Put simply, TD is a hyperkinetic movement disorder—too much movement; DIP is a hypokinetic movement disorder—too little movement. However, it is also critical to understand the phenomenology associated with different movement disorders. Let’s consider TD and DIP, the most common DIMDs, as an example.
TD can be associated with chorea, athetosis and, in some cases, dystonia. So, let’s define those phenomenologies. Chorea is randomly flowing movements from one body part to another. Athetosis is slow, writhing movements also flowing from one body part to another. Dystonia is defined as sustained involuntary muscle contractions. TD most often affects the orofacial region, but in greater than half of all patients affects all extremities and even the trunk as well. Common symptoms include lip puckering, facial grimacing, tongue protrusions, excessive blinking, and “piano playing” in the fingers or toes. TD movements are irregular, nonpredictable, and constantly flowing.
DIP, on the other hand, is characterized by an overall paucity of movement and associated with bradykinesia and rigidity. Bradykinesia is a primary symptom of DIP and is defined as small, slow movements. The patient will feel as if they are trying to make big movements but are unable to do so, resulting in difficulty with common activities such as standing from a chair with no armrests. Rigidity is muscle stiffness resulting in resistance to movement. Additionally, 75% of patients with DIP will have tremor at rest, although 25% of patients with DIP will have no tremor. Tremor typically occurs in the jaw, hands, and feet. These 3 phenomenologies are indicative of DIP; however, more advanced DIP may have postural instability and falls. Common additional symptoms include “masked face” with reduced blinking, shuffling gait, and lack of arm swing.
By defining these phenomenologies, we can determine whether our patient’s symptoms are due to TD, DIP, or both.
TD and DIP can also be differentiated based on the onset of symptoms. DIP has acute onset, often starting days to weeks after initiating treatment with or increasing the dose of an antipsychotic. TD, on the other hand, is a late-onset movement disorder, occurring after long-term exposure to an antipsychotic. That’s why we refer to it as “tardive.”
Learning to make the distinction between TD and DIP is essential because they require different treatments. DIP can be treated with anticholinergics, but these medications don’t help with the flowing movements associated with TD and can actually make movement worse, especially in older patients. A correct diagnosis determines the appropriate course of treatment.
I agree. These movements have different underlying causes. Acute DIP results from hypodopaminergic state in the brain while TD results from hyperdopaminergic state. Anticholinergics increase dopamine activity and thus help reduce the severity of DIP, but will worsen TD movements. The American Psychiatric Association (APA) recommends vesicular monoamine transporter 2 (VMAT2) inhibitors, which are the only US Food and Drug Administration (FDA)-approved treatment for TD that has an impact on the patient.
The challenge we encounter in psychiatry is the continued use of terms like extrapyramidal symptoms (EPS) to describe any DIMD experienced by a patient taking antipsychotics. This umbrella term doesn’t adequately differentiate between the movement disorders, like TD and DIP, that require different treatments.
In the 1950s, antipsychotic medications were discovered as a treatment option for various psychiatric conditions. However, some patients receiving these medications developed abnormal movements that were reminiscent of parkinsonism. At the time, anticholinergic medications were commonly used to treat parkinsonism, and clinicians began using them to alleviate the drug-induced movements experienced by patients on antipsychotics. It became common practice to prescribe anticholinergics alongside antipsychotics to address these side effects.
When TD was recognized as a distinct movement disorder associated with long-term antipsychotic use, it was initially grouped together with DIP under the broader classification of EPS. As a result, both conditions were treated with anticholinergics despite the differences in their underlying mechanisms.
For many years, no effective treatment existed for TD, leading to the continued use of the term EPS and the reliance on anticholinergics. This practice has become entrenched in clinical settings despite the approval of VMAT2 inhibitors for the treatment of TD in 2017, and it remains a significant barrier to overcome.
This can be a challenging conversation to have with patients, but it is extremely important. I’ve encountered patients who do not want to discontinue their anticholinergic medication, especially if they have been taking it for a long period of time. This scenario is where I think that patient education is absolutely critical. I want the patient to understand why we are discontinuing the anticholinergic—namely, that it may be making their symptoms worse. I want to engage in a conversation to develop a treatment plan that addresses all of their concerns, including their TD. For my patients with TD, I will explain that anticholinergics are not an appropriate treatment, but VMAT2 inhibitors have been approved by the FDA for the treatment of TD.
The APA guidelines, which contribute to the standard of care, state that patients taking antipsychotics should be assessed for movements during a clinical evaluation at every visit. Further, a structured assessment should be conducted annually or every 6 months in high-risk patients, such as elderly patients, postmenopausal females, patients with a mood disorder, and those with a previous movement disorder.
The Abnormal Involuntary Movement Scale (AIMS) is the standard scale for systematically assessing and quantifying the severity of TD movements. It assesses 7 items—4 regions of the face, where TD most often occurs, upper extremities, lower extremities, and trunk.
By adhering to clinical practice guidelines and the standard of care, we can ensure that TD is identified and treated appropriately. It is worth noting that patients may score a 0 on the AIMS for years while taking an antipsychotic before developing movements. We want to identify and document when a patient’s score jumps plus 1 or plus 2. If movements are detected, we should then ask about impact.
At every clinical encounter, I ask my patients taking antipsychotics if they have noticed movements that they don’t like in their face or body. If they mention or have movements, I ask about impact. Does it bother or embarrass them? And then, importantly, I will ask about treatment. Are they willing to take medication to address it? The APA guidelines recommend treatment for TD that has an impact on the patient, regardless of the severity of movements.
TD can have a profound impact on patients physically, socially, and psychologically. Patients may not be able to properly use their hands, chew their food, or button their shirts. They may isolate themselves from others, and TD can also make it more difficult to manage the patient’s underlying mental health condition. The biopsychosocial impact of TD can be distressing for patients.
I’d add that nobody wants to be the person that the other people on the bus don’t want to sit next to. It’s an instinct probably ingrained into us since childhood. TD can make you feel socially ostracized. And for many patients, these movements have an added impact to an already distressing mental health condition. So, the impetus to treat is impact. Does this bother you enough to start taking a pill every day to make it better?
In my clinical experience, I have found that it is important to initiate treatment for TD, regardless of severity of movements, as soon as possible once a diagnosis has been made if it has an impact on the patient. In fact, the FDA trials for both VMAT2 inhibitors in the market included patients with mild, moderate, or severe TD.
Even mild movements can have a substantial impact, depending on the individual patient’s circumstances. My brief advice to my colleagues would be to be vigilant for DIMDs in patients taking antipsychotics, diagnose TD early and understand the impact of movements on your patient’s life, and consider clinical practice guidelines, which recommend treatment with a VMAT2 inhibitor for TD that impacts the patient.
First, AUSTEDO has a demonstrated efficacy and safety profile, which was established in 2 randomized, placebo-controlled clinical trials. The most common adverse reactions reported in patients with TD treated with AUSTEDO (>3% and greater than placebo) were nasopharyngitis and insomnia. Second, increasing improvement in AIMS total score was observed through 3 years in an open-label extension (OLE) study, with 71% of patients at Week 145 seeing improvement relative to Week 15.
A very important factor for my patients is a reduction in movements and the resulting improvement in their social and emotional well-being. Teva conducted a survey to assess satisfaction among patients taking AUSTEDO XR. Patients reported greater self-esteem and feeling more comfortable with social activities, including spending time with family or working. When discussing treatments, my goal is to help patients understand how reduction of their movements could subsequently help to reduce the impact of TD on their lives.
When starting AUSTEDO XR, all patients with TD begin with a 12-mg dose, which may be increased at weekly intervals by 6 mg/day until the desired symptom control is tolerably achieved. It is important that we find that reasonable dose to achieve therapeutic effect. That is why we increase the dose until we are able to see symptom control. AUSTEDO XR is available in doses from 12 mg to 48 mg, which allows providers to individualize the treatment to the patient’s needs.
I would like to reiterate that using outdated terms like EPS that do not differentiate between movement disorders doesn't just delay diagnosis, but it can really impact the patient. We know that TD can lead to biopsychosocial repercussions for our patients, so it’s really important to understand that TD is distinct from other DIMDs and to identify TD early and treat it with a VMAT2 inhibitor.
I agree. There used to be nothing we, as providers, could do to effectively treat TD. Now, we are equipped with VMAT2 inhibitors, such as once-daily AUSTEDO XR, that can help control the symptoms of TD, and I find that really inspiring. What we need to remain focused on is accurately identifying TD from other DIMDs, like DIP, to ensure that appropriate treatment can be prescribed, and the patient can see the benefit.
