This Physician Realizes He Might Have The Movement Disorder He's Been Researching.

I've been developing AI identification algorithms for tardive dyskinesia, all while missing the fact that I might have tardive dyskinesia myself.

The Frontier Psychiatrists is a daily enough health themed newsletter. Today's article I put off. I knew I had to write it, but didn't want to. I have to make an appointment with the doctor. I have to have a conversation with the rest of my team, including the brilliant Anthony Sterns, Ph.D., at iRxReminder. I need to chat with Loren Larsen at Videra Health.

I'm sure I'm not going be able to stop talking about this for years. Oh, the irony! OK, time to stop procrastinating.

I've written previously about having bipolar disorder. For many years, I took a series of medications called antipsychotics. These drugs blocked dopamine, and for many years were a mainstay of treatment for bipolar disorder. Just last week, the treatment guidelines were updated to emphasize using lithium first line—a medicine that may need to be started earlier than the course of illness to work. I got lithium at least 20 years into my disorder, and it wasn't particularly helpful or tolerable for me. It’s better for many, though, and I even co-authored a publication on the topic last month in Bipolar Disorders. Eventually, I was able to discontinue, in keeping with my doctor’s judgment, the dopamine blocking medications.

I've been off of this class of medication for several years now. I have written before about the burden of weight gain from a psychotic medications—a side effect I experienced.

I've lost a lot of weight thanks too appropriate medical care. I'm happy about that. And hey, at least I don't have a permanent movement disorder which is the other side effect of antipsychotic medications that you take for many years.

Except, maybe I do?

I've been having this need to move my mouth. I've talked to my doctor about it. I thought I had perhaps…some sores in my mouth from my autoimmune disease. I do have some of that from time to time. When it really felt like I had to smack my lips, and my doctor looked inside, she didn't see any obvious sores. That's weird. My wife has mentioned it on a couple of occasions. So did my mom.

“Why are you doing that weird thing with your mouth?”

She thought it was an affectation.

I'm beginning to think she was really did notice something, but it's not a…voluntary…movement. And movement disorders are all about involuntary movements. When you have an involuntary movement, you notice you are moving. You kind of can't help but notice it. But you're not automatically gifted, from on high, by the gods, with the knowledge of why you are moving. The real answer is you have a movement disorder, there's output from your brain, and it tells your muscles to move, and they move, and none of that is under voluntary control.

There are a variety of movement disorders in the world, there's a whole subspecialty of neurology dedicated to this. One of the ways I explain the psychiatric problems my patients have is by equating them to a movement disorder but of feelings.

What are movement disorders? We have dystonia, which is involuntary contractions of muscle across both sides with a joint. There are tic disorders, where you get an uncomfortable sensation, and eventually you have to move. There are dyskinesis, where you have to move around in ways you weren't planning to move around, but that's just what's happening.

Tardive dyskinesia is a late developing movement disorder. Dyskinesias are seen in Parkinson's disease, quite frequently. They are also seen in people who have been given antipsychotic medication's for many years. This is particularly true of the older class of medication's like Thorazine, Haldol, and the like, this late developing movement disorder called tardive dyskinesia was a common and disabling side effect.

It happened only after many years of taking the medication for some people, and for others that happen more quickly. The rate is about 4% per year with those older medications. When clozapine came along, it was a big deal, because it didn't cause any movement disorders, and it still treated psychosis. It treated psychosis better than anything else. An entire generation of medications was developed on this model, which we called second generation antipsychotics. As I've written about extensively in my book inessential pharmacology, none of them worked quite as well as clozapine. And all of them caused this movement disorder that clozapine bypassed. It was at lower rates, around 2% per year, but over many years of taking a second generation antipsychotic, the risk of developing tardive dyskinesia (TD) is still about 20%, if you take the drug long enough.

So here's the nasty part—the drug you're taking, that blocked dopamine? It both causes TD, but it also masks TD at the same time. Dyskinesia are caused by too much dopamine sensitivity in a movement circuit. The antipsychotic drugs are both up-regulating the sensitivity to dopamine in that circuit, and it's blocking it at the same time. The reason this is particularly nasty is the drug is causing, for many years, a movement disorder. But while you're continuing to take the drug, you can never see how bad the movement disorder is going to be when you stop the drug. At which point, the masking effect of the drug is gone, and you see the full impact of the movement disorder you've developed while taking a drug for many years. As soon as you notice the movement disorder, it's too late. Or at least, it was too late. Recently, medications have been developed that can treat this adverse effect. These are through medication according to the FDA, and they include tetrabenazine and valbenazine. These are obviously drugs for a side effect caused by antipsychotic medications, and it's nice to think that those are only going to impact people who have disorders you don't have. They're going to impact people with bad illnesses like schizophrenia, which most good people don't have—I'm being sarcastic here.

On the whole, most people don't have schizophrenia. Only about one percent of people have that illness. It doesn't make you a bad person, but it is easy to imagine that if you don't have schizophrenia, you're not gonna get a side effect from medication that is traditionally associated with its treatment. Even if you end up taking that medication for something that you have, or something that's pretty normal, like depression, or bipolar disorder. Things that are common.

To give you a sense of how common in the prescribing of these medicines are, Abilify, the trade name for the drug aripiprazole, was, at one point, the best selling drug on earth. It made Otsuka $6.9 billion a year at its peak. These are blockbuster drugs. The drug makers realize that they didn't just work for psychosis, they would actually augment oral antidepressants and get a little more efficacy out of drugs that weren't doing the trick. So for people who had bad depression, or bad bipolar depression, it was very common—is very common—to have augmentation with antipsychotic medications be utilized. Although plenty of people take a pill for schizophrenia, many, many more people take it for depression.

And that class of drugs that was being used to augment oral antidepressants that didn't work well enough? That whole class medications, at around 2% per year, capping out at 20% over a lifetime, can cause a permanent movement disorder.

Usually, tardive dyskinesia shows up in the face. It looks like movements of the mouth, tongue, blinking, but it can cause involuntary movements of the fingers, toes, torso, and can be quite severe.

I was taught this in school. But I didn't learn to fear it. I didn't learn to distrust these medicines. In residency, you learned to prescribe these medicines, and to council patients on the risks. But again, there's a quirk of the amount of time you're spending in residency, because it's limited. You prescribe a patient a medicine for the first time, and, if you're taught well, you're taught to describe the risks, and then you're never going to see that patient again. Or you'll see them for a year, and that's it. And then you graduate, and then you get a job. In that job, you'll probably see patients for a couple years, and then you'll get another job. You don't get to see the whole story. You don't get to see someone for whom you prescribe a medicine, and then 15 years later, watch that same person develop a permanent movement disorder that was from the drug that you initially prescribed. If you're lucky, you learn to screen for tardive dyskinesia really well, and you identify it happening in one of your patients before it becomes severe, and you take the appropriate steps—you switch the patient to clozapine, you make a referral to movement disorder specialist, etc.

What most probably don't do is become obsessed with this problem, and spend years trying to address it. That's what I've done. Back in 2020, I got to know someone named Dr. Anthony Sterns, who I still work with today. He's a psychologist, and a good friend. He had an idea—he had been working with colleagues at a company called Videra Health, and we're pretty sure we could put together some of his technology, an Internet-of-things connected dispenser and smart-phone application to track antipsychotic dispensing, and combine it with the video capture technology that Videra had built, to assess and screen for the risk of tardive dyskinesia. We met on Clubhouse originally, and then met again in the What If Ventures accelerator, and he talked me into working together. We work together to this day. I love working with Anthony. I even talked my wife into being a rater on the clinical trial we were working on, where we evaluated hundreds of videos of individuals taking an antipsychotic medications, to determine if they had tardive dyskinesia. We then trained an algorithm on that data, and that algorithm performed remarkably well. I can't even tell you how well yet, because it hasn't been published yet. It should be available shortly.

It's a really good algorithm. The sensitivity and specificity are better than any human study of screening for a tardive dyskinesia has ever done. It's a nice contribution to science. If you're interested in that tool, and you're a psychiatrist, it's actually available right now, right here:

TDscreen.ai

You can use it with your patients to screen for the very disorder I'm writing about right now. I spent thousands of hours on this project, and we have really exciting tool to identify an adverse effect. There is one person, however, I never used that tool on…

You remember, above, I told you I stopped taking an antipsychotic medications years ago. I'm lucky to not need them anymore. The weight gain has been addressed— thank God for modern medicine.

I also told you I have this weird mouth movement. And I do. And I realized, while talking to Dr. Sterns earlier today, and editing a paper last night, before the first paper is even finished by the way, then I might have TD also.

I have this weird mouth movement. I didn't used to have it. It's not voluntary. People notice it. I'm noticing it. It feels a little uncomfortable. Something Anthony said in a meeting, earlier today, really brought it home for me. The drugs mask the side effect. After you stop taking the drugs, that's when you might see it. For some people. And that's when I started having the problem, this weird movement of my mouth. After.

I have to go see a movement disorders doctor, myself. And maybe, these new medication's have written about it will be really helpful. I'll get write about that too.

I was passionate about helping people avoid this problem before. I'm likely to become more ardent, still. I am very lucky, I want to make that clear, the medication's were stopped for me because I didn't need them anymore. Before anyone could see the side effect. I had it, but it was masked, and it was so mild it wasn't there to see. It was not particularly distressing or disabling. The medications were discontinued before I even knew I had this adverse effect. That's better news than most people get. I am grateful, and lucky. Other people, however, even more vulnerable people, are not that lucky.

We need to get better at screening for TD. Conveniently, along with my colleagues, I actually built a tool to make that easier to do. Before I even knew I might have the problem! It doesn't look like much in this video, my wife promises me there are more videos on TikTok where you can see it more prominently.

I'm gonna go from being a doctor to being a patient, and I will probably write about it, too. None of us are immune to the bad things that can happen when we don't do the best possible math on the risks that we’re undertaking. It's probably better to not just consent people to risks that happen dozens of years later, but to relentlessly try to reduce the risks to which people are exposed. Especially vulnerable people. This is why I'm such an enthusiast for brain stimulation. Treatments like TMS have decades of data suggesting their safety profile is excellent. We deserve better options, hands-down, for depression than permanent movement disorders. Better options than severe weight gain.

That's why I'm excited about medicines like Cobenfy—the very first novel and psychotic that doesn't cause weight gain—and doesn't cause movement disorders, and that's available for people with psychosis now. When we have a suspicion that there's something we could do better, as physicians, something that could be safer, something that should get to more people, it is incumbent us to do that. It’s a responsibility to do everything we can to bring that better and safer option to the world. Nothing is perfectly safe—especially when we're facing the spectre of illnesses that ruin the lives of people struggling with them. Treatment will have risks. However, if we can do better, if we can use something dramatically safer, we very much should. We shouldn't stop advocating until that more effective and safer treatment is the standard, everywhere.

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