Treatment with any dopamine antagonist, including antipsychotics, will incur risks for movement disorders, including drug-induced parkinsonism (DIP), akathisia, dystonia, and tardive dyskinesia (TD). While some movement disorders occur during the initial stages of treatment or when treatment is modified, TD occurs after long-term treatment with an antipsychotic and requires different and specific approaches to treatment.
There is a recently approved therapy for schizophrenia that does not inhibit dopamine receptors, and, as a result, does not carry the same risk for TD, but it is not approved for patients with mood disorders, who are the majority of patients taking antipsychotics.
I agree that movement disorders are common in people taking antipsychotics. Looking specifically at TD, it’s thought that about 30% of patients taking typical antipsychotics, about 7% of patients taking atypical antipsychotics without prior exposure to typical antipsychotics, and about 21% of patients taking atypical antipsychotics where their prior exposure is unspecified will develop TD. DIP is also common in people who are taking not just antipsychotics but other dopamine receptor blocking agents.
As a psychiatrist, I am concerned about TD because it can undermine the long-term psychiatric stability of my patients. Although no clinical studies have been conducted to evaluate the impact of treating TD on patients, I have seen the impact of treatment on patients in my clinic. In some cases, patients have reported that they stopped taking antipsychotic medication regularly when they developed TD. Not only does TD impact the patient physically, affecting their daily function, but it can also have profound impacts on their psychosocial functioning.
I’d like to add that although some people may think of movement disorders as only impacting the patient, they can have a significant impact on caregivers—they tend to have higher scores on caregiver burden scales, and have reported that TD has an impact on their daily activities, psychological well-being, and social or professional life.
Partly, it's just historical precedent. The terms have been around for decades, and even though there are many people in psychiatry and neurology who are united in saying that this is an outdated term that doesn't accurately describe the different drug-induced movement disorders, the US Food and Drug Administration (FDA) is still wedded to it. When drugs are approved, they still use this terminology in their package insert. It's unfortunate that the FDA still perpetuates what we think is outdated terminology, but I think as long as they continue to use it, we're going to have an uphill battle to try to get people to stop using it.
I think it's also important to point out that it's not just the FDA. It's still being used in training programs, and I see psychiatric residents still talking about EPS. As you pointed out—EPS is an outdated term for a host of different movement disorders typically associated with drug exposure.
Instead of using the term EPS, we should be differentiating these disorders—this person has acute dystonia, this person has DIP, this person has TD—because the treatments are different, and the term EPS may be contributing to the overuse of anticholinergic therapies in patients where that treatment is not appropriate.
In the old days, everyone reached for anticholinergic therapies for EPS, thinking that they're treating either acute dystonia or DIP. This could lead to mistreatment of many other conditions. Anticholinergics, for example, aren't an appropriate treatment for TD and can make TD movements worse.
I think the emergence of vesicular monoamine transporter 2 (VMAT2) inhibitors for the treatment of TD has brought to the forefront the fact that these really are different disorders, and there are different treatments that are appropriate for many patients that would have previously fallen into the category of EPS.
I also think it's important to mention that, going forward, psychiatric providers are going to have to think carefully regarding the use of anticholinergics such as benztropine because a therapy for schizophrenia was recently approved that works in a cholinergic pathway and may increase the frequency or severity of anticholinergic adverse reactions when used concomitantly with other drugs that produce these reactions.
There hasn't been a lot of time or formal training devoted to teaching psychiatric providers the difference between these movement disorders. I think this was because, in the past, there were no effective treatments for TD. There was almost a psychic blindness that developed to seeing movements, particularly TD. The patient needed to stay on the psychiatric medication, so if you diagnosed TD, there was very little you could do about it beyond switching the patient to a different antipsychotic.
Now that we have effective therapies, people are realizing that it's really important to see this movement disorder, understand it, and treat it.
It's especially important for psychiatric providers to realize that, for the vast majority of these abnormal movements, they will be able to make the diagnosis, and they don't need fellowship training or specialty training to do it. Yes, there may be the rare cases where people have a very unusual movement or where patients may have both TD and DIP, but in general, tardive movements can be easily diagnosed.
TD is a hyperkinetic movement disorder, so we would expect to see excessive, fidgety movements. Although movements can occur anywhere in the body, the vast majority are going to be oro-buccal-lingual symptoms. These include things like excessive blinking, grimacing, lip puckering, lip smacking, and eyebrow furrowing. In the body, you're going to typically see movements in the hands—the so-called piano-playing fingers—or the feet. Sometimes people will move the trunk as well.
DIP, on the other hand, is a hypokinetic movement, so we would expect movements to be slow. Instead of having a lot of facial movement, they may have a paucity of facial movement. It may also be associated with tremor, which is a rhythmic, shaky, fidgety movement.
On a very gross level, which I think is very translatable to general practice, TD movements are fast and fidgety, generally involving the face, and Parkinsonian movements are rhythmic and slow. If you look for these features and keep those two big things in mind, it will help you to identify the vast majority of movements correctly.
In addition to the features Dr Kremens mentioned, the time course usually helps distinguish DIP from TD as well: DIP typically emerges quickly after a patient is either started on a new drug or a dose is increased, while TD begins later in the course of exposure—typically after at least 3 months, except in older individuals where it may occur after only one month of drug exposure.
And I would emphasize that psychiatric providers are fully capable of differentiating a rhythmic, regular movement from the jerky, irregular movements of TD. They have been treating DIP for decades, in many cases without referring their patients to a neurologist. There may be instances where you need to refer a patient to a movement disorder specialist, but the vast majority of cases can be handled by a psychiatric provider.
I start with a global impression of the person and their movement: is it rhythmic, regular, slow, fast, jerky, or irregular? Where is it presenting?
Then I look at the time course of onset: Is this something which presented relatively soon after a dose increase, within the expected time frame of the kinetics of the preparation? Or is this something which appeared out of the blue or insidiously, without respect to ongoing treatment changes?
And then lastly, I check if there have been other changes in treatment and how they may have impacted the movements. For example, consider a patient with mild dyskinesia who discontinued their antipsychotic. Did the movements worsen, as can happen with TD? Or did they improve, which you would expect with DIP? Similarly, a patient’s response to an adjunctive anticholinergic may also indicate which movement disorder they have, as this treatment can make TD movements worse but will improve DIP.
I’d like to add that a very good examination for movement disorders can be done via telepsychiatry, and with additional camera positioning, examination of all 7 items on the Abnormal Involuntary Movement Scale, or AIMS, test should be possible.
The one item that may be difficult to test is rigidity. If you have a patient with paucity of movements and you’re trying to identify if this person is slow for other reasons—maybe they’re on sedating medications, for example—but they don’t have a tremor, it may be necessary to follow up in person.
When I was just starting out, there was no FDA-approved treatment for TD. We would tell patients to stop or reduce the medication. I came to learn from my psychiatric colleagues that this was extraordinarily frustrating because most of the time, they had worked months to years to get this patient stable, and now all of a sudden I was telling them that they were going to have to stop or change this medicine.
Thankfully, with VMAT2 inhibitors we now have 2 FDA-approved, first-line treatments for TD that don’t impact the psychiatric treatment of these patients.
Multiple guidelines—including the American Psychiatric Association (APA), the American Academy of Neurology, and a consensus panel of experts—have recommended VMAT2 inhibitors as first-line therapy for TD.
If you have a schizophrenia spectrum disorder, the idea of stopping the medication does not seem feasible, and even many people with mood disorders may need this medicine for psychiatric stability.
Now that we have FDA-approved treatments for TD, the reflex to stop the antipsychotic is not appropriate in many circumstances.
VMAT2 inhibitors were studied in people with severe mental illnesses. Depending on the study, 60% or more of the individuals had schizophrenia spectrum disorders, and the vast majority of the other subjects in these studies had a mood disorder, especially bipolar disorder. In the studies for each drug, the medication was added to existing medications, so there’s no reason to change underlying therapy when you add either of the approved VMAT2 inhibitors.
I think it was a lack of understanding of the balance between dopamine and acetylcholine in the various pathways within the striatum. Because of that misunderstanding, there was a thought that if it's a movement disorder caused by D2 blockade, it should respond to an anticholinergic.
Now we understand the vast differences between the pathophysiology of TD and DIP and the alteration in the cholinergic-dopaminergic balance. Out of sympathy, I would also say there was probably an aspect of desperation. You had very little to offer people for TD prior to 2017 in the US. There was a hope that maybe this would make the situation better.
I agree. Many of them were trained that benztropine is the appropriate treatment for EPS, and TD fell under the EPS term. We now know that these are separate movement disorders, and that the use of anticholinergics in a patient with TD can make the condition worse.
The APA Guidelines for Schizophrenia indicate that moderate to severe TD should be treated, and that even mild TD should be treated if it is impacting the patient.So, it's incumbent upon us to look for movements, and if we see them, determine the impact that it's having on our patients. It's not for us to make the decision for them. Ask the patient, their family, and their caregivers about the impact of TD movements, and then make an appropriate decision about treatment with VMAT2 inhibitors.
I'll end by saying that there's no minimum score to diagnose TD. If there's an abnormal movement which looks like TD and it is having an impact on the patient, then that patient should be offered appropriate treatment. Often, patients who were not offered treatment and its potential benefits may have minimized the impact of their TD.
It is important for psychiatric providers to ask about the impact of TD across all domains of a patient's life—physical, psychological, social, vocational, educational, and recreational. Examples of questions to ask might be: Do other people notice? Do people at the group home make fun of you? Is your family not able to take you out to a meal or to church or a family gathering because of your movement disorders? Asking the right questions and probing your patients on different aspects of their life can help uncover the impact of TD even in patients who are not fully aware of their movements or who have a lack of insight into their condition.
And reinforce that treatment for TD can be added on to their current medication regimen without making any changes. Don't accept the first no as the end of the conversation; make it an ongoing discussion. Over time, people may decide that they want to consider treatment for TD.
I think it's important that we act as advocates for our patients.
