Antipsychotics and Dementia: A Few Bad Apples?

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Alvin B. Lin, MD, FAAFP

Associate Professor of Family and Community Medicine, University of Nevada School of Medicine

Adjunct Professor of Family Medicine and Geriatrics, Touro University Nevada College of Medicine

Advisory Medical Director, Infinity Hospice Care

Medical Director, Lions HealthFirst Foundation

Dr. Lin maintains a small private practice in Las Vegas, NV. The posts represent the views of Dr. Lin, and in no way are to be construed as representative of the above listed organizations. Dr. Lin blogs about current medical literature and news at


Scientifically speaking, one bad apple can spoil the whole barrel. That phrase applies figuratively, too. Nationally and internationally, think about the effect performance enhancing drug use has had on professional sporting events. And locally, a few wayward physicians have branded the rest of us, who do attempt to do our best for our patients, as money-grubbing quacks. Well, a few years ago, all antipsychotics, both typical and atypical, were given a black box warning by the Food & Drug Administration since multiple observational studies had demonstrated an increase in mortality associated with their use in patients with dementia.

Previously, all the atypical antipsychotics, while supposedly less likely to cause extrapyramidal symptoms and tardive dyskinesia, had been lumped together as increasing one's risk for weight gain, hyperglycemia, and dyslipidemia (which is why I've always cringed when I see patients taking these drugs to deal w/their insomnia, especially when they tell me that they haven't tried anything else).

Unfortunately, given the increasing numbers of patients with dementia requiring institutionalization, especially those with aggressive behaviors not ameliorable to nonpharmacologic therapies as well as those with egodystonic hallucinations and delusions, antipsychotic use remains high, if not rampant. The former is fairly apparent & clear cut to delineate. However, family members and staff often push for use of antipsychotics even in those patients with egosyntonic distractions.

In reality, let's say a demented loved one really and truly believes that Edward the vampire and Jacob the werewolf are her friends. There's no need to medicate this patient who is comforted rather than distressed. On the other hand, let's say this same demented loved one is deathly scared of the Easter Bunny who is lurking in the shadows. I think we'd all agree that this patient needs some medication assuming distraction, cognitive behavioral therapy and non-pharmacologic measures aren't enough (after ruling out new onset medical illness, of course).

This is a prelude to a retrospective analysis of a population-based cohort study published in the British Journal of Medicine in February of 75,445 elderly nursing home patients older than 65 years of age who were newly prescribed antipsychotics for the past 6 months. Compared to those given risperidone, those prescribed haloperidol had a two times greater all-cause mortality while those prescribed quetiapine had a 20% lower all-cause mortality. The other antipsychotics prescribed in large enough amounts to be assessed, aripiprazole, olanzapine, and ziaprasidone, did not show any statistically significant difference in all-cause mortality compared to risperdol.

No, we don't have randomized controlled trials to demonstrate cause and effect. And no, we don't have head-to-head trials to demonstrate which is the better drug. But for now, this study suggests that quetiapine might have just jumped to the head of the class. And we might want to get rid of that bad apple, haloperidol (well, at least have another discussion with family members regarding this new study).