Brandon Jakubowski, MD - phaware® interview 542

Oct 15, 2025

Treating Meth-Associated PAH Without Judgment

Dr. Brandon Jakubowski takes us into the underrecognized world of stimulant-induced pulmonary arterial hypertension. From misdiagnoses to under-prescribing life-saving therapies, he lays out the systemic gaps and stigmas preventing patients from getting the care they need.

This Special Edition Episode Sponsored by:  Johnson & Johnson

My name is Brandon Jakubowski. I'm an Assistant Professor of Internal Medicine at the University of Texas at Southwestern Medical Center here in Dallas, Texas. Ever since med school, I was actually interested in pulmonary hypertension. I remember seeing my first pulmonary hypertension patient as a third year medical student. It was on the pediatrics rotation, actually. Everyone told me, "There's this patient in this room on this continuous IV infusion. If it falls out, it's really scary. Be there immediately to help the nursing staff." At the time I thought to myself, "What on earth is this disease?"

Just through kind of sheer luck and happenstance, I got put on the pulmonary hypertension unit when I was a fourth year medical student, and I just fell in love with the physiology. I fell in love with the patients. I knew I wanted to dedicate my life to it. It's a disease process that if you look at the last 20 years, the amount of therapies that we have had just exponentially increased. I'm super eager to see where the next 20 years leads us.

So today, I'll discuss a little bit about the historical perspectives of drug and toxin-induced pulmonary hypertension. I really want to emphasize on some of the challenges in this space, particularly access to advanced therapies and under recognition and stigmatization of drug and toxin-induced pulmonary arterial hypertension.

For us as PH physicians, it was kind of in the early 2000s that we started to have increasing recognition that stimulant use was associated with pulmonary hypertension. That was really based primarily on small case reports. It wasn't until 2006 that the Center at UC San Diego published this groundbreaking article. Essentially what they found was, patients that were labeled as idiopathic pulmonary arterial hypertension, about 25% of them actually had a history of stimulant usage. When they compared it to other associated forms of pulmonary arterial hypertension that had known risk factors or had known chronic thromboembolic pulmonary hypertension, they found that there was a pretty stark difference. Only about 4% of those patients actually had a history of stimulant usage. That's really when we started to think, "Wow, this might be a definite association." Now, it should be kind of routinely part of our screening process, because we know that untreated stimulant usage or continued stimulant usage only leads to worsening pulmonary hypertension and worsening RV failure.

I think the inception of the field of pulmonary hypertension is really the most fascinating one. It really started in the early '60s when there was this epidemic of weight loss medication called Aminorex that was available over the counter. One German scientist, actually, saw that he was diagnosing a lot of, what they called at the time, primary pulmonary hypertension in his own cath lab. As astute as he was, he was asking them their histories and drug histories and found out that the large majority of them are actually taking this weight loss supplement.

It was over the course of the next several years that more reports of this were coming out of Austria, Germany, the surrounding area, and that actually led to the medication being taken off the market in the early '70s. The thing that's fascinating about it is, if you look at the chemical structure of Aminorex, it's very similar to the chemical structure of fenfluramine, a weight loss medication, that was commonly prescribed here in the United States in the '80s and early '90s, and also very chemically similar to methamphetamine, amphetamine derivatives that people use nowadays.

I think this was a really big mistake by the medical community and by the FDA, not recognizing that Fen-phen had a definite association with pulmonary arterial hypertension. It was on the market for 16 years ultimately, whereas Aminorex was on the market only for maybe 4 or 5 years in total after its recognition. I think there was just a really large appetite for people to have access to these weight loss therapies at the time. Even, I believe, it was the CDC put out a statement that said, "The risks and benefits of untreated weight loss may be worth it if you have to take the risk of being on this medication, potentially, that can lower people's weight." But I think in my opinion, big mistake. Really did not do justice for our patients or the medical community.

There's a definite geographic trend of amphetamine usage in the United States where the West and the Midwest are dominated by much higher rates of methamphetamine usage compared to the East Coast. But the statistics are actually quite alarming. It's about one and a half million Americans that report methamphetamine usage in the last year, and about a hundred thousand of those actually tried methamphetamine for the first time in that year. We're starting to see increasing rates of overlap between drug use with patients using cocaine and methamphetamines or opiates and methamphetamines.

Some of the really concerning thing is, you look at just US 12th graders, 1.1% of them have reported using methamphetamine in the last year, too. I just think those are statistics that are kind of shocking to the mind, and it's something that we need to routinely screen for. I think people so often are worried about or trying to hide their drug use for fear of negative judgment or embarrassment or even risk of legal consequences, and that leads us to misdiagnosing them, ultimately.

It's really difficult, on occasion. You want to be able to ask these questions in a very non-prodding manner, in a non-judgmental manner. It's usually a question that I'm saving for later in my conversation with patients. The way I like to frame it is, "These are a set of questions I ask all of my patients, and they're not meant to be judgmental. They're meant to make sure that we have an understanding as to what your disease process is." I start with things like, "Have you been tested for sleep apnea? Do you have symptoms of sleep apnea?" Before moving into what people think may be more some of those prodding questions like history of illicit substance use. But I find that waiting till later in the visit at the point in time where I've been able to establish rapport with a patient and gain their trust makes them much more likely to want to divest that information to me.

I often tell patients that there's a set list of things that we know cause pulmonary hypertension, and this is at the point in time that I'm explaining to them the pathophysiology and how pulmonary hypertension progresses over the course of time. I like to tell them that if we can identify a cause of what's leading to pulmonary hypertension, we should treat that underlying cause, ultimately. If that's from chronic blood clots in the lungs or if that's from an underlying autoimmune disorder, anything that we can do to minimize the risk of PH progressing, we should undertake that.

That's no different for stimulant-associated PH. I think one of the key ways of getting this information from people is just being honest, saying, "A significant portion of patients in our clinic report some history of methamphetamine usage. And I'm curious, have you ever used methamphetamines in your life?" It's really coming from that question in a manner of curiosity and understanding as opposed to an accusatory nature.

Sometimes, people do not want to tell you this information. Again, that's because of fear. I think fear of the unknown, fear of legal risks, fear of being stigmatized or fear of being treated differently because of their history of drug use. But again, I think that's why it's so important to focus on developing rapport in the first 30, 40 minutes of your discussion with somebody, really sitting there and listening to how have their symptoms progressed over time? What are they dealing with now currently? That way, they can feel like you are an ally in their healthcare, working towards getting them better, ultimately.

It's unfortunate that despite the life-saving potential of parenteral prostacyclins, these therapies are notoriously underutilized in clinical practice. This is true for our idiopathic PH patients, and this is especially true for stimulant-associated PH patients. Really, our guidelines say that any high-risk PH patients should be started on IV or subcutaneous prostacyclin in addition to oral therapy. Though the reality is that most patients that meet this criteria, never receive a parenteral prostacyclin. We have decent national registry data from the PHAR registry that reveal a pretty striking gap in patients that have stimulant-associated PH and that they're far less likely to be on IV prostacyclins compared to their idiopathic counterparts.

It's only about 6% of stimulant-associated patients get IV therapy as opposed to 28% of idiopathic patients. That's adjusting for lots of factors. You see that stimulant-associated PH patients have an overall lower odds ratio of about 90% to get onto IV therapy. I think that just confirms that clinicians are very hesitant to initiate this aggressive therapy in this patient population. That's due to concerns about adherence and instability or active drug use. But the unfortunate consequence of that is that many of these patients are under-prescribed, despite the severity of their disease and only managed with oral medications that are unlikely to really control their disease in the long term.

We have an incredible experience treating this patient population at UT Southwestern. I found that with our multidisciplinary approach we are able to utilize resources from our psychiatry colleagues and deliver compassionate care and substance abuse counseling. These patients can have dramatic responses not only to PAH therapy, but just to cessation of their drug use.

We see rapid improvement in right heart function with cessation of methamphetamines. Again, this gets back to the point of why it's so important to recognize this early on, because I've seen patients who initially were diagnosed as idiopathic pulmonary arterial hypertension, and it wasn't uncovered until maybe a year or two years later that they actually had a history of active substance abuse, and it was only recognized in the workup going into transplant or things of that nature. That's something we want to avoid if we can, because we want people who are, despite sliding of their medical problems on therapy, we want them to be able to get transplanted. We have our own several success stories at UT Southwestern of patients who were previously abusing methamphetamines and are now transplanted and doing really well.

There's a huge research gap in this field. I really applaud the clinicians out of Stanford for doing a majority of the work in this space. But there's no doubt there are definite challenges in this patient population with the comorbidities and concerns for active drug use. I think it's so incredibly important to have avenues for support for them. That way we can ensure that they're adhering to therapy and deriving the benefit that we see in other patient populations that have PAH. Historically, these patients have been excluded from clinical trials with active drug use. That's understandable in order to get a best quality sample ultimately for clinical trials.

But we need to really, as a whole, the medical community needs to build a better rapport with this patient population. These patients have been stigmatized for so long that they don't want to seek healthcare because of concern of being treated unfairly or being treated improperly. So, we need to do a better job of categorizing and being able to follow these patients long-term with registry data and even with clinical trial data.

Essentially, many patients, not just those with stimulant-associated PAH, but even those with other forms of pulmonary hypertension suffer from a lack of access to care at specialized PH centers. This is for a variety of reasons. Sometimes, there's not a specialized PH center located near them. Sometimes, they come from very underserved communities with very limited access to healthcare resources. That's unfortunate, because we know that stimulant usage is highest in lower income communities or communities that don't have the same educational resources that others do.

You add on top of this, things like the socioeconomic obstacles and under-insurance, lack of transportation, all of these things make a consistent follow-up and treatment in this patient population particularly difficult. So, it's something that, as a healthcare community, we have to continue to focus on to better the lives for this patient population.

Thanks for listening. My name is Brandon Jakubowski, and I'm aware that my patients are rare.

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