Skip to main content

Antipsychotics Worsen Delirium and Make You Die (Slightly) Faster…



Antipsychotics are often used to treat delirium, although the evidence behind their efficacy is pretty minimal.   That evidence is even worse when it comes to patients with advanced illness or those nearing the end of their lives.    This week’s JAMA IM gives us the first placebo-controlled trial of two antipsychotics, risperidone and haloperidol, in relieving symptoms of delirium associated with distress among patients receiving palliative care.   The results do not look good for antipsychotics.

The Study

This was a randomized controlled, double-blind clinical trial done in eleven Australian inpatient hospice or hospital palliative care services.  Patients all had life-limiting illness, delirium, and symptoms of delirium that are associated with distress (inappropriate behavior, inappropriate communication, and illusions or hallucinations).

The participants received either placebo or pretty conservative age-adjusted doses of oral risperidone or haloperidol every 12 hours for 72 hours, titrated based on symptoms of delirium.   All of the patients, no matter what they were randomized to, receive individualized treatment of delirium precipitants and other measures (hydration, vision and hearing aids, presence of family, and reorientation).   Subcutaneous midazolam was available to all groups if required for severe distress or safety.

The Results:

In the primary intention-to-treat analysis, those who received risperidone or haloperidol had significantly worse delirium symptom scores and delirium severity scores than those among participants in the placebo arm.

Not only did they have worse delirium scores and severity scores, the antipsychotic group had more extrapyramidal effects and worse overall survival (although for risperdone this didn’t reach significance).

Lastly, use of rescue midazolam was significantly lower in the placebo group versus those who took an antipsychotic.

The take home

I’ll just finish up with a quote from the accompanying editorial:
“Using antipsychotic drugs to treat delirium in terminally ill patients, not only are they not reducing distress but they are in fact worsening patients’ symptoms.”
While that sums up my thoughts nicely, I do have to wonder though about the use of a benzodiazepine as a rescue medication, and how that influences the results of the study.   The overall consensus is that we should avoid benzodiazepines in delirium except for very limited indications (i.e. alcohol withdrawal, seizures).   Even when using it for "terminal" delirium, the use of benzodiazepines is questionable as it really is a diagnosis done in hindsight (you only really know its terminal delirium when someone died with delirium).  Use of a benzodiazepine probably made the situation even worse for the group that used more of it (the antipsychotic group), but it probably doesn’t change the fact that antipsychotics made people initially do worse so they needed more of the rescue.

Kaplan-Meier Survival Curve for all 3 groups 
The other very big caution is not to generalize these results outside of those included in this study.   These folks were sick.  I mean very sick.  Median survival in the placebo group was 26 days compared to 16 and 17 days in the haloperidol and risperidone groups.   The Kaplan-Meier Survival curve for all groups, including placebo, looks like a line art drawing of the White Cliffs of Dover.  

Is there a role of antipsychotics for healthier individuals with delirium in which we are not making things worse by giving a benzodiazepine as a rescue?  Maybe.  Maybe not.   Not sure I can say so with the results of this trial.

What do you think?

by: Eric Widera (@ewidera)



Comments

PaoBhangra said…
The problem largely is that these patients were all going to die soon (albeit time span here could be a wide range) If you enter the death trajectory with a benzo or haldol or risperdal can u really then,say that these,drugs sped up the death curve. Its not like the placebo folks had a great time either. Severe agitation in dementia remains a unsolved Gordian knot. I have had some great results w haldol and some where the next step was versed sedation unfortunately. I cannot ignore the significant good results. And yet have to acknowledge the worse ones.
Dani Chammas said…
I think the struggle in these cases is that we always want to "try something." Even when there wasn't "great" evidence for it, it still always felt right to "try" in the hopes to alleviate distress (... not to mention the value to caregivers and clinicians of feeling like they are doing something). What's troubling about this study is that it actually found that symptoms/distress were WORSE in this population... which really does put us in a conundrum.
Andrew Kamell said…
This may be the first time I have been really shocked at the results of a study. Based on experience & my reading of previous studies, I have always believed that use of antipsychotics is helpful for "positive" symptoms of delirium (hallucinations, delusions/paranoia in the absence of withdrawal) though NOT helpful for hypoactive delirium, dementia, or agitation itself.
Since this study used it for ALL patients with any symptoms of delirium (likely including some with solely dementia,) it is still possible it may be beneficial for the subset with "positive" symptoms, while harming others. I must say, this study has me a bit stumped. And if the result is more use of BZD's, I am very concerned!
Anonymous said…
I read the article and the accompanying editorial. I understand the risks and the results of this study. But as a clinician, when facing a delirious patient in distress, especially in the presence of family and helpless hospital staff, all eyes turn to you to "do something". Of course reversible causes of delirium must be identified and treated; however most often it is not until all causes have been explored and all treatments exhausted that palliative care is called to consult. The editorial alludes to nebulous non-pharmacological ("ecobiopsychosocial")interventions but does not offer realistic, concrete examples of alternative approaches. It is not reassuring at all for caregivers to hear that they themselves need counseling, when their demented loved one is constantly yelling, and crawling over the guardrails posing a fall risk to themselves and driving staff crazy. Until realistic, alternative and effective approaches can be identified and made widespread, I highly doubt the practice of using antipsychotics for agitated delirium will change.

Popular posts from this blog

Practical Advice for the End of Life: A Podcast with BJ Miller

This week we talk with BJ Miller, hospice and palliative care physician, public speaker, and now author with Shoshana Berger of the book "A Beginner's Guide to the End."

As we note on the podcast, BJ is about as close as we get to a celebrity in Hospice and Palliative Care.  His TED Talk "What Really Matters at the End of Life" has been viewed more than 9 million times.  As we discuss on the Podcast, this has changed BJ's life, and he spends most of his working time engaged in public speaking, being the public "face" of the hospice and palliative care movement.

The book he and Berger wrote is filled to the brim with practical advice.  I mean, nuts and bolts practical advice.  Things like:
How to clean out not only your emotional house but your physical house (turns out there are services for that!)Posting about your illness on social media (should you post to Facebook)What is the difference between a funeral home and mortuaryCan I afford to die?  …

Improving Advance Care Planning for Latinos with Cancer: A Podcast with Fischer and Fink

In this week's GeriPal podcast we talk with Stacy Fischer, MD and Regina Fink, RN, PhD, both from the University of Colorado, about a lay health navigator intervention to improve advance care planning with Latinos with advanced cancer.  The issue of lay health navigators raises several issues that we discuss, including:
What is a lay health navigator?What do they do?  How are they trained?What do lay health navigators offer that specialized palliative care doesn't?  Are they replacing us?What makes the health navigator intervention particularly appropriate for Latinos and rural individuals?  For advance care planning? Eric and I had fun singing in French (yes French, not Spanish, listen to the podcast to learn why).
Enjoy! -@AlexSmithMD




You can also find us onYoutube!



Listen to GeriPal Podcasts on:
iTunes Google Play MusicSoundcloudStitcher

Transcript

Eric: Welcome to the GeriPal podcast. This is Eric Widera.

Alex: This is Alex Smith.

Eric: And Alex, I'm really excited about toda…

The Dangers of Fleet Enemas

The dangers of oral sodium phosphate preparations are fairly well known in the medical community. In 2006 the FDA issued it’s first warning that patients taking oral sodium phosphate preparations are at risk for potential for acute kidney injury. Two years later, over-the-counter preparations of these drugs were voluntarily withdrawn by the manufacturers.  Those agents still available by prescription were given black box warnings mainly due to acute phosphate nephropathy that can result in renal failure, especially in older adults. Despite all this talk of oral preparations, little was mentioned about a sodium phosphate preparation that is still available over-the-counter – the Fleet enema.

Why Oral Sodium Phosphate Preparations Are Dangerous 

Before we go into the risks of Fleet enemas, lets spend just a couple sentences on why oral sodium phosphate preparations carry significant risks. First, oral sodium phosphate preparations can cause significant fluid shifts within the colon …