Use AIMS to monitor for and assess tardive dyskinesia (TD) symptoms¹

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Recognizing Tardive Dyskinesia (TD) and Understanding Its Impact

A Video-Based Review of Movement Disorders

Doctor Karunapuzha:

Welcome to this program, Recognizing Tardive Dyskinesia and Understanding Its Impact.

My name is Cherian Karunapuzha, Medical Director and consulting neurologist at Meinders Center for Movement Disorders in Oklahoma City, Oklahoma.

This program will provide an overview of tardive dyskinesia, or TD, and as part of this comprehensive discussion, I’ll be guiding you through a video-based review of movements that you may often encounter in your clinics. Then, we will discuss practical considerations for distinguishing TD from other movement disorders and hear from patients about the impact of TD on their lives.

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This promotional program was developed by Teva in conjunction with therapeutic experts, and I am presenting on behalf of Teva.

I have received compensation from Teva to give this presentation.

Doctor Karunapuzha:

This promotional program was developed by Teva in conjunction with therapeutic experts, and I am presenting on behalf of Teva. I have received compensation from Teva to give this presentation.

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Consequences of Treatment with Dopamine Receptor Blocking Agents (DRBAs) (eg, typical and atypical antipsychotics, prokinetics, antiemetics)

Acute Dystonia

Drug-Induced Parkinsonism

Acute Akathisia

Tardive Dyskinesia

Doctor Karunapuzha:

Drug-induced movement disorders are a known consequence of dopamine receptor blocking agents. In your clinic, you may encounter patients at risk of developing drug-induced movement disorders due to typical or atypical antipsychotics they are taking for mental health conditions or prokinetics and antiemetics for gastrointestinal issues.

The most common drug-induced movement disorders associated with dopamine receptor blocking agents are acute dystonia, drug-induced parkinsonism, or DIP, acute akathisia, and TD. The term extrapyramidal symptoms, or EPS, is still broadly used in psychiatry and by the FDA to describe motor symptoms linked with the use of dopamine receptor blocking agents, but this concept fails to adequately differentiate between specific disorders. For this reason, many healthcare professionals are moving away from this term in favor of more precise descriptions of a patient’s symptoms.

Each of these movement disorders is associated with distinct phenomenologies, which we will discuss in this program, as well as different treatment options.

In order to appropriately treat movement disorders, it is important to differentiate and make an accurate diagnosis, because treatment for one may worsen symptoms of another. Understanding the underlying phenomenologies can help you to identify movement disorders like TD in your clinic.

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TD is a chronic, irreversible hyperkinetic movement disorder

Doctor Karunapuzha:

TD is a persistent and often irreversible hyperkinetic movement disorder caused by chronic exposure to dopamine receptor blocking agents.

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Frequently undiagnosed or misdiagnosed

Any presentation of TD may impact patients’ lives

FDA-approved treatments are available

Footnote:

FDA, US Food and Drug Administration.

Doctor Karunapuzha:

TD is often underdiagnosed and undertreated, but understanding the characteristic movements associated with it can empower clinicians to better identify it.

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Orofacial TD: Lip pursing and facial grimacing

Doctor Karunapuzha:

This video demonstrates some common TD symptoms, including orofacial movements, such as lip pursing or grimacing, TD affecting the trunk, and movements in the hands and feet.

As you watch the videos in this presentation, one of the key elements that I want you to focus on is trying to evaluate patients systematically, from top to bottom. As you do this, try to keep a zoomed-out lens as you assess these patients.

The eye will be naturally drawn to larger or more obvious movements. This can make it easier to miss some of the more subtle movements happening in other body parts.

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Frequently undiagnosed or misdiagnosed

Any presentation of TD may impact patients’ lives

FDA-approved treatments are available

Footnote:

FDA, US Food and Drug Administration.

Doctor Karunapuzha:

It is critical to recognize TD, because it can significantly impact various aspects of patients' lives and complicate the management of their underlying mental health disorder. Fortunately, FDA-approved treatments for TD are available.

Today, we will address how TD can be identified, accurately diagnosed, and appropriately treated.

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Movements

Hyperkinetic:

Non-rhythmic: Myoclonus, Dystonia, Chorea, Athetosis, Ballism, Stereotypy, Tic

Rhythmic: Tremor

Hypokinetic:

Parkinsonism: Drug-induced, Parkinson’s disease (or other neurodegenerative disorders)

Doctor Karunapuzha:

The phenomenology of TD can overlap with that of other movement disorders. As a result, clinicians must be able to identify the different movements that may present in clinics. A useful way to classify movement disorders is as hyperkinetic, characterized by excessive movement, or hypokinetic, characterized by too little movement.

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Movements

Hypokinetic:

Parkinsonism: Drug-induced, Parkinson’s disease (or other neurodegenerative disorders)

Doctor Karunapuzha:

We’ll start by looking at hypokinetic movement disorders, or hypokinesias, which are identified by a paucity of voluntary and automatic movements that are not related to weakness or spasticity. These disorders are marked by a reduction in movement or movements that are slower and of lesser amplitude. The most common cause of hypokinesia is parkinsonism, which can arise from medication exposure, leading to DIP, or from neurodegenerative conditions such as Parkinson’s disease, progressive supranuclear palsy, or multiple system atrophy.

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Parkinsonism is the most common cause of hypokinetic movements

• Characterized by akinesia/bradykinesia
• Often associated with rigidity
• Clinical signs include fatigue and decrement of repetitive alternating movements (eg, finger or foot tapping)

Parkinsonism, while primarily hypokinetic, may be associated with resting tremor

Doctor Karunapuzha:

Parkinsonism is distinguished by bradykinesia, or slowness of movement, and rigidity. Clinically, bradykinesia associated with parkinsonism is detectable by observing fatigue and a decrement in repetitive alternating movements, such as finger or foot tapping. Although parkinsonism is primarily a hypokinetic movement disorder, it may be associated with resting tremor.

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Shuffling gait and decreased arm swing

Doctor Karunapuzha:

The patient in this video illustrates some key parkinsonian features. She has a characteristic shuffling gait with decreased arm swing, which can indicate bradykinesia and the stiff, stooped posture you can see when she moves can indicate rigidity. When patients with Parkinson's have both bradykinesia and rigidity, you can see both of them intruding in different body parts. For example, if the patient is slow in the way they walk and they have stiffness or rigidity in the body, you will see a classic stooped posture with a very short, shuffling gait.

The patient in this video also exhibits fatigue and decrement in repetitive movements. The motion starts off big, and over time the movements are reduced in amplitude.

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Masked face

Doctor Karunapuzha:

In this video, you can see examples of masked face, a key symptom of parkinsonism, reflecting an overall paucity of voluntary and automatic movements, such as blinking. You can see that the patient barely blinks. They have a stiff, rigid appearance with a lack of expression.

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It is important to differentiate parkinsonism from TD, as treatments for one may worsen the other

Doctor Karunapuzha:

Differentiating parkinsonism from TD is crucial, as certain medications used to treat parkinsonism, such as anticholinergics, may exacerbate symptoms of hyperkinetic disorders, such as TD.

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Movements

Hyperkinetic:

Rhythmic: Tremor

Doctor Karunapuzha:

Now we’ll look at hyperkinetic movement disorders, sometimes called dyskinesias, which are characterized by excessive movement with increased speed and/or amplitude.

TD frequently manifests as a combination of hyperkinetic movements, which we can begin to differentiate by first determining whether they are rhythmic, as in tremor, or irregular.

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Regularity and Rhythmicity Distinguish Tremor From TD

Tremor is

• Involuntary, usually regular, and rhythmic oscillation of a body part around a fixed point
• The most common movement disorder encountered in clinical practice

In parkinsonism, tremor (hyperkinesia) may coexist with bradykinesia and rigidity (hypokinesia)

Doctor Karunapuzha:

Tremor is defined as the oscillation of a body part around a fixed point. It is the most commonly encountered movement disorder in clinical practice. It typically has a consistent frequency, though the amplitude can vary. This regularity and rhythmicity distinguishes tremor from the random movements associated with TD.

Tremor can be categorized based on its occurrence in relation to position or movement, such as rest, posture, action, or task-specific. Further characterization of tremor involves assessing its frequency and amplitude as well as identifying the specific body part involved, such as the head, upper body, or lower extremity. It is important to note that tremor can coexist with other phenomenologies.

For example, resting tremor combined with bradykinesia and rigidity is a hallmark of parkinsonism.

Tremor associated with dystonia may be less rhythmic, featuring both slow and fast phases. In these cases, the tremor is considered part of the dystonia.

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Essential tremor

Parkinsonian tremor

Dystonic tremor

Doctor Karunapuzha:

This video features a side-by-side comparison of patients with essential tremor, parkinsonian tremor, and dystonic tremor. As you watch this video, remember that tremor is a rhythmic oscillation, meaning it has a set frequency. When you see patients with a tremor, you can create a beat in your mind as you look at the movement, and that will help you determine whether there is a rhythm to the movement.

For example, [Dr. Karunapuzha vocalizes rhythm as he demonstrates]. You use that as a reference when you look for tremors.

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Essential Tremor

Parkinsonian Tremor

Dystonic Tremor

Doctor Karunapuzha:

In the frame on the left, the first patient shows how his essential tremor activates when he tries to sustain a posture. The second patient demonstrates how essential tremor activates when she tries to do an action. If you look at these tremors, they have a set frequency.

In the middle frame, you can see that parkinsonian tremors tend to have a slower frequency. Resting tremor appears while the body part is at rest.

In the frame on the right, you will see 2 patients with cervical dystonia. These patients showcase how the tremor changes in certain vectors or angles. For example, the tremor becomes more pronounced when her head is in a more central location, and as she turns her head, the tremor becomes less intense. This variability in intensity tells us that the tremor has no set rhythm but is based on how the dystonic muscles pull the head away from neutral alignment. That creates a tremor-like appearance.

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Movements

Hyperkinetic:

Non-rhythmic: Myoclonus, Dystonia, Chorea, Athetosis, Ballism, Stereotypy, Tic

Doctor Karunapuzha:

Next, we’ll discuss nonrhythmic or irregular, hyperkinetic movements. Some of these phenomenologies are associated with TD. Let’s review what you can look for in your clinic to help you differentiate these movements and, subsequently, accurately identify TD.

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Involuntary Movements

Amplitude / Speed

Dystonia, Athetosis, Chorea, Ballism, Myoclonus

Doctor Karunapuzha:

Irregular hyperkinetic movements are categorized based on attributes including speed, amplitude, duration, pattern—such as repetitive or continuous—and suppressibility.

For instance, myoclonus, dystonia, chorea, athetosis, and ballism can be differentiated primarily based on the speed and amplitude of the movements. These movements are involuntary and are typically not suppressible.

Tics, stereotypy, and akathisia are distinct from other involuntary movements because they may be suppressible. Tics are often associated with an urge to perform the movement followed by a sense of relief. In contrast, stereotypy may be induced by an internal sensory stimulus or an unwanted feeling. Akathisia is characterized by restlessness and an urge to move.

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Movement: Keywords

Tremor: Rhythmicity

Myoclonus: Shock-like jerks

Stereotypy: Nonpurposeful, coordinated, repetitive, patterned movements without urge

Tics: Stereotyped, suppressible, intermittent movements with urge

Chorea: Randomly flowing jerky movements

Athetosis: Slow, writhing movements

Ballism: Violent flinging

Dystonia: Abnormal posture

Akathisia: Feeling of restlessness

Doctor Karunapuzha:

Recognizing and differentiating hyperkinetic movements can be aided by identifying keywords that describe their distinctive phenomenological characteristics. These keywords serve as a shorthand for clinicians to quickly identify specific movement disorders.

For instance, "tremor" may be associated with rhythmicity. Myoclonus is characterized by sudden, shock-like jerks due to either active muscle contraction or sudden relaxation. Stereotypy refers to seemingly nonpurposeful, coordinated, repetitive, and patterned movements that occur without an urge.

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Tics in neck

Doctor Karunapuzha:

“Tics” are stereotyped and suppressible, with intermittent movements often distinguished from other disorders, such as TD, by the presence of an accompanying urge. In this video, you can see an example of a patient with tics in the neck.

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Mild lower facial chorea

Doctor Karunapuzha:

Chorea is defined by abrupt, unsustained, and irregular movements that transition randomly between different body parts. In this video, you can see the purposeless, jerky movements across her face or legs. These movements are unpredictable; there’s no rhyme or reason to which body part acts next.

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Movement: Keywords

Tremor: Rhythmicity

Myoclonus: Shock-like jerks

Stereotypy: Nonpurposeful, coordinated, repetitive, patterned movements without urge

Tics: Stereotyped, suppressible, intermittent movements with urge

Chorea: Randomly flowing jerky movements

Athetosis: Slow, writhing movements

Ballism: Violent flinging

Dystonia: Abnormal posture

Akathisia: Feeling of restlessness

Doctor Karunapuzha:

Athetosis is a slower variation of chorea comprising writhing movements that resemble dystonia. However, unlike dystonia, these movements are not sustained, patterned, repetitive, or associated with pain.

Ballism is recognized as a more forceful, high-amplitude version of chorea characterized by flinging movements.

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Jaw dystonia

Doctor Karunapuzha:

Dystonia involves sustained muscle contractions that often result in twisting and repetitive movements or abnormal postures, with contractions that can vary widely from short to sustained durations.

You can see an example of these abnormal postures in this video, which includes patients with jaw or cervical dystonia. You can see as the patient tries to open his mouth, his jaw starts to involuntarily close. The next patient tries to keep a straight posture, but her head or chin is being tucked down forcibly. With dystonia, you can see the sustained muscle contraction or the tension keeping the body in an abnormal posture.

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Movement: Keywords

Tremor: Rhythmicity

Myoclonus: Shock-like jerks

Stereotypy: Nonpurposeful, coordinated, repetitive, patterned movements without urge

Tics: Stereotyped, suppressible, intermittent movements with urge

Chorea: Randomly flowing jerky movements

Athetosis: Slow, writhing movements

Ballism: Violent flinging

Dystonia: Abnormal posture

Akathisia: Feeling of restlessness

More than 1 hyperkinetic movement may be present in the same patient

Doctor Karunapuzha:

Lastly, "akathisia" is an innate sense of restlessness, which is extremely disconcerting to the patient and does not improve with movement or sustaining a particular body posture.

When characterizing movements, it’s important to not only keep these keywords in mind but also consider that more than 1 hyperkinetic movement may be present in the same patient.

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Persistent abnormal movements in at least 1 body area

• Facial movements are most common, but TD may affect other parts of the body
• Movements are non-rhythmic, choreoathetotic
• May be associated with dystonia

Prior or current prolonged exposure of ≥3 months to a DRBA (or exposure of 1 month for patients ≥60 years)

Other possible etiologies excluded

Doctor Karunapuzha:

TD is characterized by movements that are irregular, choreoathetotic, and may be associated with dystonia. TD is diagnosed based on the persistence of these abnormal movements in at least 1 body area. The orofacial region is most common, but TD may affect the entire body.

The diagnosis of TD requires prior or current exposure to dopamine receptor blocking agents. Other possible causes, which may include structural brain damage, metabolic disorder, autoimmune conditions, and neurodegenerative diseases, must be ruled out.

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98% of patients with TD reported experiencing moderate to severe impact in at least 1 area of their lives*

Footnote:

*From an interim analysis of clinician-reported measures in 208 patients from the IMPACT-TD registry. Patients with a total motor AIMS score of 1 to 6 experienced moderate to severe impact.

Doctor Karunapuzha:

TD can significantly impact patients’ lives in many ways.

In an ongoing, real-world study, 98% of patients reported experiencing the impact of TD in at least 1 area of their lives.

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Psychological/Psychiatric*

>75% reported feeling embarrassed in social situations

Social*

~60% said their movements prevented them from leaving the house

Vocational/Educational/Recreational*

>50% reported their movements limited them at work

Physical*

>60% said movements impacted their sleep

Footnote:

No clinical studies have been conducted to evaluate the effects of treating TD on these outcomes.

Doctor Karunapuzha:

TD impacted patients socially and psychologically—approximately 60% indicated that their movements restricted them from leaving the house, and more than 75% of patients reported feeling embarrassed in social situations. It impacted them physically, frequently affecting their sleep, and for more than half of patients, TD limited their abilities at work.

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Social

When it gets really ramped up and the whole deal,

[Video plays]

Doctor Karunapuzha:

You can truly get a sense of the impact of TD when patients share their own experiences.

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Severity of Movements ≠ Severity of Impact

Doctor Karunapuzha:

Regardless of the severity of movements, treatment should be considered if TD has an impact on the patient. It is important for clinicians to understand that their perception of the severity of movements may not equal the patient’s experience of impact.

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[Video plays]

Doctor Karunapuzha:

Let’s look at this video as an example. First, we will play the video without sound.

When we remove the audio, it is easier to assess some of her more subtle movements. As she is speaking, you can see small movements on her eyelids and tightness in her neck.

These movements appear to be very mild and not necessarily bothersome.

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Doctor Karunapuzha:

When we play the same video with sound, you will hear the actual impact of these so-called mild movements on her.

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I’m a psychotherapist and I sit for an hour at a time.

[Video, which includes audio, plays.]

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[None]

Doctor Karunapuzha:

So as you can see, the patient is distraught, almost to the point she wants to retire, while the clinician may barely see these movements.

There are 2 important lessons to be learned from these videos:

First, subtle movements are easy to miss when you are listening to the patient as well, because it’s difficult to focus on both tasks.

And second, there can be a disconnect between the movements the clinician sees and the impact the patient experiences.

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More than half of patients with very mild to mild TD experience moderate to severe impact*

Treatment should be considered for TD that has an impact on the patient

Footnote:

*From an interim analysis of clinician-reported measures in 266 patients from the IMPACT-TD registry. Severity of TD movements was assessed using the CGIS-TD scale.

Doctor Karunapuzha:

And this is not an isolated example. In a real-world study, more than half of patients with very mild to mild TD experienced a moderate to severe impact on their lives, highlighting the considerable burden that even mild symptoms can impose.

Consequently, the impact of TD should help inform the decision to initiate treatment.

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Antipsychotic change/reduction/withdrawal may

• Fail to improve TD
• Induce withdrawal dyskinesia
• Undermine patients’ psychiatric stability

Discuss with the prescribing HCP before modifying the antipsychotic dose

Anticholinergics can worsen TD symptoms and are not recommended in patients with TD

Consider gradually discontinuing in patients with TD

VMAT2 inhibitors are the only FDA-approved treatment for TD

Footnote:

HCP, healthcare professional; VMAT2, vesicular monoamine transporter 2.

Doctor Karunapuzha:

Once a patient is diagnosed with TD, there are several treatment considerations. It is important to discuss with the prescriber before modifying the antipsychotic dose, because changing the antipsychotic or modifying the dose may fail to improve TD, induce withdrawal dyskinesia, or crucially, may undermine the patient’s psychiatric stability.

Another important consideration is whether the patient is currently taking anticholinergics.

Although anticholinergics are indicated for the treatment of DIP, these drugs can exacerbate symptoms of TD and are not recommended in these patients. If you have a patient with TD who is taking an anticholinergic, consider gradually discontinuing the medication.

The only FDA-approved treatment for TD is a VMAT2 inhibitor.

In summary, TD is a consequence of treatment with dopamine receptor blocking agents that can significantly impact patients’ lives. In order to accurately diagnose and appropriately treat TD, it is necessary to recognize and identify TD-associated movements. VMAT2 inhibitors are the only FDA-approved treatment for adults with TD. The differential diagnosis is important to ensure that the patient receives the correct treatment.

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Doctor Karunapuzha:

I hope you found this content meaningful and relevant for your clinical practice. Thank you so much for watching this video.

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Teva