Antipsychotics & Dementia: A Few Bad Apples?

Scientifically speaking, one bad apple can spoil the whole barrel.  That phrase applies figuratively, too.  Nationally & 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 & 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 w/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 w/dementia requiring instituionalization, especially those with aggressive behaviors not ameliorable to non-pharmacologic therapies as well as those with egodystonic hallucinations & delusions, antipsychotic use remains high, if not rampant.  The former is fairly apparent & clear cut to delineate.  However, family members & staff often push for use of antipsychotics even in those patients w/egosyntonic distractions.

In reality, let's say a demented loved one really & 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 last week of 75,445 elderly nursing home patients >65yo who were newly prescribed antipsychotics for the past 6 months.  Compared to those given risperidone, those prescribed haloperidol had a 2x 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 & ziaprasidone, did not show any statistically significant difference in all-cause mortality compared to risperidone.

No, we don't have randomized controlled trials to demonstrate cause & 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).

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