Drugs used for anxiety, sleep are linked to Alzheimer's disease in older people

Older people who have relied on a class of drugs called benzodiazepines to reduce anxiety or induce sleep are at higher risk of going on to develop Alzheimer's disease, new research finds, with those whose use of the medications is most intensive almost twice as likely to develop the mind-robbing disorder.

Benzodiazepines -- marketed under such names as as Xanax, Valium, Ativan and Klonopin -- are widely used to treat insomnia, agitation and anxiety, all of which can be early signs of impending Alzheimer's disease in the elderly. But the current study sought to disentangle benzodiazepines' use in treating early dementia symptoms, probing instead the possibility that heavy use of the medications may permit, cause or hasten the onset of Alzheimer's dementia.

The study compared the pattern of benzodiazepine use in 1,796 elderly people diagnosed with Alzheimer's with that of 7,184 similar people who had no such diagnosis. Such a study design, conducted by French and Canadian researchers and published Tuesday in the journal BMJ, cannot by itself establish that more intensive use of the medications causes Alzheimer's disease. But it does strengthen such suspicions.

Among the study participants over 66 who were living independently in the Canadian province of Quebec, those who took low-dose benzodiazepine medication, or who took higher doses but very briefly or infrequently, did not see their Alzheimer's risk go up five years after they were first prescribed such a medication. But the picture was more worrisome for those who frequently took long-acting benzodiazepines, who frequently took high doses, or who took any such drugs regularly over several months.

The benzodiazepines specifically considered by the researchers were the short-acting anti-anxiety medications alprazolam (Xanax), lorazepam (Ativan), oxazepam (Seresta) and diazepam (Valium), and the longer-acting anti-seizure and "hypnotic" drugs frequently used to treat insomnia: clonazepam (Klonopin), flurazepam (Dalmane), midazolam (Versed), nitrazepam (Mogadon), temazepam (Restoril) and triazolam (Halcion).
The widely prescribed prescribed medicines marketed as Ambien, Lunesta and Sonata (generically named zolpidem, eszopiclone and zaleplon) are "atypical benzodiazepines" and were not included in the analysis.

The authors of the study created an index that gauged the intensity of a participant's benzodiazepine use and found that at the end of a five-year period following an initial prescription, Alzheimer's risk mounted steadily. Those who took the cumulative equivalent of daily doses for three to six months over a five-year period were roughly 32% more likely than those who took none to develop Alzheimer's. Those who took the cumulative equivalent of a full daily dose for more than six months were 84% more likely to do so.

There's already strong research evidence that frequent or regular benzodiazepine use degrades memory and mental performance in humans and animals. And some research suggests that with regular use of this class of drugs, the receptors to which they bind in the brain become less active. And lower activity of those receptors has been linked to cognitive decline.

"In view of the evidence, it is now crucial to encourage physicians to carefully balance the risks and benefits when initiating or renewing a treatment with benzodiazepines and related products in older patients," the authors wrote.

International medical guidelines recommend the use of benzodiazepines as treatment for anxiety disorders and transient insomnia, but caution that they are not meant for long-term use, and should not be taken steadily for more than three months. But many patients continue to take these drugs for years. In addition to their cognitive effects, benzodiazepines are widely implicated in the national epidemic of opioid pain medication overdoses and fatalities that result from mixing them with alcohol and opioid drugs.

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Dr David Marcon
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