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Can We Use Rivastigmine for the Treatment of Antimuscarinic Delirium?

July 21, 2023

Written by Christian Gerhart

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In this small, retrospective review of 22 patients with antimuscarinic delirium who received antidotal therapy with transdermal +/- oral rivastigmine, there were no major adverse effects observed, and symptom resolution generally occurred within a matter of hours.

No physostigmine, no problem?
Antimuscarinic delirium (AD) can cause altered mental status in both the young and the old (diphenhydramine, Jimson weed and so many more). Historically, this has been treated with intravenous physostigmine, a central + peripheral acetylcholinesterase inhibitor. Recently, we have been faced with a stoppage in production from the lone physostigmine manufacturer in the U.S., which has forced a change in the treatment of AD to rivastigmine, another central + peripheral acetylcholinesterase inhibitor, that is only available in either oral (rivastigmine pills should not be crushed or altered) or transdermal formulations. There is a paucity of evidence for the effectiveness and safety of rivastigmine in the treatment of AD.

This was a small, retrospective case series of 22 patients aged 16-63 (median age 29) who were diagnosed with AD by a single board-certified medical toxicologist. All patients in this study were treated with the rivastigmine patch (generally the 13.3 mg dose), which was placed on the back to prevent inadvertent removal, and which stayed in place for 24 hours. Patients who were able to tolerate oral intake were also treated with 3-12 mg of oral rivastigmine. The median time to symptom resolution was 2 hours in patients treated with oral rivastigmine (all of whom were also treated with the transdermal patch) and 5 hours for those treated with the transdermal patch only. Rivastigmine appeared to be very safe. There were no seizures, episodes of symptomatic bradycardia, vomiting, diarrhea or new EKG changes observed.

Though this study has several limitations (no control group, no comparison to physostigmine, small sample size), it does provide some reassurance that rivastigmine is safe and may also be effective in the treatment of AD. Physostigmine has historically been feared due to the possibility of causing bradycardia or seizures, and this has led many toxicologists to not use it. Rivastigmine may be less likely to cause these side effects because of its slower absorption. Although reversal of AD may not be as rapid with rivastigmine, these characteristics do provide some advantages and may make providers more comfortable with its use.

How will this change my practice?
This small, retrospective study probably won’t significantly change how I approach these cases. Although rivastigmine does seem to be safe for the treatment of AD, I would still likely be discussing administration of antidotal therapy for AD with a toxicologist for recommendations on dosing and to assist the admitting team if the patient does require inpatient treatment.

Editor’s note: Spencer, thanks for pointing this study out to me. Glad to see you’re staying busy with tox consults! ~Clay Smith

Greene SC. Rivastigmine Use in the Treatment of Antimuscarinic Delirium. J Med Toxicol. 2023 Jul;19(3):284-287. doi: 10.1007/s13181-023-00947-1. Epub 2023 May 19.

What are your thoughts?