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Major risk factors for onset of tardive dyskinesia are considered.

PsychQuiz: Tardive Dyskinesia Risk Factors

What major challenges do patients with tardive dyskinesia face in their daily lives? Take the quiz and learn more.

PsychQuiz: Consequences of Tardive Dyskinesia

The first study to use social media listening (SML) analysis of unsolicited patient and caregiver insights might give a better look into the perspective of patients with tardive dyskinesia (TD).

TD, a difficult movement disorder, is commonly associated with prolonged exposure to dopamine receptor blocking agents such as antipsychotics. Based on gathered data, it also has a number of patients left feeling unheard.

“Because the emotions and sentiments of patients (and sometimes caregivers) on social media platforms are unsolicited and unfiltered, SML methods… offer a more comprehensive context for understanding how patients experience TD and the unmet needs in this therapeutic space,” Farrar et al. wrote in their discussion. “As indicated in the recent FDA guidance on patient engagement for drug development,

 social media can allow access to difficult-to-reach populations, provide accurate and automatic capture of data, and possibly result in greater self-disclosure by patients.”

For this pilot study, researchers collected patient insights from 261 social media posts made by patients and caregivers, mainly on blog forums and Twitter, using predefined search terms. Of the 261 posts, 107 were used for analysis. Overall, the sentiments leaned negative, with 64% responses being negative, 33% neutral, and only 3% positive.

Three themes emerged: anger, insecurity, and symptoms. Common sentiments showed patients were angry about developing TD from a medication used to treat another of their conditions, insecure about feeling unaccepted by society, and afraid of being judged.

All posts were gathered from publicly available, nonpassword protected sites. In order to protect the identity of users, all personal information was excluded prior to any manual review of the content and verbatim quotes were not included in the final report.

While researchers admitted that the study might be limited by a small sample size and reliance on self-reporting, they concluded social media may help convey unmet patient needs that do not get addressed in clinical discussions.

1. Farrar M, Lundt L, Franey E, Yonan C. Patient perspective of tardive dyskinesia: results from a social media listening study. 

2. US Food and Drug Administration. Patient-focused drug development: collecting comprehensive and representative input guidance for industry, Food and Drug Administration staff, and other stakeholders. Center for Drug Evaluation and Research; 2020.

The first study to gather unsolicited patient responses via social media finds 3 negative themes. 

Patients With Tardive Dyskinesia Feel Unheard, Social Media Listens

John J. Miller, MD, talks about the increased risk of tardive dyskinesia on a synaptic level.

is medical director, Brain Health, Exeter, NH; editor in chief,

; staff psychiatrist, Seacoast Mental Health Center, Exeter, NH; consulting psychiatrist, Exeter Hospital, Exeter, NH; consulting psychiatrist, Insight Meditation Society, Barre, MA.

How could drugs that block post-synaptic dopamine 2 receptors increase the risk for tardive dyskinesia overtime? 

Increased Risk of Tardive Dyskinesia 

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.

Tardive Dyskinesia