches to Treatment
The researchers conclude that their study raises "the intriguing
possibility that combination therapy modestly modifies the long-term clinical
course of Alzheimer's disease."
But Alzheimer's researcher and clinician Constantine G. Lyketsos, MD, says
the findings do little to change his opinion that the currently available drugs
do not modify the course of the disease.
Lyketsos leads the psychiatry department at Baltimore's John's Hopkins
Bayview Medical Center.
"This was not a randomized trial, and that is a problem," he says.
"It may be that the patients on the combination treatment were healthier to
begin with and could tolerate more aggressive treatment."
Lyketsos says there is now general agreement that the approved Alzheimer's
drugs can have a "small to modest" impact on symptoms, but he adds that
medication is just one component of treatment.
Counseling and respite for caregivers, providing activities for patients,
treating psychiatric symptoms like depression, and getting patients
off other medications that they may not need are also important aspects of a
comprehensive treatment plan, he says.
"Good dementia care should include a conversation with the health provider about whether drugs are needed, but it
certainly isn't limited to that," he says.
SOURCES: Atri, A. Alzheimer's Disease and Associated Disorders,
July/September, 2008; online edition. Alireza Atri, MD, PhD, department of neurology and Massachusetts Alzheimer's
Disease Research Center, Massachusetts General Hospital; Harvard Medical
School, Boston. Constantine G. Lyketsos, MD, Althouse Professor and Chair of Psychiatry,
Johns Hopkins Bayview Medical Center, Baltimore.
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