Advancements in Tardive Dyskinesia Understanding and Management

Psych Congress Network caught up with Craig Chepke, MD, DFAPA, who is the scientific advisor and a steering committee member of Psych Congress, while on-site at Psych Congress 2023 to discuss the latest advancements in the understanding of tardive dyskinesia and how clinicians can adapt their assessment and management strategies with this new knowledge.

Dr Chepke, also the medical director of Excel Psychiatric Associates, encourages clinicians to properly address if the patient is experiencing impact from TD symptoms and explore the implementation of the 2 FDA-approved treatments for the disorder.

For more expert insights on effectively treating tardive dyskinesia, visit our Tardive Dyskinesia Excellence Forum.

Visit our newsroom to catch up on more insights from Psych Congress 2023.

Hi, I'm Dr Craig Chepke. I'm the Medical Director of Excel Psychiatric Associates in Huntersville, North Carolina, an adjunct associate professor of psychiatry for Atrium Health, and a Steering Committee member and scientific advisor for Psych Congress.

Question: Can you provide an overview of the latest advancements in the understanding of tardive dyskinesia and pathophysiology? How should clinicians adapt their assessment and management strategies based on these advancements?

Dr Craig Chepke: Tardive dyskinesia is one of the most vexing problems we have faced in psychiatry for over 70 years—most of which we've had no treatments for it. But, in the past six 6, we have had 2 FDA approved treatments, and we've got to change our management strategies and assessment strategies because of that.

We've known for some time that the pathophysiology of tardive dyskinesia may involve upregulation of post-synaptic dopamine 2 receptors, but we have to amend that a little bit, and it's a little bit more complicated than that, as I like to say. So, it is still the case where we do believe that there is an upregulation of the post-synaptic D2 receptors. When you block the dopamine receptors for too long, some people who are genetically susceptible, do get the upregulation of the oversensitive dopamine receptors in the nigrostriatal pathway, the motor pathway, and that is part of what leads to tardive dyskinesia.

We also have to consider that there's an imbalance in the dopamine signaling and the cholinergic signaling because if we just think about the dopamine signaling and we forget about the cholinergic signaling, that's how things happen, like having people on anticholinergics with tardive dyskinesia, which is very rampant and actually worsens TD. It says that in the package insert of some of the most commonly used anticholinergics. Those treatments, like Benztropine, are best reserved for people with drug-induced parkinsonism and/or drug-induced dystonia. But even then, there could be better treatments.

Amantadine can be better for drug-induced Parkinsonism. Botulinum toxin injections, for some people with dystonia, can be better; and taking people off of the anticholinergics—slowly though. We don't want to pull people directly off. They can get a cholinergic rebound, not dangerous, but they feel terrible. So, that's how we would want to prepare the way for people—removing anticholinergics that are unnecessary.

Ultimately, the treatment for tardive dyskinesia is the 2 FDA-approved VMAT2 inhibitors. VMAT2 stands for vesicular monoamine transporter type 2. It's what concentrates the dopamine, as well as other monoamines, but we're going to focus on dopamine, into the presynaptic vesicles, which allows it then to be released into the synapse. If we reduce the amount of dopamine in the vesicles by blocking VMAT2 with one of these 2 medications, less dopamine is released in the motor pathway, and we get fewer movements of tardive dyskinesia.

So, it's really twofold. We have to make sure that we are addressing the dopamine issue that we have, by using VMAT2 inhibitors for anyone, regardless of severity of TD, if they are impacted by the TD. Also, we have to ask the right questions to figure out if the patient is impacted or not.

In my clinical experience, I've found that every person I've diagnosed with TD, eventually I get to some impact where they are able to tell me about things that it does bother them or reduce their functionality or quality of life. But, that could sometimes take months for some people, of being able to connect the dots between A to B.

But, don't give up. It's worth it because when we do find the impact and help our patients to realize it, and we can offer them treatment, their lives can change.

Dr Craig Chepke is a board-certified psychiatrist and a Fellow of the American Psychiatric Association. He attended NYU School of Medicine and completed his residency training at Duke University. Dr. Chepke is the medical director of Excel Psychiatric Associates in Huntersville, NC, as well as a clinical assistant professor of psychiatry at SUNY Upstate Medical University and an adjunct associate professor of psychiatry for Atrium Health. He is a member of the Huntington Study Group and serves on the board of directors for the CURESZ foundation, a nonprofit organization dedicated to improving the lives of people living with schizophrenia.