In this Q&A session from Neurology Week, Joohi Jimenez-Shahed, MD, medical director, Movement Disorders Neuromodulation and Brain Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, and Rajeev Kumar, MD, FRCPC, director, Rocky Mountain Movement Disorders Center, Huntington’s Disease Society of America Center of Excellence, Colorado Neurological Institute, Englewood, CO, answer questions about treatment options for Tardive Dyskinesia (TD) and its impacts on quality of life.

Dr Kumar and Dr Jimenez-Shahed spoke at Neurology Week 2021 on “Tardive Dyskinesia Across the Complexity Spectrum – From Quality of Life Improvement to Novel Treatments.”

Read the Transcript:

Dr Jimenez-Shahed: Dr Kumar, thank you so much for that presentation, and I think we did that split, so it was a nice initial introduction to tardive dyskinesia and then the actual treatment.

Our first question from the audience is actually about haloperidol because that drug has been around for a while. Is that the type of medication at this point that is considered to be too risky to be in regular use, or how do you view that medication, especially in the framework of tardive dyskinesia?

Dr Kumar: It depends on why you're using it. Haloperidol is a very strong D2 receptor antagonist. It's a classic D2 receptor antagonist. It's a great medication when used at the right time for the right patient.

If you have a patient who has refractory psychosis that is not responding well to other D2 receptor blockers, starting with atypicals, for example, and then they need atypical, let's say, tizanidine, for example, and that is still not strong enough, haloperidol is the strongest.

There's no reason one can't use it, but all of the atypical antipsychotics, the stronger the D2 receptor blocker is, the higher risks of tardive dyskinesia. You should use it when it's indicated, but you should be warning your patient about the risks of using it.

Dr Jimenez-Shahed: That's one of the challenges with the landscape of dopamine receptor blocking use at this point.

There's certainly conditions where they're indicated and they're appropriate for usage, but it's just having that conversation with patients about what these medications are and what some of the potential long-term consequences are so that patients are informed and that you know that you need to be watching for these things as the treatment continues for these patients.

Dr Kumar: No, absolutely. I think that, of course, as you use a stronger D2 receptor blocker, the frequency of screening for the emergence of tardive dyskinesia then needs to be increased for sure.

Dr Jimenez-Shahed: Yeah, absolutely. That's a great habit to get into so that you can catch this as it's starting, and hopefully take appropriate action. What tips do you have -- I know this is partly my section still, but I'm going to let you try to take the first stab at answering -- but what tips do you have to differentiate an atypical tardive dyskinesia from a functional disorder?

That's a very interesting question and actually an important one because patients may come in with all different kinds of movements. What are some of the features that might suggest that it's organic versus functional?

Dr Kumar: The first things are to look at the classic things that might lead you towards thinking about a functional movement disorder such as abrupt onset, such as the coexistence of non-organic or non-physiologic finding, distractibility, entrainment, response to suggestion of placebo, and variability, of course.

All of these things would lead you to believe that the disorder may be functional. Now, there are certain characteristics of tardive dyskinesia which are helpful. For example, it'd be very uncommon to have somebody who has tardive dyskinesia who doesn't have involvement of the face also.

If you have only limb involvement, trunk involvement, it's not a predominant dystonic syndrome, it's truly choreic, and you have zero involvement with the face, lips, tongue, it'd be very unusual, and you got to be thinking this is probably not tardive dyskinesia.

Tardive dyskinesia is usually worsened during certain activations, especially, for example, in the face. If you have the patient perform rapid eye movements with the hands, it commonly worsens or brings out, so there's a worsening. If you see the opposite if they're distracted, that should make you think this may be a functional disorder. Those are some simple tips. Please, I'm sure you'll have other good ideas.

Dr Jimenez-Shahed: I think that those are all really good points. Probably the time course is one of the single most important things and trying to figure out what's going on with the patient.

Just remember as we talked about and presented that there are acute movement disorders that can happen after patients are exposed to a dopamine receptor blocking drug, there are things that are maybe in that intermediate-range that maybe come in weeks after, and then there's the things that are truly latent. You do have to have this high index of suspicion.

First of all, you have to know to ask for the exposure. Then secondly, you have to establish what the relationship is between the onset of that exposure and the onset of the movement disorder. Then, as Dr. Kumar mentioned, all of these different other clinical features and historical features that can help you decide whether it's functional or not.

More than anything, tardive dyskinesia is consistent. It's patterned. You're likely to see it in the same pattern under usual, and even sometimes some distraction maneuvers that we might do.

If you're seeing that same pattern happening over and over again, especially if it fits one of those phenotypes that we talked about, then you should definitely have that index of suspicion. Definitely a good question.

Another one, let's go to, another audience member asked, "Does new onset of tardive dyskinesia result in any impact on cognition or intellectual ability? Is there any kind of relationship there?"

Dr Kumar: That's kind of a complicated question. We know that there's an association if we look at all patients who have, for example, the same psychiatric disorder, let's say bipolar or schizophrenia, comparing those people who have tardive dyskinesia and those people who don't. We know that if you do comparative studies, that patients who have tardive dyskinesia tend to be worse cognitively.

Some of that may be due to the underlying psychiatric disease. Some of that may be due to their relative to drug refractoriness too because, of course, the patients who tend to get tardive dyskinesia are the patients who've been on higher doses for longer, have different antipsychotics. If a patient is doing relatively well, they're less likely to get tardive dyskinesia.

The other issue is, of course, something of a artifact of testing. If you have bad tardive dyskinesia, that may be quite distracting. If your attentiveness is reduced, that's going to have a downstream effect on any cognitive testing that you do working memory tasks.

If I'm distracted because I'm moving all over the place, it's going to impact my performance. That's another issue. Then, of course, if you're having tardive dyskinesia that can have a secondary effect on mood, and if I'm down in the dumps, people who are depressed obviously perform poorly on cognitive testing. That's another issue.

Dr Jimenez-Shahed:  Those are all very good points. Maybe as a marker of disease progression or anything, I don't know that we necessarily think of it in that sense. It's mainly just a manifestation of the treatments and the interaction between the medicines that are used to manage psychiatric condition and the control of movement.

Slightly, I think another interesting point to note about the population of patients that we're dealing with. It's great that these medications are out here. We've got a couple of FDA-approved options, how do patients get access to these medications?

Dr Kumar:  First of all, we can prescribe the medications either to a regular pharmacy or a specialty pharmacy, depending on the medication, depending on the patient's insurance, and depending on caregiver issue. We have a lot of different options.

Perhaps the biggest issue with respect to access is cost also. These are very expensive medications. If one were to self-pay, very few patients could afford them. The good news is that for most patients, these are covered medications because they're indicated.

As long as you have a proper diagnosis, you're prescribing on label. They're generally covered by most state Medicaid plans. That is also good because a large number of these patients, of course, have been terribly affected financially, and they're often on Medicaid. So that is good.

For patients who are not on Medicaid but they do have commercial insurance, for example, and we just write it to a regular pharmacy, a specialty pharmacy, depending on our choice and what's appropriate in our institution, then they can often...

A vast majority of patients qualify for patient assistance programs. It's a very small number of patients who don't. For both Deutetrabenazine and Valbenazine, that is the case. I would say it's a rare patient who can't get on medication for that respect.

Then lastly, you've got the Medicare population, which is a little bit complicated because patient assistance programs are more difficult to access. Depending on the patient's insurance and depending on how well you can get the patients hooked up with the foundation, again, most patients can get access to medication at an affordable price through subsidization through foundations.

There's a lot of hoops sometimes to go through. What's good is that typically for the patients who are not on Medicaid, for example, etc., by accessing some of the hub support systems through the different manufacturers, they can usually help the patient get on one patient assistance program or the other in the vast majority of cases.

Dr Jimenez-Shahed:  Thank you for that explanation. I think that these medicines are not restricted to use by neurologists or psychiatrists.

If you're a primary care or other practitioner who recognizes this phenomenology and you feel strongly that the patient needs to be treated, or perhaps you're assuming the care of somebody who is being chronically treated with these conditions, there's many different ways to access the medication and so I agree with what Dr. Kumar described.

That when we're using it on label like that, it's often quite available and patients who really need it can get access to them. That's definitely a good part of this that has emerged in the last couple of years, that these drugs have become available.

 Joohi Jimenez-Shahed, MD, is the medical director of Movement Disorders Neuromodulation and Brain Circuit Therapeutics at Icahn School of Medicine at Mount Sinai in New York, NY. Dr Jimenez-Shahed received a medical degree from Baylor College of medicine and completed a residency in Neurology at the Duke University Medical Center. She is the recipient of the Roy H. Cullen Quality of Life Award (Houston Area Parkinson Society), the Rising Start Clinician Award (BCM), the Fulbright & Jaworski L.L.P. Faculty Excellence Award in Teaching and Evaluation (BCM) and the Healthcare Heroes Award for Outstanding Health Care Practitioner (Houston Business Journal).

Rajeev Kumar, MD, FRCPC is the director of the Rocky Mountain Movement Disorders Center and the Huntington’s Disease Society of America Center of Excellence at the Colorado Neurological Institute in Englewood, CO. He attended medical school at the University of Saskatchewan in Canada and completed a residency at the Mayo Clinic. Dr Kumar is involved in clinical trials in Parkinson’s disease and Huntington’s Disease.