Gastroparesis treatment options metoclopramide and prucalopride: analysis of the FDA Adverse Event Reporting System (FAERS) database.

BACKGROUND: We aimed to examine the common adverse drug reactions (ADRs) of metoclopramide, FDA-approved for treating many gastrointestinal conditions including gastroparesis, and prucalopride, FDA-approved for treating chronic idiopathic constipation but used off-label for other gastrointestinal conditions including gastroparesis. RESEARCH DESIGN AND METHODS: The FDA Adverse Event Reporting System (FAERS) was analyzed from January 2013 to December 2023. ADR reports regarding use of only metoclopramide or prucalopride were analyzed following exclusion of reports indicating use for treatment of non-gastrointestinal conditions. RESULTS: Analysis of 1,085 reports on metoclopramide revealed tardive dyskinesia (n = 393, 36.2%) and dystonia (n = 170, 15.7%) among the most reported ADRs in addition to QTc prolongation (n = 16, 1.5%) with progression to Torsade de pointes (n = 5, 0.5%) and triggering of pheochromocytoma crisis (n = 24, 2.2%). Analysis of 865 reports on prucalopride revealed headache (n = 120, 13.9%), diarrhea (n = 116, 13.4%), and abdominal pain (n = 100, 11.6%) as the most common ADRs with 22 reports (2.5%) of dystonia with the use of prucalopride. CONCLUSIONS: This FAERS database analysis shows post-marketing reports of ADRs from metoclopramide most frequently include tardive dyskinesia, dystonia, and tremor in addition to potentially fatal arrhythmias such as Torsade de pointes. Consumers of prucalopride may also be at risk of dystonia and other ADRs.

Efficacy and safety of different pharmacological interventions in the treatment of tardive dyskinesia: a systematic review and network meta-analysis.

OBJECTIVES: The aim of this study is to indirectly compare and rank the different drugs that have been studied in randomized clinical trials (RCTs) in patients with tardive dyskinesia (TD) in terms of their efficacy in ameliorating the symptoms of TD and safety. DESIGN: A network meta-analysis and a systematic review were registered prospectively on PROSPERO under the ID: CRD42023407823 and were conducted in accordance with the PRISMA-NMA guidelines. DATA SOURCES: PubMed, Scopus, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Sciences, and Clinicaltrials.gov were searched to identify relevant records. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Any parallel randomized blinded controlled clinical trials that studied the use of any medications in treating TD and assessed the symptoms using a functional scale that has been previously validated. DATA EXTRACTION: The standardized mean difference of improvement along with the reported adverse events for each drug was extracted from each trial, and a network meta-analysis was conducted using a random-effects model. RESULTS: One thousand eight hundred seventeen patients in 33 RCTs were included in the analysis. Twenty-three different drugs were compared to placebo in terms of reduction in TD symptoms. Among these, valbenazine 80 mg (SMD = - 1.66, 95%CI = [- 2.55; - 0.78]), valbenazine 40 mg (- 1.00, [- 1.89; - 0.11]), and vitamin E (- 0.77, [- 1.45; - 0.1]) significantly reduced TD symptoms in comparison to placebo, while deutetrabenazine 36 mg (- 1.00, [- 2.12; 0.11]) and reserpine (- 0.54, [- 1.09; 0.02]) did not significantly reduce symptoms. Some serious adverse events were reported for valbenazine and deutetrabenazine, which included mainly psychiatric symptoms such as depression, worsening of schizophrenia, and suicidal ideation, while mild adverse events were reported for other drugs, and their incidence in the treatment arms was comparable to those in the placebo arm. CONCLUSIONS: Valbenazine (80 and 40 mg) and vitamin E demonstrated efficacy in treating tardive dyskinesia. However, the significant side effects of valbenazine should prompt further investigation of alternative treatment modalities.

A Model-Informed Drug Development Approach Supporting the Approval of an Unstudied Valbenazine Dose for Patients With Tardive Dyskinesia.

Valbenazine is a highly potent and selective inhibitor of synaptic vesicular monoamine transporter 2. The current therapeutic doses of valbenazine for tardive dyskinesia (TD) are 40, 60, or 80 mg capsules, given orally, once daily (QD). While 40 and 80 mg were investigated in phase 3 KINECT® 3 trial and initially approved, the approval of valbenazine 60 mg was based on the analysis utilizing the Model-informed drug development (MIDD) approach, facilitated through the US Food and Drug Administration's MIDD Pilot Program. This study aimed to demonstrate the efficacy of 60 mg QD dose through model simulations using an established exposure-response (E-R) relationship between valbenazine active metabolite [+]-α-dihydrotetrabenazine exposure and the change from baseline in Abnormal Involuntary Movement Scale total score (AIMS-CFB). A longitudinal E-R model was constructed based on the 40 and 80 mg data from the KINECT 3 trial. The final Emax model adequately predicted dose-dependent improvement in the primary endpoint and was used to interpolate AIMS-CFB for 60 mg at week 6. The efficacy of the unstudied 60 mg dose regimen is expected to be within the range of doses studied clinically with predicted mean AIMS-CFB (95% confidence interval) of -2.69 (-3.30, -2.13) between observed mean AIMS-CFB for 40 mg of -1.92 and 80 mg of -3.39. Results from this analysis provided the key evidence to establish efficacy of 60 mg QD without the need for an additional clinical trial. The availability of valbenazine 60 mg dose fills an existing medical need for patients with TD who could benefit from this third effective dose.

Transcranial direct current stimulation improves tardive dyskinesia in long-term hospitalized patients with chronic schizophrenia.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of transcranial direct current stimulation (tDCS) in chronic schizophrenia patients with tardive dyskinesia (TD) who were long-term hospitalized. METHODS: Sixty-four inpatients who met the DSM-IV diagnostic criteria for schizophrenia and TD were randomly assigned to either the active (N=35) or sham (N=29) group. Treatment was given 15 times, with each session lasting for 30 min, and an intensity of 2 mA. The anode was placed on the left dorsolateral prefrontal cortex and the cathode on the right supraorbital region. Primary outcome was measured by the changes in Abnormal Involuntary Movements Scale (AIMS) score. Secondary outcomes were measured using the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). Adverse effects of tDCS were assessed with an experimenter-administered open-ended questionnaire throughout the experiment. RESULTS: Of the 64 patients, 52 (81.25%) completed the study. Compared to the sham group, patients in the active group exhibited a significant reduction in both the total AIMS score and the facial-oral subscore (P<0.05). An improvement of at least 30% in total AIMS scores was observed in the active group (14 patients, 50%) compared to the sham group (2 patients, 8.3%) after treatment (P<0.01). There were no between-group differences in the PANSS and SANS total scores. However, there was a significant difference between the two groups in the occurrence of the reported adverse effect of tingling sensation (P<0.05). CONCLUSIONS: TDCS may be an effective and safe treatment for improving the facial-oral motor symptoms of TD in chronically hospitalized patients with schizophrenia. SIGNIFICANCE: This study provides a novel perspective for the clinical treatment of patients with TD.

Profiling deutetrabenazine extended-release tablets for tardive dyskinesia and chorea associated with Huntington's disease.

INTRODUCTION: Tardive dyskinesia (TD) and Huntington's disease (HD)-associated chorea are persistent and disabling hyperkinetic disorders that can be treated with vesicular monoamine transporter type 2 (VMAT2) inhibitors, including the recently approved once-daily (QD) formulation of deutetrabenazine (DTBZ ER). While its efficacy and safety profile have not been directly investigated, currently available data confirms bioequivalence and similar bioavailability to the twice-daily formulation (DTBZ BID). AREAS COVERED: The authors briefly review the pivotal trials establishing efficacy of DTBZ for TD and HD-associated chorea, the pharmacokinetic data for bioequivalence between QD and BID dosing of DTBZ, as well as dose proportionality evidence, titration recommendations, and safety profile for DTBZ ER. EXPERT OPINION: Long-term data show that DTBZ is efficacious and well tolerated for the treatment of TD and HD-associated chorea. DTBZ ER likely demonstrates therapeutic equivalence with no new safety signals. Due to the lack of comparative clinical trial data, no evidence-based recommendation about choice of VMAT2 inhibitor or switching between VMAT2 inhibitors can be made about best practice. Ultimately, QD dosing may offer the chance of improved medication adherence, an important consideration in patients with complex treatment regimens and/or patients with cognitive decline.

A Case of Oral-Buccal-Lingual Dyskinesia and Neuropsychiatric Symptoms After Prolonged Levetiracetam Exposure.

Tardive dyskinesia (TD) is a serious and often permanent complication usually seen after the long-term use of antipsychotic medications, and multiple other classes of medications have been reported to cause TD or TD-like syndromes. TD can affect any part of the body, but it most commonly affects the mouth, lips, and tongue. We present a case of oral-buccal-lingual dyskinesia in an 86-year-old female from the long-term use of levetiracetam for a seizure disorder. The patient was started on levetiracetam four years before admission and was noted to have an acute onset of oral-buccal-lingual dyskinesia that was so severe it interrupted the patient's speech and feeding. The patient's dyskinesias are completely resolved after cross-tapering levetiracetam 500 mg twice a day with valproic acid 750 mg daily. Additionally, there was a global recovery of the patient's mood and psychosis after the cross-taper. Our case highlights the potential implications of levetiracetam in dyskinetic movements and neuropsychiatric symptoms, and it warrants close monitoring of patients taking this medication especially elderly with multiple comorbidities and compromised renal function. Moreover, the case suggests the reversible nature of both neuropsychiatric symptoms and dyskinesias.

Ginkgo biloba for Tardive Dyskinesia and Plasma MnSOD Activity: Association with MnSOD Ala-9Val Variant.

BACKGROUND: Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype. METHODS: An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded sample, we compared MnSOD activity in 159 TD, 227 non-TD and 280 healthy controls, as well as the allele frequencies and genotypes for the MnSOD Ala-9Val polymorphism in 352 TD, 486 non-TD and 1150 healthy controls. RESULTS: EGb761 significantly reduced TD symptoms and increased MnSOD activity in TD patients compared to placebo (both p < 0.01). Moreover, we found an interaction between genotype and treatment response (p < 0.001). Furthermore, in the EGb761 group, patients carrying the Ala allele displayed a significantly lower AIMS total score than patients with the Val/Val genotype. In addition, MnSOD activity was significantly lower at baseline in TD patients compared with healthy controls or non-TD patients. CONCLUSION: EGb761 treatment enhanced low MnSOD activity in TD patients and produced greater improvement in TD symptoms in patients with the Ala allele of the MnSOD Ala-9Val polymorphism.

Immunosenescence-related T cell phenotypes and white matter in schizophrenia patients with tardive dyskinesia.

Schizophrenia patients with tardive dyskinesia (TD) are associated with accelerated biological aging, immunological dysfunction, and premature morbidity and mortality. Older individuals are particularly vulnerable to TD development. As a characteristic of immunosenescence, alterations in the relative proportions of naïve or memory T cell subpopulations may be negatively or positively associated with brain structure abnormalities; however, whether these changes are correlated with TD remains unclear. In this study, we investigated correlations between distributions of T cell phenotypes and brain structure abnormalities (especially white matter) in schizophrenia patients with (TD) and without (NTD) TD (n = 50 and 58, respectively) relative to healthy controls (HC, n = 41). Immune markers, including naïve (CD45RA+), memory (CD45RO+), and apoptotic (CD95+) CD4+ and CD8+ T cells, were examined by flow cytometry, as were the intracellular levels of cytokines (interferon (IFN)-γ, interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α) in CD8 + CD45RA + CD95+ and CD8 + CD45RO + CD95+ T cells. MRI was employed to evaluate the fractional anisotropy (FA) of white matter tracts and subcortical volumes, following published routines. The percentage of CD8 + CD45RO + CD95+ T cells was higher in TD compared with NTD and HC groups and correlated with the choroid plexus volume in TD group. The intracellular level of IFN-γ in CD8 + CD45RO + CD95+ T cells, the FA of the fornix/stria terminalis, and the pallidum volume were correlated with orofacial TD, whereas the FAs of the inferior fronto-occipital fasciculus, cingulum, and superior longitudinal fasciculus were correlated with limb-truncal TD. These findings provide preliminary evidence that the association between immunosenescence-related T cell subpopulations and brain structure may underline the pathological process of TD.

Treatment of tardive dyskinesia with clonazepam: A case report.

Clonazepam has some evidence in the treatment of tardive dyskinesia. It can be used as an alternative treatment option in situations where vesicular monoamine transporter 2 inhibitors are not available or when it is not feasible to use them.

Severe Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Following the Initiation of Valbenazine for Tardive Dyskinesia: A Case Report.

Hyponatremia, a common electrolyte disorder, usually has a benign clinical course. However, patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) can suffer unfavorable outcomes, including mortality. Atypical antipsychotics, which are among the drugs associated with SIADH, also cause tardive dyskinesia, a condition that physicians can now effectively manage with the recently approved agent - valbenazine. We herein report a case of severe hyponatremia due to SIADH in a 58-year-old man who developed hyponatremia-induced generalized seizures six weeks after valbenazine was added to his regimen to mitigate olanzapine-associated tardive dyskinesia. His electrolyte derangement and clinical course improved following prompt recognition and treatment of SIADH. The temporal association between the commencement of valbenazine and the onset of SIADH suggests a possible but previously unreported link between valbenazine and the development of SIADH. Awareness of this uncommon association is relevant to patient safety.

Haloperidol-induced painless legs and moving toe syndrome in a schizophrenia patient: a case report.

Painless legs and moving toe syndrome (PoLMT) is a rare syndrome characterized by involuntary movements of the toe without pain. The exact etiology of the patient's PoLMT is unknown. We present a case of PoLMT in 45-year-old woman with a history of haloperidol intake for 10 months. Haloperidol was discontinued, and aripiprazole (15 mg) was initiated. After this switch, a reduction in movement was observed in the third and fourth toes; however, the second toe showed no discernible change.

Painless Legs and Moving Toe Syndrome (PoLMT) is a rare condition in which the toe moves on its own without any pain. No one knows for sure what causes PoLMT in patients. In this case report, we discuss a 45-year-old woman with PoLMT who was taking a drug called haloperidol for 10 months prior to their visit to hospital. Another drug, aripiprazole, was started after haloperidol was stopped. It was noticed that the third and fourth toes moved less after this switch in medication, but no change was noticed in the second toe.

Safety of Deutetrabenazine for the Treatment of Tardive Dyskinesia and Chorea Associated with Huntington Disease.

INTRODUCTION: Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor used to treat tardive dyskinesia (TD) and chorea associated with Huntington disease (HD). To enhance detection of safety signals across individual trials, integrated safety analyses of deutetrabenazine in TD and HD chorea were conducted. METHODS: For TD, safety data were integrated from two 12-week pivotal studies (ARM-TD and AIM-TD) and through week 15 of the open-label extension (OLE) study (RIM-TD). Data were analyzed by deutetrabenazine treatment group and placebo. For HD, safety data were integrated from the 12-week pivotal study (First-HD) and through week 15 of the OLE study (ARC-HD) for patients previously receiving placebo. Integrated deutetrabenazine data were compared with placebo from the pivotal study. RESULTS: For TD, deutetrabenazine (n = 384) was generally well tolerated compared with placebo (n = 130). Adverse event (AE) incidence was numerically higher in the response-driven deutetrabenazine vs the fixed-dose deutetrabenazine and placebo groups, respectively (any AE, 59.5% vs 44.4-50.0% and 53.8%; treatment-related AE, 38.1% vs 18.1-25.0% and 30.8%). Serious AEs were reported for 2.8-8.3% of patients in the deutetrabenazine groups and 6.9% in the placebo group. Common AEs (≥ 4%) included headache, somnolence, nausea, anxiety, fatigue, dry mouth, and diarrhea. AE incidence was higher during the titration vs maintenance periods. For HD, AE incidence was numerically higher with deutetrabenazine (n = 84) vs placebo (n = 45; any AE, 64.3% vs 60.0%; treatment-related AE, 38.1% vs 26.7%); serious AEs were reported for similar proportions for the deutetrabenazine and placebo groups, 2.4% and 2.2%, respectively. Common AEs (≥ 4%) included irritability, fall, depression, dry mouth, and fatigue. CONCLUSIONS: Data from an integrated analysis of studies in TD and an integrated analysis of studies of chorea in HD showed that deutetrabenazine has a favorable safety profile and is well tolerated across indications. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT02291861, NCT02195700, NCT01795859, NCT02198794, NCT01897896.

Unintended movements are often the first sign of Huntington disease. This type of unintended movement is called chorea in Huntington disease. Tardive dyskinesia causes unintended body movements. Deutetrabenazine is a medicine used to treat both types of movements. This report summarizes deutetrabenazine safety across five clinical studies. Safety was assessed via adverse events (side effects). Adverse events were compared between deutetrabenazine and inactive treatment (placebo). Serious adverse events were also compared. Serious adverse events cause substantial impairment or disruption. In tardive dyskinesia and chorea in Huntington disease studies, most patients kept taking deutetrabenazine. Adverse events were not a common reason to stop treatment. For tardive dyskinesia, adverse event rates were similar between deutetrabenazine (≤ 60%) and placebo (54%). Serious adverse event rates were also similar for deutetrabenazine (≤ 8%) and placebo (7%). Adverse events tended to be reported earlier in treatment. Common adverse events were headache, sleepiness, nausea, anxiety, fatigue, dry mouth, and diarrhea. For chorea in Huntington disease, adverse event rates were similar for deutetrabenazine (64%) and placebo (60%). Serious adverse event rates were also similar for deutetrabenazine (2%) and placebo (2%). Irritability, fall, depression, dry mouth, and fatigue were common adverse events. Adverse events were similar between deutetrabenazine and placebo in both conditions. Deutetrabenazine was well tolerated for patients with either tardive dyskinesia or chorea in Huntington disease.

Analysis of schizophrenia-associated genetic markers in the HLA region as risk factors for tardive dyskinesia.

OBJECTIVES: The pathology of Tardive Dyskinesia (TD) has yet to be fully understood, but there have been proposed hypotheses for the cause of this condition. Our team previously reported a possible association of TD with the Complement Component C4 gene in the HLA region. In this study, we explored the HLA region further by examining two previously identified schizophrenia-associated HLA-region single-nucleotide polymorphisms (SNPs), namely rs13194504 and rs210133. METHODS: The SNPs rs13194504 and rs210133 were tested for association with the occurrence and severity of TD in a sample of 172 schizophrenia patients who were recruited for four studies from three different clinical sites in Canada and USA. RESULTS: The rs13194504 AA genotype was associated with decreased severity for TD as measured by Abnormal Involuntary Movement Scale (AIMS) scores (p = 0.047) but not for TD occurrence. SNP rs210133 was not significantly associated with either TD occurrence or AIMS scores. CONCLUSION: Our findings suggest that the rs13194504 AA genotype may play a role in TD severity, while SNP rs210133 may not have a major role in the risk or severity of TD.

Clozapine Prescripers-Dogmatic or Pragmatic?

Clozapine, amongst antipsychotics, has a unique composite mode of action that might translate into an expanded therapeutic potential on clinical grounds. Sorely, clozapine remains underutilized.

Tardive Dyskinesia With Chorea-Ballism Improved by Valbenazine: A Case Report.

Tardive dyskinesia (TD) is an involuntary muscle movement typically caused by prolonged exposure to antipsychotic medications. Depending on the symptom severity and the affected body parts, it can cause a terrible decline in patients' daily activities and life quality. TD often persists despite discontinuation of the offending drugs. There was no approved or effective agent to treat the patients until valbenazine, a vesicular monoamine transporter-2 inhibitor, became available. We report the case of a 64-year-old woman who started to take antipsychotics at the age of her late 20s for her schizophrenic symptoms and later developed left arm chorea-ballism in mid-50s. The patient's involuntary movements got progressively worse even after being freed from the medications and caused severe body weight loss due to difficulties in taking meals. Daily treatment with valbenazine gradually mitigated her symptoms, resulting in significant improvement in her feeding activities, body weight, and daily life quality. This is the first report, to our knowledge, describing the therapeutic potential of valbenazine to improve chorea-ballism associated with TD. Our observation highlights that valbenazine may relieve a broader spectrum of antipsychotic-induced involuntary movements.

Comparative Analysis of Deutetrabenazine and Valbenazine as VMAT2 Inhibitors for Tardive Dyskinesia: A Systematic Review.

Background: Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine, have emerged as promising therapies for TD and several clinical trials have shown their efficacy. This study aims to compare the efficacy and safety profile of VMAT2 inhibitors, focusing on a recent trial conducted in the Asian population. Methods: We reviewed the PubMed, Cochrane Library, Embase database, and clinicaltrials.gov between January 2017 and October 2023, using the keywords "tardive dyskinesia" AND ("valbenazine" [all fields] OR " deutetrabenazine " [all fields]) AND "clinical trial". The reviewed articles were studied for efficacy and side effects. Results: An initial search yielded 230 articles, of which 104 were duplicates. Following the title and abstract screening, 25 additional articles were excluded. A full-text review resulted in the exclusion of 96 more articles. Ultimately, four double-blind clinical trials met the inclusion criteria. The deutetrabenazine studies demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared to placebo, with no difference in adverse events. The valbenazine studies showed favorable results in reducing TD symptoms and were well-tolerated. Discussion: The studies reviewed in this analysis underscore the potential of deutetrabenazine and valbenazine as valuable treatment options for TD in diverse populations. Both medications demonstrated significant improvements in AIMS scores, suggesting their effectiveness in managing TD symptoms. Additionally, they exhibited favorable safety profiles, with low rates of serious adverse events and no significant increase in QT prolongation, parkinsonism, suicidal ideation, or mortality. Conclusion: The studies reviewed highlight the promising efficacy and tolerability of deutetrabenazine and valbenazine as treatments for Tardive Dyskinesia, providing new hope for individuals affected by this challenging condition.

Bridging the gap between statistical significance and clinical relevance: A systematic review of minimum clinically important difference (MCID) thresholds of scales reported in movement disorders research.

Background: Minimum clinically important difference (MCID) is the smallest change in an outcome measure that is considered clinically meaningful. Using validated MCID thresholds for outcomes powers trials adequately to detect meaningful treatment effects, aids in their interpretation and guides development of new outcome measures. Objectives: To provide a comprehensive summary of MCID thresholds of various symptom severity scales reported in movement disorder. Methods: We conducted systematic review of the literature and included studies of one or more movement disorders, and reporting MCID scales. Results: 2763 reports were screened. Final review included 32 studies. Risk of bias (RoB) assessment showed most studies were of good quality. Most commonly evaluated scale was Unified Parkinson's Disease Rating Scale (UPDRS) (11 out of 32). Four studies assessing MDS-UPDRS had assessed its different sub-parts, reporting a change of 2.64,3.05,3.25 and 0.9 points to detect clinically meaningful improvement and 2.45,2.51,4.63 and 0.8 points to detect clinically meaningful worsening, for the Part I, II, III and IV, respectively. For Parts II + III, I + II + III and I + II + III + IV, MCID thresholds reported for clinically meaningful improvement were 5.73, 4.9, 6.7 and 7.1 points respectively; while those for clinically meaningful worsening were 4.7, 4.2, 5.2 and 6.3 points, respectively. MCID thresholds reported for other scales included Abnormal Involuntary Movement Scale (AIMS), Toronto Western Spasmodic Torticollis Rating Scale (TWSRS), and Burke-Fahn-Marsden Dystonia Scale (BFMD). Conclusion: This review summarizes all the MCID thresholds currently reported in Movement disorders research and provides a comprehensive resource for future trials, highlighting the need for standardized and validated MCID scales in movement disorder research.

Tardive dyskinesia in Asia- current clinical practice and the role of neurologists in the care pathway.

Tardive dyskinesia (TD) is a movement disorder that can arise as a side effect of treatment with dopamine receptor-blocking agents (DRBAs), including antipsychotic drugs (APDs) used to manage psychotic illnesses. Second-generation APDs (SGAs) are often preferred to first-generation drugs due to their lower propensity to cause TD, however many SGAs-treated patients still develop the condition. Although TD is a global health concern, evidence regarding the occurrence of TD and how it is managed in Asian countries is currently limited. This article reports the results of a systematic review of the published literature on TD focusing on its prevalence, types of patients, knowledge of the condition, causative factors, and usual treatment pathways in clinical practice in Asian countries. Epidemiological data suggest that the prevalence of TD is increasing globally due to an overall rise in APD use, contributing factors being polypharmacy with multiple APDs, the use of higher than necessary doses, and off-label use for non-psychotic indications. Although exact prevalence figures for TD in Asian countries are difficult to define, there is a similar pattern of rising APD use which will result in increasing numbers of TD patients in this region. These issues need to be addressed and strategies developed to minimize TD risk and manage this disabling condition which impacts patients' quality of life and daily functioning. To date, both research into TD has been predominantly psychiatry focused and the perspectives from neurologists regarding the clinical management of this challenging condition are scarce. However, neurologists have an essential role in managing the movement disorders manifestations that characterize TD. Optimum management of TD, therefore, should ideally involve collaboration between psychiatrists and neurologists in joint care pathways, wherever practical. Collaborative pathways are proposed in this article, and the challenges that will need to be addressed in Asian countries to improve the care of people with TD are highlighted, with a focus on the neurologist's viewpoint and the implications for the management of TD globally.

The Tardive Dyskinesia Impact Scale (TDIS), a novel patient-reported outcome measure in tardive dyskinesia: development and psychometric validation.

BACKGROUND: Tardive dyskinesia (TD), a movement disorder in which patients experience abnormal involuntary movements, can have profound negative impacts on physical, cognitive, and psychosocial functioning. The Abnormal Involuntary Movement Scale (AIMS), a clinician-rated outcome, is considered the gold standard for evaluating treatment efficacy in TD clinical trials. However, it provides little information about the impacts of uncontrolled movements from a patient perspective and can be cumbersome to administer in clinical settings. The Tardive Dyskinesia Impact Scale (TDIS) was developed as a patient-reported outcome measure to fulfill the need for a disease-specific impact assessment in TD. The objective of the present study was to develop and evaluate the psychometric properties of the TDIS to determine whether it is fit-for-purpose to measure TD impact. METHODS: Data from qualitative studies and phase 3 trials of a VMAT2 inhibitor for the treatment of TD (KINECT3 and KINECT4) were used to determine the psychometric properties of the TDIS. Qualitative research included concept elicitation and cognitive debriefing interviews with TD patients and their caregivers in order to assess how well the TDIS captured key domains of TD impact. Quantitative analyses to examine the psychometric properties of the TDIS included assessing construct validity (factor structure, known groups, and predictive validity) and responsiveness to change. RESULTS: Qualitative results showed that the TDIS captures the key TD impacts reported by patients and caregivers and that the TDIS was interpreted as intended and relevant to patients' experiences. Quantitative results found evidence of 2 underlying domains of the TDIS: physical and socioemotional (Comparative Fit Index > 0.9). Known groups and predictive validity indicated that, compared with the AIMS, the TDIS captures unique content (correlation between AIMS and TDIS = 0.2-0.28). The TDIS showed responsiveness to change in treatment, with TDIS scores improving over 48 weeks in the 2 phase 3 trials. CONCLUSIONS: The TDIS captures relevant information about the impact of TD and is easily administered in a clinician's office or patient's home. It may be used longitudinally to show changes in TD burden over time. The TDIS complements the AIMS; using these assessments together provides a more holistic assessment of TD.

Tardive dyskinesia is a condition where people have uncontrollable movements because of taking certain medications for a long time. It is still poorly understood how these uncontrollable movements affect a person's everyday activities. We created a questionnaire called the Tardive Dyskinesia Impact Scale (TDIS). The TDIS is a questionnaire where people with tardive dyskinesia rate how their symptoms affect daily activities such as speaking and walking. People can also rate how the uncontrollable movements make them feel. We used specific tests called psychometric tests to see if the TDIS measures the correct information and if the information is reliable. Findings from this study show that the TDIS is a good way to measure how a person's uncontrollable movements affect everyday activities. The results also show that when people take medicine to help with their symptoms, their TDIS scores are better. When patients stopped taking the medicine, their symptoms were worse, and their TDIS score was worse. The TDIS can help people explain how their uncontrollable movements affect their daily life. This can then help their doctors understand the person's condition better.