Kidney injury can be added to the list of possible harms related to use of three antipsychotic medications often prescribed to treat behavioral symptoms of dementia in older adults, a new study finds.

Quetiapine (Seroquel), risperidone (Risperdal) and olanzapine (Zyprexa) are approved by the U.S. Food and Drug Administration to treat bipolar disorder, schizophrenia and other serious mental disorders. They are also frequently used "off-label" to treat behavioral concerns such as aggression or agitation in seniors with Alzheimer's and similar neurodegenerative diseases.

"The side effect profile with antipsychotics is particularly concerning, so there is ample evidence to worry about their use in older adults unless they're absolutely necessary," said Dr. Anton Porsteinsson, director of Alzheimer's disease care, research and education at the University of Rochester School of Medicine and Dentistry in Rochester, N.Y. "This is basically just one more weight on the scale in disfavor of using antipsychotics in the elderly."

The study, published Aug. 19 in Annals of Internal Medicine, found that acute kidney injury was one and a half times more likely in older adults taking Seroquel, Risperdal or Zyprexa compared to similar adults not taking these medications.

It also found that the risk of low blood pressure and acute urinary retention (the inability to empty the bladder) doubled, and the risk of death from any cause more than doubled in older adults taking these drugs. The antipsychotics were linked to an increased risk of pneumonia and heart attack as well.

Although the study doesn't prove a direct cause-and-effect relationship between these drugs and kidney damage, experts say it adds to existing concerns.

"I understand why people are turning to these medications when older people are difficult to manage and you're trying to help them live with dignity, but I think they're being used a little indiscriminately," said study researcher and epidemiologist Dr. Amit Garg, of the London Health Sciences Center in Ontario, Canada. "Many agencies have said we need to be much more cautious with their use.

The drugs have carried a black-box warning from the FDA since 2005, after analysis of 17 randomized, controlled trials showed that older patients with dementia who took these drugs were up to 1.7 times more likely to die during the study period than those given a placebo.

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Their off-label use to treat difficult behavior in the elderly has previously been linked to drowsiness, falls, weight gain and serious health conditions, including stroke, pneumonia and death from any cause. But, "this is the first time these medications have been linked in a meaningful, robust way to kidney injury," Garg said.

Using health care database records from 2003 to 2012 in Ontario, Garg and his colleagues looked at the rates of acute kidney injury and other conditions among more than 97,000 adults, aged 65 and older, in the first three months after they began taking Seroquel, Risperdal or Zyprexa. These rates were compared to those among an equal number of adults not taking the medications and matched to the first group by age, sex, living arrangements and similar health or medical conditions. Participants' average age was 81, and a little over half had dementia.

One percent of adults taking the antipsychotics were hospitalized for acute kidney injury, compared to 0.6 percent of adults not taking the medications. And 6.8 percent of adults taking the antipsychotics died from any cause, compared to 3.1 percent of adults not taking the drugs.

Garg and Porsteinsson acknowledged that these mental health medications can be appropriate for adults with true psychosis.

"There are certain situations where there is no alternative when people are psychotic, and these drugs can make a major difference in outcomes for those individuals," Porsteinsson said, "but their use has to be balanced, not used simply for sleep impairments or anxiety."

Porsteinsson said behavioral problems in adults with dementia can result from factors such as pain, hunger, undiagnosed medical conditions or environmental triggers. These should be investigated first, he said.

"Is their room too hot or too cold? Do they truly dislike their roommate in a shared room? Do they have some unmet need?" Porsteinsson suggested. "They cannot communicate their needs so there's a lot of thoughtful detective work that needs to go into this."

If a regularly visiting family member misses a week, for example, the older adult may feel distressed or abandoned or worried, he said. In such situations, the first treatment should be trying to address those needs or trying to distract or redirect the older adult.

"Get them involved in some sort of activity that basically channels their restlessness or their unbridled energy into something a little more constructive," Porsteinsson said. "If that doesn't work, then you think medications."

More information

The U.S. National Institute of Mental Health has more about mental health medications.

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