This Month’s Expert: Marc Agronin, M.D., on Treating Agitation in Dementia

This Month’s Expert: Marc Agronin, M.D., on Treating Agitation in DementiaTCR: Welcome back to The Carlat Report, Dr. Agronin. You were our expert in October of 2003 when we discussed the diagnosis of dementia, and I understand that since then you have been busy with a new textbook project.

Dr. Agronin: Yes, Dr. Gabe Maletta and I are editing the textbook Principles and Practices of Geriatric Psychiatry, which will be published later this year by Lippincott Williams & Wilkins.

TCR: Excellent – this means you’ve been keeping on top of the geriatric literature, and I hope you can clarify the significance of the recent FDA warnings on the use of atypical antipsychotics in the elderly.

Dr. Agronin: This scrutiny of antipsychotics began with the warnings of increased cerebrovascular adverse events with Risperdal, and somewhat later there were similar warnings regarding both Zyprexa and Abilify. This led the FDA to review a series of studies with antipsychotics in the elderly, and they found there were non-statistically-significant increases in mortality in the treatment groups, but because this difference was seen across all studies, they felt it was important to warn of a possible risk.

TCR: So the difference was not statistically significant, but the trend was consistent across studies of different atypical antipsychotics.

Dr. Agronin: Exactly. They analyzed 17 placebo-controlled trials and found that the risk of death in the drug-treated patients was 1.6 to 1.7 times greater than that seen in the placebo-treated patients. So in a typical ten-week trial, the rate of death in the drug treatment group is about 4.5% compared to about 2.6% in the placebo group.

TCR: And what were the usual causes of death?

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Dr. Agronin: Most commonly, they were either cardiovascular, such as heart failure or sudden death, or infectious, such as pneumonia.

TCR: It certainly seems like an odd finding. How might these drugs be leading to these deaths?

Dr. Agronin: It’s certainly not easy to say what’s going on here. There have been no consistent findings suggestive of cause for either stroke or cardiovascular events. In general, cardiac parameters, like heart rate, blood pressure, or even clotting factors, have not been found to be significantly different in treatment groups, so if this is an actual phenomenon, there is no clear pathophysiology, making it even murkier.

TCR: I’m imagining what I would tell the families of my patients with dementia: “In these three-month long studies of atypical antipsychotics, about 2% of the patients taking placebo pills died of various causes, while about 4% of patients who were put on one of the atypical antipsychotics died, and we don’t know how real this difference is, and if it is real, we don’t understand why this happens.”

Dr. Agronin: I think that is certainly one way to explain it. I usually talk to the families about the risks and benefits of treating the behaviors with the medication versus non-treatment. The risks of injury to themselves and other individuals, and the pain and suffering from being psychotic and agitated, are huge. And the benefit of medication is that we have a tremendous amount of data suggesting that it makes a real difference in helping these individuals. I emphasize the fact that we are dealing with a frail brain and also a frail body and this can amplify the risks of any medication. Usually, at that point, I mention that there have been recent warnings about the risks of certain side effects – potentially more cerebrovascular side effects and somewhat higher mortality rates – and we really have a discussion about that. I rarely encounter families who are very concerned about it. They understand that the individual is already suffering from a brain disease and understand the importance of doing something to relieve what they see as real pain and suffering.

TCR: Basically, this new FDA data is just one more piece of the puzzle that we put into our discussion of risks vs. benefits with patients.

Dr. Agronin: And it is critical to document this as well, because these warnings cause a fair amount of overreaction, not only on the part of physicians, but also on the part of nursing home administrators and pharmacy groups. I’ve noticed that physicians, nurse practitioners and pharmacists are often pressured to make medication decisions based on the potential for a nursing home to get sued. In my opinion, that is not practicing good medicine, and that is doing a disservice to patients, especially because the issue is not black and white. I would liken it to the situation with antidepressants in which people overreact to warnings; they don’t understand the complexity of it, and in the case of antidepressants, fewer people are being treated and that potentially causes more harm than good.

TCR: Are there any FDA-approved medications specifically for treating agitation in the elderly?

Dr. Agronin: No there aren’t, and it is such a significant problem. It doesn’t mean we can’t use the medications we have, but these days off-label use has come under greater scrutiny, even though it is often standard practice, and we base it on the literature and on professional standards. Just because something is not FDA-approved for an indication doesn’t mean that it doesn’t work; it often means that sufficient resources have not been put into doing the exact studies needed to receive approval.

TCR: Well, assuming that these warnings will affect physician behavior, what are some of the alternatives to using antipsychotics?

Dr. Agronin: Well, I am going to assert that there are no better alternatives. These are the only medications to treat psychosis and they are the best medications to treat agitation. They have the best data and ultimately they are the safest.

TCR: Are behavioral approaches ever effective for agitation in dementia?

Dr. Agronin: They are effective in mild cases of agitation, where we try to identify whether certain needs are not being met, and try to meet those needs if possible. Patients get hungry or thirsty, they need to be changed, they are constipated, they are uncomfortable, or they are in pain. Redirection is a common behavioral technique, and we can also make environmental changes to take away either excess noise or light. Increasing therapeutic activity can be important – for example, socialization, music therapy, art therapy, and so on.

TCR: What about the use of conventional antipsychotics rather than atypicals?

Dr. Agronin: Well, the guess is that these warnings are going to apply across the board. But we don’t have as much data on older medications as we have with the atypicals. We know with the conventionals that there are higher risks of anticholinergic side effects, dystonic reactions, and extrapyramidal side effects, so you are basically trading one side effect for another and, if anything, I would suggest that there is a worse profile with the conventionals.

TCR: What about other medications for agitation?

Dr. Agronin: They can be effective, but again, they also carry significant risks. Benzodiazepines, for example, carry an additional risk of falling related to dizziness and gait imbalance, and there are actually recent data showing that the rate of stroke on benzodiazepines was even higher than that reported for antipsychotics.

TCR: What about trazodone, which seems to be a favorite for nighttime agitation?

Dr. Agronin: There is only a single study with trazodone, comparing it with Haldol for agitation. In clinical practice, trazodone may help some people but it also carries a risk of sedation at higher doses, and it carries a risk of ventricular arrhythmias. Mood stabilizers are often useful, but you have a series of problematic side effects with both lithium and Depakote. So, again, if you ask any clinician, if you look at consensus guidelines, if you look in the literature, you always come back to the fact that the best data is with the atypical antipsychotics.

This Month’s Expert: Marc Agronin, M.D., on Treating Agitation in Dementia

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This article was published in print 8/2005 in Volume:Issue 3:8.


APA Reference
Agronin,, M. (2013). This Month’s Expert: Marc Agronin, M.D., on Treating Agitation in Dementia. Psych Central. Retrieved on December 4, 2020, from


Scientifically Reviewed
Last updated: 5 Aug 2013
Last reviewed: By John M. Grohol, Psy.D. on 5 Aug 2013
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