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Optimal BP After Stroke; Psilocybin for Depression

— Also in TTHealthWatch: culprit vessel or complete revascularization?

MedpageToday

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week's topics include eye tracking to diagnose autism, culprit vessel or complete revascularization, optimal blood pressure after stroke, and psilocybin for depression.

Program notes:

0:38 Blood vessel blockage treatment after heart attack

1:38 1,445 patients who had had a heart attack

2:35 On average 5 days hospitalization

3:30 Use of psilocybin for depression

4:30 Two people to accompany

5:31 Medication acts differently

6:30 No serious side effects

7:02 Manage blood pressure after stroke

8:03 Independent functional recovery

9:03 Critical illness physiology

9:20 Eye tracking in autism diagnosis

10:20 Expert diagnosis not 100%

11:20 Most effective biomarker we have now

12:43 End

Transcript:

Elizabeth: Eye tracking to diagnose autism.

Rick: Optimal blood pressure after someone has been treated for a stroke.

Elizabeth: Can psilocybin help with depression?

Rick: In older folks that have a heart attack, do you treat just the vessel causing a heart attack or all of the blood vessels?

Elizabeth: That's what we're talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I'm Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: I'm Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I'm also dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, I'd love to start with the New England Journal of Medicine this week -- this look at, what was a new term for me, the culprit vessel, or all the blood vessels in the heart when you're treating blockages.

Rick: For our listeners that may not be aware, a heart attack is caused when one of the blood vessels that supplies blood to the heart muscle becomes blocked. The treatment for that is to unblock that vessel either using a medicine to dissolve the clot or more commonly, doing a procedure called a percutaneous coronary intervention where you actually go in with a catheter and a stent and open the artery.

In individuals that are over the age of 75, oftentimes they have not only that blood vessel involved, but they have disease in other blood vessels called multivessel coronary artery disease. The question is at the time of the heart attack should you just fix the blood vessel causing the heart attack that's the culprit vessel or should you fix all of them that have a significant stenosis. These are individuals that have multiple comorbidities and are more likely to have a complication during the procedure, so it's not really a slam dunk.

What this study did is it tried to address that. It took 1,445 patients over the age of 75 that had a heart attack. It randomized them to either just treating the culprit vessel or also assessing whether the other blood vessels had a physiologically significant blockage. Then they followed these individuals over the course of the next year.

The individuals that had all the blood vessels corrected were less likely to have either a heart attack, stroke, death, or needing another procedure over the following year. In fact, it decreased from about 21% in the culprit only-treated individuals to about 16%. It decreased the risk of having a heart attack or death by about 36% and the risk of having death alone by 30%. By the way, it would appear to be as safe.

Elizabeth: I'm wondering about how much more time it takes on the part of the intervention team in order to accomplish this goal.

Rick: Elizabeth, it usually can be done within an hour to an hour and a half. Now, these individuals on average spent about 5 days in the hospital. Those that had the complete revascularization were in for an extra day, so a relatively minor inconvenience for what I think are pretty substantial results.

Elizabeth: Yeah. It sounds like a really significant payoff. Now, talk to me about restenosis in those vessels in which stents have been placed.

Rick: It occurs fairly uncommonly. One of the issues is once you put stents in, you put people on antiplatelet agents, and the more intensive blood thinning needs to occur for people to have multiple stents. There was some concern there would be increased bleeding over the 1-year period, but that wasn't the case.

Elizabeth: Sounding to me like this could result in a change in practice.

Rick: You know what, we've known that this is true in individuals that are younger. We haven't known about it in older individuals, but this study actually confirms that it's beneficial in those adults as well.

Elizabeth: Let's turn to JAMA. We're going to spend the rest of our time there. This is a look at the use of psilocybin for treating major depressive disorder. Of course, we've been talking a lot about psilocybin and its utility in lots of different arenas -- things like reducing anxiety relative to cancer prognosis or cigarette smoking, or all sorts of existential issues, if you will. We might be able to consider depression to be kind of an existential issue.

In this study, they looked at the use of it in people who had major depressive disorder with moderate or greater symptom severity. This was in adults 21 to 65 years of age who had had this diagnosis for at least 60 days previous to the study.

The intervention was a 25 mg dose of synthetic psilocybin or a 100 mg dose of niacin. They also employed the whole set and setting, which is of course the preamble to the thing that counseling two people to accompany someone while they're having the experience and then rather extensive support and assessment after the experience.

From a rather large group, they culled 104 participants, and about half and half turned out to get each of these two interventions. Sure enough, they found out that a single use of psilocybin did result in significantly reduced scores relative to things like disability and symptomatology afterwards. That persisted until day 43.

Rick: Let's contrast that with what's routinely done for treating depression. The drugs we use are radically different than the psychedelics. The current drugs actually suppress depressive symptoms. They do that by targeting the presumptive underlying biological dysregulation -- things like serotonin and tryptamine, and they have to be taken over a long period of time to be effective, and in some individuals are not.

What you just described is a medication that acts differently. It doesn't actually suppress depressive symptoms, but it tries to enhance the experience so people know how to deal with them. It does involve intensive psychotherapy. It involves individuals that know how to help the individual with the single dose and how to interpret and to deal with the experiences that occur at the same time.

Elizabeth: I think, of course, it's important to talk about the adverse events, because a majority of the participants in this study, both the control arm and the psilocybin arm, reported at least one adverse event through day 43. These are kind of adverse events writ large. They are not things that are life threatening that's going to get somebody hospitalized. But certainly in somebody who is already having mental health issues, they could exacerbate that.

Rick: Right. That's why it's important to have somebody there that is familiar with this and could help usher the person through the experience. As you mentioned, the side effects weren't serious. There were concerned that this could actually increase suicidal ideation or behavior. That did not occur in any of the patients. The side effects just occurred around the time the drug was administered.

Elizabeth: Finally, let's note that the editorialist says that there are a significant number of patients who do not respond to this therapy, so it's not a panacea.

Rick: No, and in fact it's not ready for prime time. It will still be used in clinical trials so we understand a little bit more about proper dosing, but more importantly, who is most likely to respond.

Elizabeth: Staying in JAMA.

Rick: Elizabeth, let's talk about treatment of stroke and how you manage blood pressure afterwards. Oftentimes, these people have elevated blood pressure, and the question is what's the most appropriate blood pressure to help spur continued recovery of neurologic function. The current recommendations is to keep blood pressure below 180 to 185 systolic.

There were two studies published back to back that looked at the benefit or potential benefit or harms of using a lower blood pressure target. The thought being is that the higher the blood pressure, the more likely one is to have bleeding after a stroke. There actually may need to be an increased blood pressure to provide blood flow into the brain that's swollen.

The first of these studies, in South Korea, in which the target was to enroll 668 patients to either target a blood pressure of 180 or about 140, the trial was actually stopped halfway through because what they discovered is there was actually more harm with the intensive blood pressure lowering. Those individuals that followed the recommendation, their chance of having an independent functional recovery was 54%. Those in whom they lower the blood pressure to about 140, it was only about 39%.

The other trial, also reported in JAMA, looked at blood pressures of 140, 160, or 180 and determined that lowering the blood pressure to 140 or 160 was unlikely to provide any benefit and was more likely to provide harm.

Elizabeth: This whole issue of blood pressure, and especially blood pressure in critical illness, we've certainly spent a lot of time talking about this. There must be some compensatory mechanism for increasing blood pressure under those circumstances that's actually beneficial.

Rick: Elizabeth, I couldn't have said it better. In the setting of a stroke where there is swelling or edema in the brain, if you don't maintain a high blood pressure, you don't get adequate blood flow to the other areas of the brain that are potentially at risk.

Elizabeth: It adds also, as far as I'm concerned, to this body of knowledge emerging about critical illness. That's really a category that's separate and that has a different physiology.

Rick: Absolutely. That's why these four studies are particularly important.

Elizabeth: Our final one this week, again in JAMA, looking at eye tracking measurement of social visual engagement compared with an expert clinical diagnosis of autism. I'm reminded in this study of the rather daunting statistic that 1 in 36 kids in the United States have autism, or let's call it autism spectrum disorder because as we know there is a wide range that's represented here.

This study took a look at 16- to 30-month old children enrolled at six U.S. specialty centers to look and see whether this eye-tracking software would arrive at the same place that an expert clinician would arrive at in diagnosing autism. They were successful in employing the software in 475 of 499 enrolled children in these centers. They also had a wide range, happily, of ethnicities who were represented in this study. They found out that this software does actually correlate pretty well with the expert diagnosis.

The editorialist points out that expert diagnosis too with regard to sensitivity and specificity is not 100%. So it's comparing pretty well. It could be very accretive to the diagnosis of autism spectrum disorder, which is so important in terms of intervention.

Rick: Making the diagnosis of autism can sometimes be very difficult for experienced clinicians. The autism is actually characterized by decreased spontaneous visual attention to social stimuli. Apparently, this occurs very early in life. Kids are on different areas of the autism spectrum. Children that have very high cognitive function or language abilities that have mild autism are often likely to be missed early on. The earlier that we can start treatment, the more effective it is in terms of kids dealing with these symptoms.

Even when experienced clinicians evaluate individuals that are suspected of autism, a third of the time, they're just not sure. You'd like to have some sort of a biomarker, and what you described is having these kids watch the videos. Eye tracking can in fact be probably the most effective biomarker we have at this particular time.

The technology for this is pretty simple. It takes an hour of training to figure out how to do it. There are a lot of good things about this. Now, should it be rolled out for screening? We don't have enough information. The sensitivity and specificity will change, because the group that this studied were individuals that were suspected of having autism. But if you take the general population, the sensitivity and specificity will be different.

Elizabeth: Let's just put some numbers on it. This eye-tracking test was able to accurately classify autism versus non-autism in children with 71% sensitivity and almost 81% specificity, with a positive predictive value of 76.2. We got a little wiggle room in here.

Rick: If you take a look at those individuals that were shown to have autism, the specificity goes up to 85% and the sensitivity is almost 80% as well. Does it provide additional information? Absolutely. Is it easy to do? Yep, and I think we're going to be figuring out how best to use this in terms of either screening or confirming.

Elizabeth: I absolutely agree. On that note then, that's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.

Rick: I'm Rick Lange. Y'all listen up and make healthy choices.