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BACKGROUND: There is little information on using clozapine in elderly patients with mental disorders from India. AIM: To evaluate the sociodemographic and clinical profile of elderly (age ≥ 60 years) patients started on clozapine. METHODOLOGY: The clozapine registry in the department was screened to identify elderly patients who were started on clozapine. Treatment records of these patients were reviewed to extract sociodemographic and clinical details. RESULTS: Out of the available information of 1058 patients in the registry, 42 (3.96â¯%) were elderly (≥ 60 years) patients. About two-thirds of the patients had treatment resistance, i.e., their psychotic illness had not responded to two adequate trials of antipsychotics, and the second most common indication for starting clozapine was tardive dystonia or tardive dyskinesia (23.8â¯%). The mean dose of clozapine was 135.89 (SD: 109.6; Range: 37.5-500; median: 87.5) mg/day. The mean duration of clozapine use at the time of data extraction for the study sample was 3.55 (SD: 2.15; Range 0.3-9; median: 3) years. At the last follow-up, about three-fourths of patients were experiencing at least one side effect, with constipation being the most common side effect, followed by sedation, weight gain, and hypersalivation. In only four patients, clozapine was stopped during the follow-up. In terms of effectiveness, majority of the patients were rated as much improved or very much improved on Clinical Global Impression-Improvement subscale. CONCLUSION: Clozapine can be safely used in elderly patients with mental disorders. Hence, clozapine should not be withheld in elderly patients with mental disorders whenever indicated.
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Antipsicóticos , Clozapina , Humanos , Clozapina/administración & dosificación , Clozapina/efectos adversos , Anciano , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , India , Trastornos Psicóticos/tratamiento farmacológico , Anciano de 80 o más Años , Sistema de Registros , Trastornos Mentales/tratamiento farmacológico , Discinesia Tardía/tratamiento farmacológicoAsunto(s)
Bruxismo , Trastornos de Deglución , Clorhidrato de Duloxetina , Discinesia Tardía , Humanos , Clorhidrato de Duloxetina/efectos adversos , Discinesia Tardía/inducido químicamente , Trastornos de Deglución/inducido químicamente , Bruxismo/inducido químicamente , Anciano de 80 o más Años , Femenino , Masculino , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversosRESUMEN
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.
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Preparaciones de Acción Retardada , Enfermedad de Huntington , Discinesia Tardía , Tetrabenazina , Humanos , Enfermedad de Huntington/tratamiento farmacológico , Enfermedad de Huntington/complicaciones , Discinesia Tardía/tratamiento farmacológico , Tetrabenazina/análogos & derivados , Tetrabenazina/uso terapéutico , Tetrabenazina/administración & dosificación , Tetrabenazina/farmacocinética , Tetrabenazina/efectos adversos , Corea/tratamiento farmacológico , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Inhibidores de Captación Adrenérgica/administración & dosificación , Inhibidores de Captación Adrenérgica/uso terapéutico , Inhibidores de Captación Adrenérgica/farmacocinética , Inhibidores de Captación Adrenérgica/efectos adversos , ComprimidosRESUMEN
BACKGROUND: Deep brain stimulation (DBS) has been reported as a therapy option for the motor dysfunction of severe tardive dystonia (TD). The major psychiatric diseases, however, are contraindications to DBS treatment in TD patients. METHODS: Six severe, medically refractory TD patients undergoing bilateral anterior capsulotomy combined with bilateral subthalamic nucleus (STN)-DBS treatment were studied retrospectively at two time points: pre-operation, and 1-3 years post-operation. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to assess the dystonia and disability. Depressive, anxiety, psychiatric symptoms, and Quality of Life (QoL) were evaluated using the 17-item Hamilton Depression Scale (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive and Negative Syndrome Scale (PANSS), and 36-item Short-Form Health Survey (SF-36), respectively. RESULTS: After receiving the combination treatment for 25 ± 11.6 months (range, 12-41 months), significant clinical symptom improvements were reported in TD patients. BFMDRS motor and disability scores were ameliorated by 78.5 ± 32.0% (p = 0.031) and 76.5 ± 38.6% (p = 0.031), respectively. The HAMD-17 and HAMA-14 scores were reduced by 60.3 ± 27.9% (p = 0.007) and 60.0 ± 24.6% (p = 0.009), respectively. Furthermore, the PANSS scores of the comorbidity schizophrenia TD patients decreased by 58.1 ± 6.0% (p = 0.022), and the QoL improved by 59.7 ± 14.1% (SF-36, p = 0.0001). During the research, there were no notable adverse effects or problems. CONCLUSION: Bilateral anterior capsulotomy combined with bilateral STN-DBS may be an effective and relatively safe treatment option for severe TD comorbid with major psychiatric disorders.
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Estimulación Encefálica Profunda , Núcleo Subtalámico , Discinesia Tardía , Humanos , Masculino , Estimulación Encefálica Profunda/efectos adversos , Persona de Mediana Edad , Núcleo Subtalámico/fisiología , Femenino , Discinesia Tardía/terapia , Adulto , Estudios Retrospectivos , Cápsula Interna , Terapia Combinada , Anciano , Calidad de VidaRESUMEN
BACKGROUND: Deutetrabenazine is approved for adults with tardive dyskinesia (TD). Data based on underlying psychiatric condition and baseline dopamine receptor antagonist (DRA) use are limited. METHODS: Patients with TD who completed parent studies ARM-TD or AIM-TD were eligible for the 3-year, open-label extension study (RIM-TD; NCT02198794). In RIM-TD, deutetrabenazine was titrated based on dyskinesia control and tolerability. In this post hoc analysis of RIM-TD, total motor Abnormal Involuntary Movement Scale (AIMS) score and adverse events (AEs) were analyzed by underlying condition and DRA use at parent study baseline. RESULTS: Of 343 patients enrolled in RIM-TD, 336 were included in the analysis by underlying condition, and 337 were included in the analysis by DRA use. One hundred eighty-nine of 205 (92%) patients with psychotic disorders (schizophrenia/schizoaffective disorder) and 65 of 131 (50%) with mood and other disorders (depression/bipolar disorder/other) were receiving a DRA. Mean (SE) deutetrabenazine doses at week 145 were 40.4 (1.13), 38.5 (1.21), 39.9 (1.00), and 38.5 (1.48) mg/d for patients with psychotic disorders, those with mood and other disorders, and those receiving DRAs or not, respectively. Mean (SD) changes in total motor AIMS score from this study baseline to week 145 were -6.3 (4.53), -7.1 (4.92), -6.1 (4.42), and -7.5 (5.19). Exposure-adjusted incidence rates (number of AEs/patient-years) of AEs were similar across groups: any (1.02, 1.71, 1.08, 1.97), serious (0.10, 0.12, 0.10, 0.12), and leading to discontinuation (0.07, 0.05, 0.06, 0.05). CONCLUSIONS: Long-term deutetrabenazine provided clinically meaningful improvements in TD-related movements, with a favorable benefit-risk profile, regardless of underlying condition or DRA use.
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Antagonistas de Dopamina , Discinesia Tardía , Tetrabenazina , Humanos , Discinesia Tardía/tratamiento farmacológico , Discinesia Tardía/inducido químicamente , Masculino , Femenino , Tetrabenazina/análogos & derivados , Tetrabenazina/farmacología , Tetrabenazina/efectos adversos , Tetrabenazina/administración & dosificación , Persona de Mediana Edad , Adulto , Antagonistas de Dopamina/efectos adversos , Antagonistas de Dopamina/administración & dosificación , Antagonistas de Dopamina/farmacología , Trastornos Psicóticos/tratamiento farmacológico , Anciano , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
PURPOSE: This study aimed to assess the association between antipsychotic doses and the risk of tardive dyskinesia (TD) in clinical practice using a Japanese claims database from 2010 to 2020. METHODS: The study population included patients 15 years or older with a diagnosis record of schizophrenia, depression, or bipolar disorder who were prescribed antipsychotics. Using a case-control design, we categorized patients newly diagnosed with TD as cases, with corresponding 1:10 matching in the control group. The primary endpoint was the relative risk of TD in the >median dose and ≤median dose groups, as determined using conditional logistic regression analysis adjusted for age. RESULTS: The analysis population included 58,452 patients, and the median daily antipsychotic dose was 75 mg/d of chlorpromazine equivalent (CPZE). Of these, 80 were identified as TD cases, and doses >75 mg/d were associated with a significantly increased risk of TD at the last prescription and the maximum dose, respectively, before the date of the first diagnosis of TD. Post-hoc analysis further showed a significant association between doses ≥300 mg/d and the risk of TD compared to doses ≤75 mg/d and doses >75 to <300 mg/d. Comparing ≥300 mg/d versus >75 to <300 mg/d, the odd ratios at the last prescription and maximum dose before the first diagnosis of TD were 3.40 and 3.50, respectively. CONCLUSIONS: In the Japanese medical claims database of patients receiving relatively low doses of antipsychotics, doses >75 mg/d were associated with an increased risk of TD in a dose-dependent manner.
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Antipsicóticos , Bases de Datos Factuales , Esquizofrenia , Discinesia Tardía , Humanos , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Femenino , Masculino , Estudios de Casos y Controles , Persona de Mediana Edad , Discinesia Tardía/inducido químicamente , Adulto , Japón/epidemiología , Esquizofrenia/tratamiento farmacológico , Anciano , Relación Dosis-Respuesta a Droga , Adulto Joven , Trastorno Bipolar/tratamiento farmacológico , AdolescenteRESUMEN
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.
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Citocinas , Inmunosenescencia , Esquizofrenia , Discinesia Tardía , Sustancia Blanca , Humanos , Esquizofrenia/patología , Esquizofrenia/inmunología , Esquizofrenia/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Sustancia Blanca/inmunología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Discinesia Tardía/patología , Discinesia Tardía/inmunología , Discinesia Tardía/diagnóstico por imagen , Citocinas/metabolismo , Fenotipo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Linfocitos T/inmunologíaRESUMEN
PURPOSE/BACKGROUND: Using data from KINECT® 4, a phase 3, 48-week study of valbenazine, post hoc analyses were conducted to assess long-term outcomes that are relevant to the real-world management of tardive dyskinesia (TD). METHODS/PROCEDURES: Post hoc analyses of the participants of the KINECT 4 study who completed 48 weeks of open-label valbenazine (40 or 80 mg) treatment were conducted. Valbenazine effects on TD were evaluated using the Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression of Change-TD (CGI-TD), and Patient Global Impression of Change (PGIC). FINDINGS/RESULTS: Of 103 participants completing 48 weeks of treatment, 55% experienced clinically meaningful improvement (defined as ≥2-point reduction in AIMS total score [sum of items 1 - 7, evaluated by site raters]) by week 4; at week 48, 97% met this threshold. The percentage of completers who achieved AIMS total score response thresholds of ≥10% to ≥90% increased over time, with 86% of completers reaching ≥50% improvement. Of the 40 (39%) completers with AIMS ≥50% response at week 8, 38 (95%) sustained this response at week 48; 81% of those who did not meet this threshold at week 8 had achieved it by week 48. At week 48, more than 85% of completers achieved CGI-TD and PGIC ratings of "much improved" or "very much improved." IMPLICATIONS/CONCLUSIONS: The majority of participants who completed 48 weeks of treatment with once-daily valbenazine experienced substantial clinically meaningful and sustained TD improvements. These findings indicate that valbenazine can be a highly effective long-term treatment in patients with TD.
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Discinesia Tardía , Tetrabenazina , Valina , Humanos , Tetrabenazina/análogos & derivados , Tetrabenazina/farmacología , Tetrabenazina/administración & dosificación , Tetrabenazina/efectos adversos , Discinesia Tardía/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Valina/análogos & derivados , Valina/administración & dosificación , Valina/farmacología , Valina/efectos adversos , Anciano , Resultado del Tratamiento , Adulto , Escala de Movimientos Involuntarios Anormales , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificaciónRESUMEN
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.
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Polimorfismo de Nucleótido Simple , Esquizofrenia , Discinesia Tardía , Humanos , Esquizofrenia/genética , Discinesia Tardía/genética , Femenino , Masculino , Adulto , Persona de Mediana Edad , Factores de Riesgo , Marcadores Genéticos , Índice de Severidad de la Enfermedad , Genotipo , Predisposición Genética a la Enfermedad , Canadá , Antipsicóticos/efectos adversosRESUMEN
BACKGROUND: Valbenazine is used for tardive movement disorders in adults. Current studies on its safety are mostly from clinical trials and small case reports, limiting information on rare adverse reactions. This study investigated valbenazine-related adverse event (AE) risk signals using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Valbenazine AEs data were collected from the FAERS database from 2017 Q2 to 2023 Q1, employing methods like reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean. RESULTS: After data cleaning and drug screening, there were 20,837 AEs primarily suspecting valbenazine, involving 26 system organ classes and 125 AEs related to valbenazine at the preferred terms level. AEs related to valbenazine were mainly concentrated in nervous system disorders, general disorders and administration site conditions, and psychiatric disorders. Eye disorders and gastrointestinal disorders are new AEs not labeled in the valbenazine instructions. In addition, some new potential AE signals were found, such as Tardive dyskinesia and eyelid function disorder. CONCLUSION: The common AEs of valbenazine in the real world are consistent with the instructions, but there are some newly discovered suspicious AEs.
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Sistemas de Registro de Reacción Adversa a Medicamentos , Tetrabenazina , United States Food and Drug Administration , Valina , Tetrabenazina/análogos & derivados , Tetrabenazina/efectos adversos , Humanos , Estados Unidos , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Valina/análogos & derivados , Valina/efectos adversos , Bases de Datos Factuales , Minería de Datos/métodos , Discinesia Tardía/inducido químicamente , Masculino , Teorema de Bayes , AdultoRESUMEN
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.
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Discinesia Tardía , Tetrabenazina , Valina , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Discinesia Tardía/tratamiento farmacológico , Discinesia Tardía/inducido químicamente , Tetrabenazina/efectos adversos , Tetrabenazina/análogos & derivados , Tetrabenazina/uso terapéutico , Valina/análogos & derivados , Proteínas de Transporte Vesicular de MonoaminasAsunto(s)
Amantadina , Recurrencia , Discinesia Tardía , Humanos , Discinesia Tardía/tratamiento farmacológico , Discinesia Tardía/inducido químicamente , Amantadina/uso terapéutico , Amantadina/efectos adversos , Masculino , Antiparkinsonianos/efectos adversos , Femenino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that "extrapyramidal symptoms" is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception that all DIMDs can be treated in the same way, potentially leading to the misuse and overprescribing of anticholinergics. DIMDs are neurobiologically and clinically distinct, with different treatment paradigms and varying levels of evidence for anticholinergic use. Whereas evidence indicates anticholinergics can be effective for DIP and dystonia, they are not recommended for TD, akathisia, or NMS; nor are they supported for preventing DIMDs except in individuals at high risk for acute dystonia. Anticholinergics may induce serious peripheral adverse effects (e.g., urinary retention) and central effects (e.g., impaired cognition), all of which can be highly concerning especially in older adults. Appropriate use of anticholinergics therefore requires careful consideration of the evidence for efficacy (e.g., supportive for DIP but not TD) and the risks for serious adverse events. If used, anticholinergic medications should be prescribed at the lowest effective dose and for limited periods of time. When discontinued, they should be tapered gradually.
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Antipsicóticos , Distonía , Trastornos Distónicos , Trastornos del Movimiento , Síndrome Neuroléptico Maligno , Discinesia Tardía , Humanos , Anciano , Distonía/inducido químicamente , Distonía/tratamiento farmacológico , Antagonistas Colinérgicos/efectos adversos , Agitación Psicomotora/tratamiento farmacológico , Trastornos del Movimiento/tratamiento farmacológico , Trastornos del Movimiento/etiología , Discinesia Tardía/inducido químicamente , Discinesia Tardía/tratamiento farmacológico , Antipsicóticos/efectos adversosRESUMEN
The differential diagnosis of chorea encompasses a broad range of disorders. In psychiatry, tardive dyskinesia may be difficult to discern from other causes, particularly when the family history is negative. A 59-year-old man with an unclear medical history had been using risperidone for over a decade when we first saw him. He presented with severe dyskinesia in all extremities. The family history for neuropsychiatric disorders was negative. We interpreted the movement disorder as tardive dyskinesia, but later he turned out to suffer from Huntington’s disease. To improve diagnostic accuracy, we should have more frequently re-evaluated the differential diagnosis and our family history should have been more thorough. We outline the diagnostic considerations in patients presenting with chorea. Finally, we highlight the value of diagnostic re-evaluation and thorough family history taking to optimize diagnostic accuracy in neuropsychiatry.
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Corea , Enfermedad de Huntington , Trastornos del Movimiento , Discinesia Tardía , Masculino , Humanos , Persona de Mediana Edad , Corea/diagnóstico , Corea/genética , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/genética , RisperidonaRESUMEN
PURPOSE: This post hoc analysis investigated whether a patient's underlying psychiatric disease (schizophrenia/schizoaffective disorder [SCHZ] or bipolar disorder/depressive disorder [MOOD]) influenced the efficacy or safety of valbenazine for tardive dyskinesia (TD) in an Asian population. METHODS: We analyzed data from J-KINECT, a multicenter, phase II/III, randomized, double-blind study, which consisted of a 6-week placebo-controlled period followed by a 42-week extension where Japanese patients with TD received once-daily 40- or 80-mg valbenazine. We compared the change from baseline in Abnormal Involuntary Movement Scale total score and Clinical Global Impression of TD score between patients with SCHZ and those with MOOD, and incidence of treatment-emergent adverse events. RESULTS: Of 256 patients included in the placebo-controlled period, 211 continued to the long-term extension. The mean change from baseline in Abnormal Involuntary Movement Scale total score at week 6 (95% confidence interval) was -1.8 (-3.2 to -0.5) and -3.3 (-4.7 to -1.9) in the valbenazine 40- and 80-mg groups, respectively (SCHZ group), and -2.4 (-3.9 to -0.9) and -3.5 (-5.1 to -1.9) in the valbenazine 40- and 80-mg groups, respectively (MOOD group), demonstrating improvement at either dose level over placebo, regardless of the underlying disease. These results were maintained to week 48, and improvements of Clinical Global Impression of TD scores were similar. There were no notable differences in the incidence of serious or fatal treatment-emergent adverse events by underlying disease; differences in the incidence of worsening schizophrenia and depression were attributed to underlying disease progression. CONCLUSIONS: Safety and efficacy of long-term valbenazine therapy for TD did not vary according to underlying psychiatric disease.
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Antipsicóticos , Trastorno Bipolar , Trastorno Depresivo , Trastornos Psicóticos , Esquizofrenia , Discinesia Tardía , Tetrabenazina , Valina , Humanos , Antipsicóticos/efectos adversos , Trastorno Bipolar/inducido químicamente , Trastorno Depresivo/tratamiento farmacológico , Japón , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/complicaciones , Discinesia Tardía/inducido químicamente , Tetrabenazina/análogos & derivados , Valina/análogos & derivadosAsunto(s)
Antipsicóticos , Quinolonas , Esquizofrenia , Discinesia Tardía , Tiofenos , Humanos , Antipsicóticos/efectos adversos , Quinolonas/efectos adversos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/complicaciones , Discinesia Tardía/inducido químicamente , Tiofenos/efectos adversos , Tiofenos/administración & dosificaciónAsunto(s)
Antipsicóticos , Clozapina , Polifarmacia , Discinesia Tardía , Humanos , Clozapina/efectos adversos , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Discinesia Tardía/inducido químicamente , Discinesia Tardía/tratamiento farmacológico , Masculino , Esquizofrenia/tratamiento farmacológico , Femenino , Resultado del Tratamiento , Persona de Mediana EdadRESUMEN
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.