Hero

Videos

Slideshows

Articles

Podcasts

Poll

Tardive dyskinesia is an irreversible movement disorder that causes involuntary movement outside of the patient's control. Three-year open-label data from the Movement Disorder Center shows TD treatment achieved sustained improvement in AIMS score and treatment response rates indicative of clinically meaningful long-term benefits.

Robert Hauser, MD, one of the authors of this study, discussed the results with 

is a professor of neurology, molecular pharmacology, and physiology at the University Of South Florida Morsani College Of Medicine, in Tampa. He serves as Director of the Clinical Signature Interdisciplinary Program in Neuroscience and as Director of the USF Health Byrd Parkinson's Disease and Movement Disorders Center.

Learn about the results of the recent study on deutetrabenazine and the ways it is helping patients with tardive dyskinesia. 

The New Treatment for Tardive Dyskinesia 

There are a few things that we all agree on, as reflected in a recent consensus statement.

How the Experts Manage Tardive Dyskinesia

, observed in May to promote awareness and understanding of mental health conditions, about half of the states recognized the first week of the month as Tardive Dyskinesia Awareness Week because few persons know about the condition and many do not recognize it.

 of patients taking antipsychotics and other medications, 58% were not aware that antipsychotics can cause involuntary movements or tardive dyskinesia.

As new drugs have become available to treat patients with tardive dyskinesia, effective and safe application has been limited by knowledge gaps and misunderstanding.

Numbers don’t tell the whole story, but gaining a better sense of tardive dyskinesia’s frequency, risks, and impact on patients’ quality of life can help improve treatment efforts and enhance outcomes.

The following facts and figures provide a brief overview.

 affects an estimated 500,000 persons in the United States. About 60% to 70% of cases are mild, and about 3% are extremely severe. Particularly at risk are patients who have been treated for schizophrenia, schizoaffective disorder, or bipolar disorder. Persistent and irreversible tardive dyskinesia is most likely to develop in older persons.

Tardive dyskinesia’s relative significance as a clinical problem and the need for treatment have been questioned since the disorder was first recognized, according to Stanley N. Caroff, MD, Perelman School of Medicine, University of Pennsylvania, in a recent 

 Tardive dyskinesia had been thought to be uncommon and restricted to patients with chronic mental illness, but recent evidence has shown that anyone exposed to dopamine-receptor blocking drugs, not just persons with chronic mental illness, may be at risk.

The cumulative incidence is about 4% to 5% annually; the prevalence rate is 20% to 30%.

Younger patients are at risk and may be particularly susceptible to more generalized and dystonic movements, but older age is a major risk factor.

The annual incidence in patients older than 45 years is 15% to 30% after 1 year of treatment; the prevalence rate is about 50% to 60%.

Tardive dyskinesia has been linked with female gender, race, higher ratings of negative symptoms and thought disorder, greater cognitive impairments, acute drug-induced movement disorders, substance abuse, and diabetes.

Older adults and patients with schizophrenia may be at greatest risk, but patients with mood disorders are at risk and have been considered to be at high risk.

Regardless of diagnosis, tardive dyskinesia is not rare and anyone exposed to treatment with antipsychotics is at risk.

First- vs second-generation antipsychotics

A 6- to 12-fold reduction in tardive dyskinesia risk was found with newer second-generation antipsychotics (SGAs) compared with haloperidol.

The relative risk of tardive dyskinesia with SGAs is significantly less on average than that with older first-generation antipsychotics. The risk associated with clozapine is probably least.

The SGAs retain some risk. No currently available antipsychotic is risk-free.

Additional risk factors for the development and persistence of tardive dyskinesia are longer duration of antipsychotic treatment and greater cumulative drug doses.

The conventional wisdom that tardive dyskinesia is unimportant may be the result of patient selection bias or the lack of rigorous investigations, Dr Caroff noted. In the early reports of older patients with chronic illnesses showing indifference, up to two-thirds seemed unaware of tardive dyskinesia movements. However, in a recent survey of outpatients with possible tardive dyskinesia, 70% to 80% were aware of their movements and 50% to 60% felt self-conscious or embarrassed by them.

As clinicians assess the seriousness of tardive dyskinesia and the need for treatment, they should consider the objective severity of the movements and the functional impact on patients, Dr Caroff suggested.

He added that correlations between tardive dyskinesia and impaired cognition, poor response to treatment, risk of relapse, and other factors are confounded by the effect of the underlying psychiatric illness-patients with severe psychoses and poor prognoses receive higher doses of antipsychotics for longer periods with poor adherence, resulting secondarily in a greater incidence of tardive dyskinesia.

RealâWorld Evaluation Screening Study and Registry of Dyskinesia in Patients Taking Antipsychotic Agents (RE-KINECT) 

 showed the following effects of involuntary movements on patient health-related quality of life (HRQoL):

Close to 30% of patients who had possible tardive dyskinesia reported moderate-to-extreme problems in performing their usual activities (eg, work, housework, and leisure activities) compared with just under 20% of patients who did not.

Almost half of patients who had possible tardive dyskinesia experienced moderate-to-extreme anxiety or depression compared with just under 40% of patients who did not.

Just more than 20% of patients who had possible tardive dyskinesia reported moderate-to-extreme mobility problems compared with about 12% of patients who did not.

Utility scores in a regression model showed poorer perceived QoL in patients who had possible tardive dyskinesia and reported “a lot” of severity or “a lot” of impact on daily activities compared with patients who did not.

“The RE-KINECT study provides valuable insights into the real-world and personal impact the involuntary movements from possible tardive dyskinesia may have on the everyday life of a patient,” said Dr Caroff. “The findings from RE-KINECT are valuable for informing treatment decisions in clinical practice and demonstrate the importance of including assessments from patients and caregivers on the severity and social impact of the stigmatizing movements of tardive dyskinesia.”

. Alexandria, VA: Mental Health America. Accessed May 28, 2019.

Neurocrine Biosciences honors Mental Health Month and raises awareness of tardive dyskinesia and its impact on patients

 [press release]. Biospace. Accessed May 28, 2019.

 Alexandria, VA: Mental Health America. Accessed May 28, 2019.

Overcoming barriers to effective management of tardive dyskinesia.

. 2019 Apr 4;15:785-794. doi: 10.2147/NDT.S196541. eCollection 2019.

Neurocrine Biosciences presents new data from RE-KINECT, the largest Real-World Screening Study of Possible Tardive Dyskinesia, demonstrating the effect of involuntary movements on patient quality of life

 [press release]. PRNewswire. Accessed May 28, 2019.

Numbers don’t tell the whole story, but gaining a better sense of the frequency, risks, and impact on patients’ quality of life can help improve treatment efforts and enhance outcomes.

Tardive Dyskinesia Facts and Figures

Atypical antipsychotics cause tardive dyskinesia (TD) at rates that are higher than previously thought. There are ways to prevent, manage, and treat TD, and this podcast will guide you through those steps from FDA-approved medications to off-label therapies.

For more infomation, see the accompanying article to this podcast: 

Dr Aiken is Instructor in Clinical Psychiatry at the Wake Forest University School of Medicine and the Director of the Mood Treatment Center in Winston-Salem, NC. He is Editor in Chief of 

 and Bipolar Disorder Section Co-Editor for Psychiatric Times.

There are ways to prevent, manage, and treat TD, and this podcast will guide you through those steps from FDA-approved medications to off-label therapies.

A Practical Guide to Tardive Dyskinesia

Once thought untreatable, we now have two FDA-approved medications for TD and a handful of off-label options. More in this research update.

7 Ways to Treat Tardive Dyskinesia

Crucial to ameliorating pharmacotherapy-associated tardive dyskinesia (TD) is recognizing the impact of TD on patients’ lives. Results from the RE-KINECT 

, presented at the Congress of the Neuroscience Education Institute, which took place this past fall in Orlando, Florida, demonstrated the prevalence and disruptive impact of involuntary movement in patients with suspected TD.

, presented at the same meeting, offered a consensus approach to clinical guidelines for TD.

The RE-KINECT study is a prospective real-world clinical trial (NCT03062033) exploring issues related to TD in outpatients receiving antipsychotics (N=738).

 The study researchers looked at a subset of 204 patients with clinician-confirmed possible TD.

 These patients had at least 3 months’ lifetime exposure to antipsychotic agents and were at least 1 month into a diagnosed psychiatric disorder. “Possible TD” was based on clinician observation of involuntary movements in four body regions: head, trunk, upper extremities, and lower extremities. Scores on the Sheehan Disability Scale (SDS) and EuroQoL 5-Dimensional questionnaire (EQ-5D-5L) also figured into baseline data.

Of the 204 patients, 111 (54%) had schizophrenia/schizoaffective disorder and 93 (46%) had a mood or other psychiatric disorder. Although the investigators found that patients with mood disorders were more likely to be older, female, and racially white compared with patients with schizophrenia/schizoaffective disorder, TD affected both groups of psychiatric patients equally. More than 30% of patients in each group reported that involuntary movements impacted their activities of daily living, productivity, and ability to socialize.

Another subanalysis of the same study, however, found that greater risk of TD severity 

 This RE-KINECT subanalysis focused on patients who were age 55 and older because, although TD is thought to be associated with longer exposure to antipsychotic drugs, it also manifests in older persons after shorter courses of antipsychotic therapy.

Of the 300 patients in the subgroup analysis, 114 (38%) had clinician-confirmed possible TD and 186 (62%) had no visible involuntary movements or had movements that were inconsistent with TD. The researchers found that the highest frequencies of severe abnormal movements affected the head/face (25%) and upper extremities (14%). The researchers also determined that patients in the possible TD group were less likely to be married, more likely to live in care homes, and more likely to have longer lifetime exposure to antipsychotics than the comparator group. Although further research is needed, the investigated stated that limited support systems and reduced quality of life appear to be associated with greater risk and severity of TD in this older population.

Also, in light of the availability of vesicular monoamine transporter 2 (VMAT2) inhibitors for treatment of TD, calls for updated clinical guidelines led to a the conducting of a preliminary consensus using a modified Delphi process.

 The endeavor included a steering committee of 11 experts in TD and surveyed psychiatrists and neurologists.

Respondents unanimously agreed that treatment with first generation antipsychotics, older age, and longer cumulative exposure to antipsychotics were risk factors for TD. Points of unanimous agreement regarding monitoring for TD were that all patients receiving dopamine receptor blocking agents should be screened for TD and that the Abnormal Involuntary Movement Scale should be used as the standard assessment for monitoring TD severity. As for treatment, participants unanimously agreed that discussion of treatment options with patients/caregivers was an imperative, diagnosis of TD was an indication for modification of the antipsychotic regimen, and patients should be offered treatment with a VMAT2 inhibitor.

1. Cutler AJ, Caroff SN, Tanner CM, et al. 

Presence and impact of possible tardive dyskinesia in patients prescribed antipsychotics: results from the RE-KINECT study

2. Caroff SN, Citrome L, Meyer J, et al. 

A modified Delphi consensus approach to clinical Guidelines for tardive dyskinesia

RE-KINECT, a real-world, prospective tardive dyskinesia screening study: an evaluation of baseline characteristics in older patients

. Am J Geriatr Psychiatry. 2019;27:S176-s178.

Tardive dyskinesia hits affected populations hard, especially older folks with poor support systems.

An Equal-Opportunity Condition

Recent studies and reviews report great progress in bringing TD under control.

Looking Ahead: Tardive Dyskinesia Care

Dr Aiken is Instructor in Clinical Psychiatry at the Wake Forest University School of Medicine and the Director of the 

in Winston-Salem, NC. He is Editor in Chief of 

There are two types of tardive dyskinesia (TD), and understanding the difference is essential in this era where this once hopeless syndrome is now treatable. The reason is that one of them may not respond to medications in the way we expect. This “type” is actually not TD at all-it is spontaneous dyskinesia (SD).

SDs were first described in patients with schizophrenia by Emil Kraeplin and Eugen Bleuler in the early 1900s. They are part of the disease process of schizophrenia and occur in patients who have never taken antipsychotics, as well as those who have. They look identical to TD, but are not caused by antipsychotics, whereas TD by definition is a consequence of antipsychotic exposure.

 In fact, SDs tend to improve with antipsychotics because they are part of the disease process itself.

How do we know they are part of the disease process? SDs wax and wane, as does TD, but the spontaneous ones rise with the intensity of the psychotic symptoms and fall when they improve. When psychosis is worse, they get worse. These dyskinesias are part of the genetic vulnerability to schizophrenia. Though rare in the general population, SDs are seen in schizotypal personality disorder and are two to three times more common in the first-degree relatives of patients with schizophrenia.

SDs are fairly common in schizophrenia and worsen with the duration of illness. Prevalence rates in patients with schizophrenia are low (4%) at the start of the illness but rise to 40% in antipsychotic-naÃ¯ve patients over age 60.

 They are rare in the general population, occurring at a rate of 29 per 100,000 life years, but more common in the elderly and those with brain injuries.

 TD is also more prevalent in those groups, leading some to speculate that TD and SDs share a common etiology.

 However, this doesn’t explain the elevated risk of TD in affective disorders, where SDs are virtually absent.

The new VMAT2 inhibitors for TD-valbenazine and deutetrabenazine-were developed to address part of the known pathophysiology of TD: dopaminergic hypersensitivity. They are effective for TD, with a number needed to treat (NNT) between 4 and 7.

 But will they work for SDs? After all, these dyskinesias have a different etiology and may arise from different biological pathways. SDs improve, rather than worsen, with antipsychotics. How they will respond to VMAT2 inhibitors is an open question, but a neglected theory of schizophrenia may point the way toward an answer.

That theory is dopamine hypersensitivity. There is evidence from biological and family studies that hypersensitivity of the dopamine system is a risk factor for schizophrenia, and that it plays a causative role in SD just as it does in TD.

 If that is true, the SDs would improve with VMAT2 inhibitors, and psychosis may improve with these agents as well.

 Indeed, one of the first medications for psychosis, and one that actually preceded the antipsychotics, was reserpine; a VMAT2 inhibitor.

TD is ripe with paradox. SDs actually improve with antipsychotics, while TDs may 

to improve, because antipsychotics can mask tardive movements through their Parkinsonian effects.

 As part of the disease process, SDs may worsen when antipsychotics are discontinued. TD can worsen during antipsychotic withdrawal as well, in the form of 

 With all of this uncertainty, measurement is essential.

Before starting a VMAT2 inhibitor, rate the symptoms with an 

. Patient report is not enough, as awareness of the problem tends to be low. If there’s no improvement after two months, taper off the VMAT2 inhibitor and measure once more a few months later to see if the movements are worse without treatment.

1. Tenback DE, van Harten PN. Epidemiology and risk factors for (tardive) dyskinesia. 

2. Peralta V, Campos MS, De JalÃ³n EG, et al. Motor behavior abnormalities in drug-naÃ¯ve patients with schizophrenia spectrum disorders. 

3. Mittal VA, Neumann C, Saczawa M, et al. Longitudinal progression of movement abnormalities in relation to psychotic symptoms in adolescents at high risk of schizophrenia. 

4. Merrill RM, Lyon JL, Matiaco PM. Tardive and spontaneous dyskinesia incidence in the general population. 

5. Solmi M, Pigato G, Kane JM, et al. Treatment of TD with VMAT-2 inhibitors: a systematic review and meta-analysis of randomized controlled trials. 

6. Skaff R. Valbenazine and Deutetrabenazine as possible treatments for neuroleptic-induced supersensitivity psychosis and antipsychotic dependence. 

Managing the Side Effects of Psychotropic Medications,

 2nd edition,. Washington, DC: American Psychiatric Press; 2018.

8. D'Abreu A, Akbar U, Friedman JH. TD: Epidemiology. 

Some dyskinesias improve with antipsychotic treatment, and these types are more common than thought. More in this podcast.

Not All That Writhes Is Tardive Dyskinesia

 associated with tardive dyskinesia (TD) among patients with psychiatric disorders taking antipsychotic medications.

Antipsychotic medications have been extensively used to treat people with chronic mental illnesses, such as schizophrenia. These drugs, however, have also been associated with a wide range of adverse effects, including movement disorders, such as TD, a problem often seen as repetitive involuntary movements around the mouth and face.

TD is often irreversible and can be debilitating. “The symptoms can increase the social stigma of patients with comorbid psychiatric disorders, negatively impact quality of life, and potentially increase medical morbidity and mortality,” stated researchers, led by Oscar Patteron-Lomba, Manager, Analysis Group in Boston, MA. “An increased risk of developing tardive dyskinesia has been associated with factors such as older age, female sex, underlying mental illness, and long-term use and higher doses of antipsychotics.”

The association of TD with the use of typical versus atypical antipsychotics has been evaluated, with mixed results. No predictive models to assess the joint effect of clinical characteristics on TD risk have been developed or validated in the US.

Using a retrospective database analysis, Patterson-Lomba and colleagues

 identified a total of 189,415 patients; 66,723 with bipolar disorder; 68,573 with depressive disorder; and 54,119 with schizophrenia. These adult patients, who had 6 months of data prior to the index date, were identified from Medicaid claims from six US states. The index date was defined as the date of the first claim for an antipsychotic drug after a claim for the underlying disorder but before TD diagnosis.

The selected prediction model had a clinically meaningful concordance of 70% and was well calibrated. The researchers identified four treatment characteristics associated with TD. Patient’s age at index date, diagnosis of schizophrenia, dosage of antipsychotic at index date (up to 100 mg/day chlorpromazine equivalent), and presence of bipolar and related disorders were significantly associated with an increased risk of TD diagnosis. In addition, the use of atypical antipsychotics at index date was associated with a modest reduction in the risk of TD.

In conclusion, the researchers stated: “This study identified a group of factors associated with the development of tardive dyskinesia among patients with psychiatric disorders treated with antipsychotics. This may allow physicians to better monitor their patients receiving antipsychotics, allowing for the prompt identification and treatment of tardive dyskinesia to help maintain quality of life.”

Various strategies have been examined to reduce the cumulative exposure to antipsychotics, including dose reduction, intermittent dosing strategies, such as drug holidays, and antipsychotic cessation. A 

 included 13 randomized controlled trials with 711 participants to examine antipsychotic reduction and/or cessation and antipsychotics as specific treatments for TD.

 However, limited data from the small studies using antipsychotic reduction or specific antipsychotic drugs as treatments for TD did not provide any convincing evidence of the value of these approaches.

1. Patterson-Lomba O, Ayyagari R, Carroll B. 

62 Predictors of Tardive Dyskinesia in Psychiatric Patients Taking Concomitant Antipsychotics

2. Bergman H1, Rathbone J, Agarwal V, Soares-Weiser K. 

Antipsychotic reduction and/or cessation and antipsychotics as specific treatments for tardive dyskinesia

A prediction model may help identify treatment characteristics associated with TD among patients with psychiatric disorders taking antipsychotic medications.

Advances in Predicting Tardive Dyskinesia

Persons taking any kind of antipsychotic medication need to be monitored for movement disorders. The AIMS (

) aids in the early detection of tardive dyskinesia as well as providing a method for on-going surveillance.

Although the incidence of TD has been relatively low in recent years, changes in prescribing may result in increased occurrence. Clinicians will need to be alert to these possibilities and employ tools that will help them pick up developing problems as soon as possible.

This simple checklist takes only 10 minutes to complete and uses a 5-point rating scale for recording scores for 7 body areas: face, lips, jaw, tongue, upper extremities, lower extremities, and trunk.

An instructional video has been created to show how to conduct the AIMS examination and how to score the findings. Dr. Jay Pomerantz demonstrates each step of the AIMS procedure. With the help of a "standardized patient", he also shows what the different levels of symptom severity look like and explains how they should be scored.
	
	It is suggested that you download and print out the AIMS Form and the AIMS Instructions before viewing the Instructional Video so that you will be able to follow along on each step of the examination and the scoring of the abnormal movements.
	
	Downloading and printing out the 

 also in advance of viewing the video will give you a complete description of the information on the video and the length of time of each segment so you can skip forward and back.

These scales are easily used online and via mobile devices for assessment at the point of care. Score, share and record results.

The Program Guide for AIMS Instructional Video

This article was originally published on April 1, 2013, and has since been updated. -ED.

This video will help clinicians detect tardive dyskinesia and movement disorders in patients taking antipsychotic drugs.

Tardive Dyskinesia