Alzheimer’s: Two Drugs Better Than One

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."