Treatment Of Tardive Dyskinesia Research Articles

Prevalence of Tardive Dyskinesia in an Electronic Medical Record Study at a Large Community Mental Health Treatment Center.

Objective: To determine the prevalence of tardive dyskinesia (TD) identified by clinicians in naturalistic data in a real-world treatment setting.Methods: Electronic medical record data were analyzed from a single large community mental health treatment center for all psychiatric provider encounters of 120,431 unique adult and child patients during a 5-year period from January 2013 through December 2017, focusing on clinician-identified TD in patients prescribed antipsychotic medication.Results: Only half of the antipsychotic-prescribed patients had Abnormal Involuntary Movement Scale (AIMS) information recorded in their medical records, and only 1% of those with AIMS data had a positive AIMS identifying TD. AIMS testing represented the largest source of all identified TD in these patients, but only one-third of the patients with a positive AIMS in the record had a clinical diagnosis of TD recorded in the prescriber's diagnostic impression list from billing code data. The clinical identification of only 1% of antipsychotic-prescribed patients with TD in this study is far below generally established TD prevalence estimates of previous research. An important methodological contributor to this discrepancy is generation of the data by treating clinicians in this study who greatly under identified TD relative to systematic research methodology.Conclusions: Given the recent availability of US Food and Drug Administration-approved pharmaceutical agents for treatment of TD, it is now more important than ever to identify and intervene in TD. Agency-wide policies and procedures can be established to ensure that TD assessments are systematically conducted with regularity and accuracy among all antipsychotic-prescribed patients.

Late-Onset Dyskinesia Occurring During Antipsychotic Treatment for Schizophrenia: Treatments for Tardive Dyskinesia

Tardive dyskinesia is recognized as buccolingual dyskinesia, but also includes various involuntary movements, such as chorea, dystonia, myoclonus, and tremor. Tardive dyskinesia can be treated depending on the type of movement disorder present. Antipsychotics causing tardive dyskinesia should be reduced in dosage or should be discontinued. However, the treatment of schizophrenia is important, and neurologists must treat tardive dyskinesia in collaboration with psychiatrists taking care of patients with tardive dystonia. Various treatments, such as VMAT-2 inhibitors or tetrabenazine, reserpine, dopamine receptor antagonists, botulinum toxin therapy, anticholinergic agents, or deep brain stimulation, are trialed, depending on the type of movement disorder and the degree of severity of the disorder.

Once-Daily Valbenazine Is Effective for Tardive Dyskinesia in Elderly Patients (>=65 Years)

<h3>Introduction</h3> Valbenazine is a selective and potent vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD), a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics or other dopamine-receptor blocking agents (DRBAs). Valbenazine is the only approved TD medication with once-daily dosing and no requirements or cautions for dosing based on age. Older adults (≥55 years) have an increased risk for TD after a shorter duration of treatment with DRBAs, and previous analyses have shown that valbenazine is effective and well tolerated in this population (Sajatovic et al, Int J Geriatr Psychiatry 2020). The current presentation includes findings from the first analyses to evaluate the effects of an approved TD medication in an elderly population, using the more conventional age cutoff of ≥65 years. <h3>Methods</h3> Data from two long-term studies (KINECT 3-extension, KINECT 4) of participants receiving up to 48 weeks of once-daily treatment with valbenazine (40 mg or 80 mg) were pooled and analyzed by age (≥65 and <65 years). Analyses included mean change from baseline (CFB) to Week 48 in Abnormal Involuntary Movement Scale (AIMS) total score. AIMS response at Week 48 was also assessed as follows: clinically meaningful response (≥30% improvement from baseline); protocol-defined response (≥50% improvement from baseline). Additional analyses included response thresholds for Clinical Global Improvement-Tardive Dyskinesia (CGI-TD) and Patient Global Impression of Change (PGIC) as follows: rating of "minimally improved" or better (score ≤3) at Week 48 (CGI-TD≤3, PGIC≤3); rating of "much improved" or "very much improved" (score ≤2) at Week 48 (CGI-TD≤2, PGIC≤2). Treatment-emergent adverse events (TEAEs) were also monitored. <h3>Results</h3> Treatment outcomes were generally robust and comparable between the age subgroups. Pooled AIMS results indicated substantial improvements in TD movements were found in both age subgroups with valbenazine 40 mg (≥65 years, n=8; <65 years, n=46) and 80 mg (≥65 years, n=20; <65 years, n=105): mean CFB (≥65 years, -6.4 and -9.8 [for 40 and 80 mg, respectively]; <65 years, -5.5 and -8.3); clinically meaningful ≥30% response (≥65 years, 75% and 95%; <65 years, 61% and 80%); and protocol-defined ≥50% response (≥65 years, 75% and 85%; <65 years, 50% and 70%). CGI-TD and PGIC response rates indicated that clinician- and patient-reported global improvements were also substantial in both age subgroups: CGI-TD≤3 (≥65 years, 88% and 100% [for 40 and 80 mg, respectively]; <65 years, 89% and 97%); CGI-TD≤2 (≥65 years, 88% and 95%; <65 years, 62% and 83%); PGIC≤3 (≥65 years, 88% and 100%; <65 years, 89% and 94%); PGIC≤2 (≥65 years, 75% and 90%; <65 years, 77% and 80%). Analyses of TEAEs indicated no statistically significant differences between age subgroups for the incidence of any TEAEs (≥65 years, 73%; <65 years, 72%) or any serious TEAEs (≥65 years, 18%; <65 years, 17%). However, discontinuations due to TEAEs were significantly more common in elderly participants (≥65 years, 26%; <65 years, 13%; <i>P</i><0.05). <h3>Conclusions</h3> These analyses, which are the first to evaluate any approved TD medication in patients ≥65 years, indicate that long-term treatment with once-daily valbenazine is appropriate and beneficial for this age group. Elderly study participants had clinically meaningful and substantial improvements in TD that were comparable to (or better than) those in the younger cohort. These results may provide clinicians with important information about the management of TD in elderly patients. <h3>This research was funded by</h3> Neurocrine Biosciences, Inc.

Long-Term Deutetrabenazine Treatment for Tardive Dyskinesia Is Associated With Sustained Benefits and Safety: A 3-Year, Open-Label Extension Study.

BackgroundDeutetrabenazine is a vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal studies, deutetrabenazine demonstrated statistically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores, with favorable safety/tolerability in TD patients. This study reports long-term efficacy and safety of deutetrabenazine in a 3-year, single-arm, open-label extension (OLE) study.MethodsPatients who completed the pivotal studies could enroll in this single-arm OLE study, titrating up to 48 mg/day based on dyskinesia control and tolerability. Efficacy was assessed based on change from baseline in total motor AIMS score, Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC), and quality of life (QOL) assessments. Safety evaluation included adverse event (AE) incidence, reported using exposure-adjusted incidence rates, and safety scales.Results343 patients enrolled in the study (6 patients were excluded). At Week 145 (mean dose: 39.4 ± 0.83 mg/day), mean ± SE change from baseline in total motor AIMS score was −6.6 ± 0.37 and 67% of patients achieved ≥50% improvement in total motor AIMS score. Based on CGIC and PGIC, 73% and 63% of patients achieved treatment success, respectively. QOL improvements were also observed. Deutetrabenazine was generally well tolerated, with low rates of mild-to-moderate AEs and no new safety signals; most safety scales remained unchanged over time.ConclusionsLong-term deutetrabenazine treatment was associated with sustained improvement in AIMS scores, indicative of clinically meaningful long-term benefit, and was generally well tolerated. Results suggest deutetrabenazine may provide increasing benefit over time without increases in dose.

Defining utility values for patients with tardive dyskinesia

Objective To measure health state preferences and estimate utility values for tardive dyskinesia (TD) from the perspective of the US general population, accounting for factors affecting quality of life (QOL). Methods Participants from the general population were recruited and asked to watch and assess videos of professional actors simulating nine health states, including psychiatric disorders with/without TD and moderate-to-severe TD without any underlying disease. Time tradeoff (TTO) methods were used to elicit utility values, which ranged from −1 (worse than death) to +1 (perfect health) and represented individual preferences for avoiding specific health states associated with TD. Lower TTO utility values indicated individuals’ willingness to give up more years of life to avoid living in each health state. Results Based on TTO responses (n = 157), mean ± standard deviation utility for TD alone was 0.59 ± 0.38. Mean utilities for schizophrenia with negative symptoms (without TD: 0.43; with TD: 0.29) and positive symptoms (without TD: 0.44; with TD: 0.30) were generally lower than those for bipolar disorder (without TD: 0.59; with TD: 0.46) and major depressive disorder (without TD: 0.60; with TD: 0.44). According to utility decrements associated with TD (0.13–0.16), respondents were willing to give up 1.3 to 1.6 years during a 10-year lifespan to avoid living with TD. Conclusions Utility decrements for TD in this study were slightly larger than previously reported values, potentially due to incorporation of QOL and social consequences in TD health state descriptions. An important limitation of this analysis is that participants’ willingness to trade future years of healthy life may not indicate actual willingness to accept the life decrement. These findings can be leveraged to improve cost-effectiveness analyses used to assess the value of treatments for TD.

Progress in diagnosis and treatment of delayed movement disorder

Delayed movement disorder is an involuntary movement syndrome after long-term use of antipsychotic drugs, and also a serious adverse drug reaction. The treatment of delayed movement disorder has been an important issue. How to carry out related prevention is directly related to the vital interests of patients. This article reviews the etiology, pathogenesis, clinical features, diagnosis and treatment of tardive dyskinesia. Keywords: delayed movement disorder; diagnosis; treatment.

Vitamin E in the treatment of tardive dyskinesia: a meta-analysis.

Long-term use of antipsychotic drugs is associated with tardive dyskinesia. At present, there is no satisfactory treatment for tardive dyskinesia. Some randomized trials suggested that vitamin E can improve tardive dyskinesia. This study was undertaken to evaluate the effects of vitamin E treatment for tardive dyskinesia. We searched internet databases for randomized controlled trials. A total of 21 studies including 854 patients with tardive dyskinesia were included in this meta-analysis. Eighteen studies reported the Abnormal Involuntary Movements Scale (AIMS) as the primary outcome. After vitamin E treatment, a decrease of 2.36 (95% CI = -3.27 to -1.45; P < 0.00001) in the AIMS was observed in the treatment group, compared with the control group. Vitamin E may offer a new avenue treatment for tardive dyskinesia.

Pathophysiology, prognosis and treatment of tardive dyskinesia.

Tardive dyskinesia (TD), a movement disorder associated with antipsychotics, most frequently affects the lower face and jaw muscles, but can also affect walking, breathing and use of the hands and limbs. Knowledge of TD among physicians may be limited, and the pathophysiology of TD is poorly understood. We conducted this review to summarise the current knowledge surrounding the pathophysiology of TD and present recommendations for prevention and treatment based on a literature search and roundtable discussion attended by psychiatrists in Japan. It has been suggested that dopamine hypersensitivity, damaged gamma-aminobutyric acidergic neurons and/or increased production of reactive oxygen species may contribute to development of TD. Symptoms can profoundly affect everyday life; patients who develop TD have poorer prognoses, worse health-related quality of life, greater social withdrawal and higher mortality than patients without TD. Traditional treatment options include dietary supplements, although evidence for their effectiveness is low. Among pharmaceutical interventions, there is moderate evidence that switching to the second-generation antipsychotic clozapine, which has a lower affinity for dopamine D2 receptors than other antipsychotics, may improve symptoms. Vesicular monoamine transporter 2 (VMAT-2) inhibitors, which oppose the increased dopaminergic activity associated with prolonged antipsychotic use by interfering with dopamine uptake and storage, have the strongest evidence for efficacy. VMAT-2 inhibitors are approved in the United States for the treatment of TD, and the first VMAT-2 inhibitor was approved in Japan for this indication in March 2022. Most guidelines recommend treating TD by first reducing the dose of antipsychotics or switching to clozapine or other second-generation antipsychotics, which have a lower association with TD than first-generation antipsychotics. We recommend focusing on prevention and monitoring for TD when prescribing antipsychotics, given that TD is often irreversible. Physicians should treat with antipsychotics only when necessary and at the lowest effective dose, and frequently monitor for TD symptoms.Plain Language Summary Plain Language Summary (In Japanese) Visual Summary Visual Summary (In Japanese)

Celebrating 10 years of the Journal of Comparative Effectiveness Research.

Celebrating 10 years of the Journal of Comparative Effectiveness Research.

(+)-9-Trifluoroethoxy-α-Dihydrotetrabenazine as a Highly Potent Vesicular Monoamine Transporter 2 Inhibitor for Tardive Dyskinesia.

Valbenazine and deutetrabenazine are the only two therapeutic drugs approved for tardive dyskinesia based on blocking the action of vesicular monoamine transporter 2 (VMAT2). But there exist demethylated inactive metabolism at the nine position for both them resulting in low availability, and CYP2D6 plays a major role in this metabolism resulting in the genetic polymorphism issue. 9-trifluoroethoxy-dihydrotetrabenazine (13e) was identified as a promising lead compound for treating tardive dyskinesia. In this study, we separated 13e via chiral chromatography and acquired R,R,R-13e [(+)-13e] and S,S,S-13e [(−)-13e], and we investigated their VMAT2-inhibitory activity and examined the related pharmacodynamics and pharmacokinetics properties using in vitro and in vivo models (+)-13e displayed high affinity for VMAT2 (Ki = 1.48 nM) and strongly inhibited [3H]DA uptake (IC50 = 6.11 nM) in striatal synaptosomes. Conversely, its enantiomer was inactive. In vivo, (+)-13e decreased locomotion in rats in a dose-dependent manner. The treatment had faster, stronger, and longer-lasting effects than valbenazine at an equivalent dose. Mono-oxidation was the main metabolic pathway in the liver microsomes and in dog plasma after oral administration, and glucuronide conjugation of mono-oxidized and/or demethylated products and direct glucuronide conjugation were also major metabolic pathways in dog plasma. O-detrifluoroethylation of (+)-13e did not occur. Furthermore, CYP3A4 was identified as the primary isoenzyme responsible for mono-oxidation and demethylation metabolism, and CYP2C8 was a secondary isoenzyme (+)-13e displayed high permeability across the Caco-2 cell monolayer, and it was not a P-glycoprotein substrate as demonstrated by its high oral absolute bioavailability (75.9%) in dogs. Thus, our study findings highlighted the potential efficacy and safety of (+)-13e in the treatment of tardive dyskinesia. These results should promote its clinical development.

Measurement-based Diagnosis and Treatment for Tardive Dyskinesia

Tardive dyskinesia (TD) is an involuntary movement disorder associated with agents that block dopamine receptors, particularly antipsychotics. TD commonly involves the orofacial muscles and extremities, and, because these movements are out of the patient's control, they can have serious physical and psychological effects. An accurate and early diagnosis of TD is crucial because the risk of permanence increases over time. To minimize the risk of TD development, clinicians should use the lowest necessary doses of dopamine receptor blocking agents, and, if allowed by the treated condition, the dopamine receptor blocking agents should be stopped after the shortest necessary time. Clinicians should try to avoid parkinsonian adverse effects and akathisia and prefer second-generation antipsychotics over first-generation antipsychotics. Moreover, clinicians should differentiate between TD and other drug-induced movement disorders, particularly drug-induced parkinsonism, as anticholinergic treatment can worsen TD. To facilitate measurement-based care, clinicians should use the Abnormal Involuntary Movement Scale examination to screen for and routinely monitor TD, especially when providing treatments intended to decrease the symptoms and impact of TD. Two vesicular monoamine transporter-2 (VMAT2) inhibitors, deutetrabenazine and valbenazine, are approved by the US Food and Drug Administration to treat TD. For patients who have moderate to severe or disabling TD, the American Psychiatric Association recommends treatment with the VMAT2 inhibitors. Clinicians should communicate with patients and care partners about risk factors for and signs of TD, as well as available treatment options for TD and what they can expect in terms of short- and long-term results.

Valbenazine for the Treatment of Adults with Tardive Dyskinesia.

This a comprehensive review of the literature regarding the use of Valbenazine in treating tardive dyskinesia. A primarily oral movement disorder induced by chronic exposure to certain classes of medications, tardive dyskinesia is often resistant to many therapeutic approaches. This review presents the background, evidence, and indications for the use of Valbenazine as a treatment option for this condition. Tardive dyskinesia is a disorder arising from long-term exposure to medications that blocked dopamine receptors, primarily antipsychotics. It is characterized by abnormal movements of the oral-buccal-lingual structures as well as associated pain and hypertrophy. Simply stopping the use of the dopamine blocking agents effectively alleviates the symptoms but is not always reliable hence the need for another therapeutic approach.Valbenazine is thought to function as a highly selective inhibitor of the VMAT2 vesicular monoamine transporter resulting in decreased availability of dopamine in the presynaptic cleft. This leads to decreased dopaminergic activation of the striatal motor pathway. The FDA approved Valbenazine in 2017 to treat tardive dyskinesia in adults and needs to be evaluated with existing therapeutic approaches. The chronic use of dopamine receptor blocking agents, most commonly antipsychotics, can lead to a movement disorder called tardive dyskinesia. Once symptom onset has occurred, these movement abnormalities can persist for years to permanently, depending on the speed and effectiveness of treatment. Valbenazine is a relatively newer option for the treatment of tardive dyskinesia in adults. Compared to other pharmaceutical agents, it is more selective and has limited toxicities making it an effective treatment regimen. However, further research, including additional direct comparison studies, should be conducted to fully evaluate this drug's usefulness.

Electroconvulsive Therapy as a Treatment for Tardive Dyskinesia.

To review the published literature over the last 10 years for the use of electroconvulsive therapy (ECT) in tardive dyskinesia (TD), focusing on the efficacy of this treatment. A comprehensive evidence search of the published literature in the last 10 years (2010-2020) was conducted using the search terms electroconvulsive therapy, electroshock therapy, ECT, tardive dyskinesia, and tardive dystonia. The review was limited to articles published in the English language. MEDLINE, Embase, PubMed, PsycInfo, Cochrane Library, Google Scholar, and the NICE (National Institute for Health and Care Excellence) guidelines were also searched. Twenty-three case studies published within the last 10 years were retrieved. The search revealed 5 articles of potential relevance. The articles were analyzed by both authors to obtain clinical information relevant to meeting the objectives of the review. The efficacy in using ECT for TD is derived only from case series and case reports. There were no controlled trials, and the evidence collated was limited and of low quality. The review indicates that ECT could be considered as a treatment for TD. However, this treatment may only be considered when patients present with a coexistent refractory mood or affective disorder. Further clinical trials are needed to improve understanding regarding the efficacy, tolerability, and safety of using ECT in this patient group.

Incidence of Adverse Events Associated With Deutetrabenazine for the Treatment of Tardive Dyskinesia and Chorea Associated With Huntington’s Disease (4416)

Incidence of Adverse Events Associated With Deutetrabenazine for the Treatment of Tardive Dyskinesia and Chorea Associated With Huntington’s Disease (4416)

Tardive Dyskinesia: Assessing and Treating a Debilitating Side Effect of Prolonged Antipsychotic Exposure

Tardive Dyskinesia: Assessing and Treating a Debilitating Side Effect of Prolonged Antipsychotic Exposure

Development of a RP-HPLC Method for Separating and Quantifying Muscimol in Different Developmental Stages of the Fungus Amanita muscaria

A simple RP-HPLC method was designed for the quantification of muscimol (5-(aminomethyl)-isoxazol-3-ol) present in five aqueous extracts of Amanita muscaria each from a different developmental stage. Results show that the maximum concentration of muscimol (1,210 mg/ml) was found in the young mushroom stage of development. Moreover, it was also found that this concentration progressively decreases as the fungus ages. The developed method is a simple but effective method for the quantification of muscimol, a widely important metabolite for the pharmaceutical industry as a possible treatment for tardive dyskinesia and Parkinson’s disease.

Differentiating tardive dyskinesia: a video-based review of antipsychotic-induced movement disorders in clinical practice.

Accurate diagnosis and appropriate treatment of tardive dyskinesia (TD) are imperative, as its symptoms can be highly disruptive to both patients and their caregivers. Misdiagnosis can lead to incorrect interventions with suboptimal or even deleterious results. To aid in the identification and differentiation of TD in the psychiatric practice setting, we review its clinical features and movement phenomenology, as well as those of other antipsychotic-induced movement disorders, with accompanying links to illustrative videos. Exposure to dopamine receptor blocking agents (DRBAs) such as antipsychotics or antiemetics is associated with a spectrum of movement disorders including TD. The differential diagnosis of TD is based on history of DRBA exposure, recent discontinuation or dose reduction of a DRBA, and movement phenomenology. Common diagnostic challenges are the abnormal behaviors and dyskinesias associated with advanced age or chronic mental illness, and other movement disorders associated with DRBA therapy, such as akathisia, parkinsonian tremor, and tremor related to use of mood stabilizing agents (eg, lithium, divalproex). Duration of exposure may help rule out acute drug-induced syndromes such as acute dystonia or acute/subacute akathisia. Another important consideration is the potential for TD to present together with other drug-induced movement disorders (eg, parkinsonism, parkinsonian tremor, and postural tremor from mood stabilizers) in the same patient, which can complicate both diagnosis and management. After documentation of the phenomenology, severity, and distribution of TD movements, treatment options should be reviewed with the patient and caregivers.

How to Assess Tardive Dyskinesia Symptom Improvement With Measurement-Based Care.

​​​​​​ Clinicians now have 2 effective and well-tolerated vesicular monoamine transporter 2 (VMAT2) inhibitors-valbenazine and deutetrabenazine-for the treatment of patients with tardive dyskinesia (TD), a severe and potentially irreversible side effect associated with dopamine receptor blocking agents. Clinicians should use measurement-based care, eg, the Abnormal Involuntary Movement Scale with activation maneuvers, to assess and document TD symptoms and treatment progress. Each follow-up visit should be personalized with questions related to patients' functioning and level of distress regarding their specific TD symptoms. Family members, if available, can provide information on symptom changes and assistance with medication adherence. With continued treatment and measurement-based care, patients can experience improvement in their TD symptoms.

Real-world evaluation of patient characteristics and disease management in long-term valbenazine treatment in adults with Tardive dyskinesia

Objectives: Tardive dyskinesia (TD) is a persistent and often disabling involuntary movement disorder that is associated with long-term exposure to dopamine receptor blocking agents (DRBAs) such as antipsychotics. The long-term efficacy of INGREZZA® (valbenazine) capsules, which was approved in 2017 for treating TD in adults, has been demonstrated in several prospective clinical trials. This multi-center, retrospective chart review will assess the clinical characteristics and overall disease management of adult patients receiving long-term valbenazine treatment for TD in a real-world setting.

Chart extraction/clinician survey shows symptom impact and favorable treatment outcomes with VMAT2 inhibitors in patients with Tardive dyskinesia

Objective: Based on clinical studies for two approved vesicular monoamine transporter 2 (VMAT2) inhibitors (valbenazine, deutetrabenazine), these medications are recommended as first-line therapies for tardive dyskinesia (TD). Real-world data for these drugs are now available. The objective of this study was to describe symptom impact and treatment outcomes in patients prescribed VMAT2 inhibitors for the treatment of TD.