How do symptoms of agitation manifest differently in disorders such as bipolar disorder, schizophrenia, and dementia, and what challenges does this pose for assessment? What are the most effective pharmacological treatments for acute agitation in psychiatric patients, and how do you determine the best course of action? How do cultural factors influence the approach to managing agitation in various mental health conditions?
Brought to you by the NEI Podcast, The PsychopharmaStahlogy Show tackles the most novel, exciting, and controversial topics in psychopharmacology in a series of themes. This theme is on the “untreatable” dimensions of psychopathology. On Episode 225 on the NEI Podcast, Dr. Andy Cutler interviews Dr. Leslie Citrome and Dr. Stephen Stahl about the clinical difficulties of treating agitation.
Transcript Excerpt from Episode 225:
Dr. Andrew Cutler: Now, does agitation present differently in these different conditions, and how would you go about assessing this?
Dr. Leslie Citrome: Yeah, so that's the age-old question, right? Why are they agitated? Why are they potentially aggressive? Well, it could be someone with schizophrenia. They're acting upon their hallucinations or delusions and that they feel threatened. That's certainly a possibility. Or, you know, it could be that they have some comorbidity that we did not identify. Who knows? They may have a delirium. So the differential diagnosis is pretty long when it comes to agitation, and we need to identify the core source. No matter what the cause is, though, we need to address it.
Dr. Andrew Cutler: Yeah, certainly. And so I would imagine that somebody with dementia, the causes of the agitation, the precipitants could be very different as well.
Dr. Leslie Citrome: Sure. Someone who has cognitive impairment may be agitated because they don't know where they are. They're confused about who the people are that are around them. And frequently, we'll employ some behavioral approaches to their agitation when we can. So making sure there's adequate lighting, making sure that people are oriented with signage and clocks, calendars, and making sure there's no excess clutter in the room, make sure there's no excessive noise. So that goes a long way.
There's a reason in nursing homes why name tags have the name of the function of the person in very large font, such as nurse or doctor or social worker. And that's to orient the person every time they have an encounter with a staff person, so there's less of a chance of confusion. There's also a reason why someone enters the nursing home room saying, Hi, I'm Dan, your nurse for today. Even though Dan the nurse may have been the nurse all month long, every day they have to reintroduce themselves. So those are some of the things that we do to help people maintain a sense of knowing where they are and have a less likelihood of becoming agitated because of fear.
The other thing with dementia in particular is the oppositional behavior that can be present when someone is told to bathe or eat or take their medicine. When someone is confused about the need for bathing, eating or taking medicine. So rejection of care can lead to agitation. And that's often the precipitant for someone ending up in a nursing home.
Dr. Stephen Stahl: Can I ask what the difference is between akathisia, anxiety and agitation? Are these kind of like different aspects of the same thing as you see it, or are they much different from each other?
Dr. Leslie Citrome: Well, Stephen, I'm glad you brought up akathisia because that's often a huge miss on our part that we continually increase the dose of the antipsychotic in the hopes of addressing the agitation when in fact they seem worse. And that's because it's akathisia, which is iatrogenic. You know, akathisia is that feeling of inner restlessness that is uncomfortable and it's manifested physically by pacing about, moving about, being unable to sit still. Unable to sit is, I think in Greek, akathisia. And that can be confused for agitation due to other reasons. And there, the treatment is reduce or eliminate the offending agent.
Dr. Andrew Cutler: Well, Steve, are there common neurobiologic mechanisms here, or common neurobiologic pathways?
Dr. Stephen Stahl: Well, we're just beginning to understand that because we've been treated a little bit more symptomatically and phenomenologically because it's not a diagnosis, it's a dimension of psychopathology that fits with lots of different diagnoses, as Dr. Citrome has already said. But there's interest that certain pharmacologic agents now that either have data or approval seem to help agitation, at least in the dementia sphere.
So rationalizing backwards, you can assume that those neurotransmitters are involved, and they would be things like brexpiprazole, which has been approved, and also the combination of dextromethorphan with other things, whether it be the one marketed compound, approved yet for this, but approved for depression, with bupropion, it's also been studied with some other combinations. Maybe glutamate is involved, and maybe, if you will, some of the neurotransmitters. You could say, because brexpiprazole, for example, is in a group of drugs that you would not give to dementia, right? Except this is paradoxically approved for something for which it's also got a black box warning. I love that.
But what's the property of Brexpiprazole that is doing this? Is it the dopamine, or is it one of those other million different pharmacological things that we have? We've kind of wondered whether that hasn't a little bit more been related to some of the noradinergic alpha-1, alpha-2 properties, rather than some of the other ubiquitous serotonin and dopamine ones. So that's the answer to your question. Maybe alpha-1 noradinergic, alpha-2 noradinergic, and methyldeaspartate glutamate may be involved with the regulation of agitation.