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2.
J Psychosoc Nurs Ment Health Serv ; 57(5): 11-14, 2019 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-31042295

RESUMEN

Tardive dyskinesia (TD), the choreoathetoid movements of fingers, arms, legs, and trunk and irregular stereotypical movements of the mouth, face, and tongue, has been the scourge of antipsychotic medications since the approval of chlorpromazine. TD tends to occur late in treatment and sometimes remains after discontinuation of the antipsychotic medication. With the recent approval of two medications, valbenazine (Ingrezza®) and deutetrabenazine (Austedo®), there are now treatments for this disfiguring consequence of dopamine-blocking medications. The current article distinguishes the movement disorder adverse effects of dopamine antagonists, explains the putative mechanism of action, and describes how best to treat TD with the new vesicular monamine transporter 2 (VMAT2) medications now approved by the U.S. Food and Drug Administration. [Journal of Psychosocial Nursing and Mental Health Services, 57(5), 11-14.].


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Discinesia Tardía/tratamiento farmacológico , Tetrabenazina/análogos & derivados , Valina/análogos & derivados , Antipsicóticos/uso terapéutico , Clorpromazina/uso terapéutico , Humanos , Enfermería Psiquiátrica , Tetrabenazina/farmacología , Tetrabenazina/uso terapéutico , Valina/farmacología , Valina/uso terapéutico
3.
Clin Neuropharmacol ; 42(2): 37-41, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30870235

RESUMEN

OBJECTIVES: The aim of this study was to review our "real-world" experience with the vesicular monoamine transporter 2 (VMAT2) inhibitors tetrabenazine (TBZ), deutetrabenazine (DTBZ), and valbenazine (VBZ) for treatment of hyperkinetic movement disorders. Access and adherence to VMAT2 inhibitors may be limited by insurance and regulatory issues, inexperience with their use by the prescribing physician, lack of efficacy, or side effects. METHODS: We performed a retrospective chart review, supplemented with a questionnaire, of all our patients treated with a VMAT2 inhibitor between January 1, 2017, and August 30, 2018. RESULTS: We identified 135 patients (57.8% male) and 178 prescriptions for VMAT2 inhibitors (TBZ, n = 45 [25.3%]; DTBZ, n = 104 [58.4%]; VBZ, n = 29 [16.3%]). Tourette syndrome/tics was the most common diagnosis (n = 67 [49.6%]) for which VMAT2 inhibitors were prescribed. The VMAT2 inhibitor mean treatment durations (range; SD) and daily dosages (range; SD) were as follows: TBZ (n = 31), 5.1 months (1-19; 3.9) at 48.8 mg (12.5-112.5; 29.6); DTBZ (n = 51), 8.0 months (0.25-16.5; 4.4) at 34.4 mg (6-96; 20.7); and VBZ (n = 20), 6.0 months (0.1-16; 5.6) at 64 mg (40-160; 35.3). The VMAT2 inhibitors effectively controlled hyperkinetic movement disorders as measured by a 1- to 4-point Likert scale (1 = normal or mildly ill, 4 = severely ill) comparing illness severity before starting and while on treatment (score of 1 in 13.0%-26.7% vs 60.9%-71.9% of patients). Side effects were mild and improved or resolved following dose reduction, drug cessation, or addition of adjunctive medications. CONCLUSIONS: The VMAT2 inhibitors are effective and safe in a range of hyperkinetic movement disorders but are not readily accessible by patients in the United States for indications not approved by the Food and Drug Administration.


Asunto(s)
Tetrabenazina/análogos & derivados , Tetrabenazina/uso terapéutico , Tics/tratamiento farmacológico , Síndrome de Tourette/tratamiento farmacológico , Valina/análogos & derivados , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tetrabenazina/farmacología , Tics/diagnóstico , Síndrome de Tourette/diagnóstico , Valina/farmacología , Valina/uso terapéutico , Adulto Joven
4.
J Pharm Pract ; 32(4): 450-457, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29455579

RESUMEN

Tardive dyskinesia is a potentially irreversible, debilitating, hyperkinetic movement disorder that can result from dopamine receptor antagonists. Prompt recognition and resolution of symptoms are instrumental in preventing disease irreversibility, though current treatment options have fallen short of robust, effective, and long-term symptom control. In April 2017, the Food and Drug Administration (FDA) approved 2 new vesicular monoamine transporter 2 (VMAT2) inhibitors, deutetrabenazine and valbenazine, for chorea related to Huntington's disease and tardive dyskinesia, respectively. These agents were pharmacologically modified from tetrabenazine, a VMAT2 inhibitor used off-label in the treatment of tardive dyskinesia. Despite FDA-labeled indications of deutetrabenazine and valbenazine, each agent was explored as a treatment option for those with tardive dyskinesia. In this study, the pharmacologic modifications of the 2 new VMAT2 inhibitors are described, with detailed explanation as to how these may impact clinical practice. The associated case series, observational studies, and clinical trials exploring their use in the treatment of tardive dyskinesia are reported with expert opinion on practice implication.


Asunto(s)
Discinesia Tardía/tratamiento farmacológico , Tetrabenazina/análogos & derivados , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Inhibidores de Captación Adrenérgica/administración & dosificación , Inhibidores de Captación Adrenérgica/farmacología , Antagonistas de Dopamina/efectos adversos , Etiquetado de Medicamentos , Humanos , Discinesia Tardía/fisiopatología , Tetrabenazina/administración & dosificación , Tetrabenazina/farmacología , Valina/administración & dosificación , Valina/análogos & derivados , Valina/farmacología , Proteínas de Transporte Vesicular de Monoaminas/metabolismo
6.
Asian J Psychiatr ; 36: 64-65, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29966890

RESUMEN

An 81 years old Jewish-Iranian lady, with a psychiatric history of postpartum depression in her twenties and a previous hospitalization due to a depressive episode accompanied by suicidal thoughts and a history of hearing loss and COPD, was hospitalized in the psychogeriatric department of our Mental Health Center due to repetitive incoherent sounds she was uttering for the past month, which increased in intensity and caused suicidal thoughts.


Asunto(s)
Agitación Psicomotora/fisiopatología , Tics/fisiopatología , Inhibidores de Captación Adrenérgica/farmacología , Anciano de 80 o más Años , Femenino , Humanos , Agitación Psicomotora/tratamiento farmacológico , Tetrabenazina/farmacología , Tics/tratamiento farmacológico
7.
Pharmacol Biochem Behav ; 172: 9-16, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30017858

RESUMEN

A single administration with morphine (30 mg/kg, i.p.) induced long-lasting hyperlocomotion in male ICR mice. Pretreatment of mice with a benzoquinolizine derivative tetrabenazine (TBZ; a reversible vesicular monoamine transporter-2 inhibitor) (1 mg/kg, i.p.) for 30 min significantly attenuated the hyperlocomotion induced by morphine, as compared with vehicle (saline)-pretreated mice. No significant change in locomotion was observed in mice pretreated with TBZ (1 mg/kg) alone. Mice treated with TBZ (1 mg/kg) showed an increase in immobility time in a tail suspension test, as compared with saline-treated mice. Pretreatment with TBZ (1 mg/kg) had no effect on morphine (1-30 mg/kg)-induced antinociception. TBZ at a dose of 1 mg/kg inhibited dopamine turnover (the ratio of 3,4-dihydroxyphenylacetic acid/dopamine) and 5-hydroxytryptamine turnover (the ratio of 5-hydroxyindoleacetic acid/5-hydroxytryptamine) in the cerebral cortex of mice challenged with morphine, as compared with saline-pretreated mice challenged with morphine. No stereotypic behavior was observed in mice treated with morphine (30 mg/kg) in combination with TBZ (1 mg/kg), so the reduction in observed locomotion did not result from induction of stereotypical behavior. Moreover, TBZ (1 and 2 mg/kg) pretreatment had no effect on stereotyped behaviors observed in mice challenged with 10 mg/kg methamphetamine. These data support the potential antagonistic actions of TBZ on some opiate actions, and encourage further exploration of potential effects on morphine reinforcement.


Asunto(s)
Inhibidores de Captación Adrenérgica/farmacología , Corteza Cerebral/efectos de los fármacos , Dopamina/metabolismo , Locomoción/efectos de los fármacos , Morfina/farmacología , Serotonina/metabolismo , Tetrabenazina/farmacología , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Animales , Corteza Cerebral/metabolismo , Masculino , Metanfetamina/farmacología , Ratones , Ratones Endogámicos ICR
8.
Expert Rev Neurother ; 18(8): 625-631, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29996061

RESUMEN

INTRODUCTION: Huntington's disease (HD) is an inherited neurodegenerative disorder for which no disease-modifying treatment is currently available. Only symptomatic treatment can be offered. Chorea is the most common motor manifestation of HD and may interfere with daily activities, reduce quality of life, and cause injury. Areas covered: Deutetrabenazine is the first deuterated drug and second drug after tetrabenazine, the classic vesicular monoamine transporter type 2 (VMAT2) inhibitor, to receive approval for the treatment of chorea associated with HD. This review, based largely on a detailed PubMed search, will summarize the pharmacological properties, clinical evidence of efficacy and tolerability of deutetrabenazine in the treatment of HD chorea. Expert commentary: Due to differences in pharmacology and pharmacokinetics, deutetrabenazine has shown promise that it is at least as effective as tetrabenazine in the treatment of HD chorea but has a lower risk of adverse effects. The role of VMAT2 inhibitors in the treatment of hyperkinetic movement disorders is expanding due to their efficacy and favorable tolerability profiles.


Asunto(s)
Inhibidores de Captación Adrenérgica/uso terapéutico , Enfermedad de Huntington/tratamiento farmacológico , Tetrabenazina/análogos & derivados , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Inhibidores de Captación Adrenérgica/efectos adversos , Inhibidores de Captación Adrenérgica/farmacocinética , Inhibidores de Captación Adrenérgica/farmacología , Humanos , Calidad de Vida , Tetrabenazina/efectos adversos , Tetrabenazina/farmacocinética , Tetrabenazina/farmacología , Tetrabenazina/uso terapéutico
9.
Neurology ; 91(3): e202-e207, 2018 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-29925548

RESUMEN

OBJECTIVE: To determine whether tetrabenazine (TBZ) use is associated with an increased incidence of depression and/or suicidal ideation. METHODS: In this retrospective cross-sectional study of the Enroll-HD database, we used multiple logistic regression analyses to determine whether TBZ use is associated with an increased incidence of depression and/or suicidal ideation. For both dependent variables (depression and suicidality), separate analyses were conducted on (1) all participants, (2) only participants with a history of depression, and (3) only participants with no history of depression. Adjustments were made for CAG repeat length, total motor score, total functional capacity, Symbol Digit Modalities Test score, sex, disease duration, history of depression (when applicable), antipsychotic use, and antidepressant use. RESULTS: Compared to participants who were not using TBZ (n = 3,548), TBZ users (n = 543) did not have an increased risk of depression (odds ratio [OR] = 0.78, p = 0.064). Participants taking TBZ actually had a relatively lower risk of suicidality (OR = 0.61, p = 0.043). Among only participants with a history of depression, those using TBZ had a lower incidence of depression (OR = 0.71, p = 0.016) and suicidal ideation (OR = 0.57, p = 0.028) compared to those not using TBZ. Finally, among only participants with no history of depression, TBZ use was not associated with a higher incidence of depression (OR = 1.59, p = 0.18) or suicidality (OR = 1.43, p = 0.66) compared to those who were not using TBZ. CONCLUSIONS: TBZ use was not associated with an increased incidence of depression or suicidality. These findings suggest that TBZ may be safe to use in patients with Huntington disease who have a history of depression.


Asunto(s)
Depresión/tratamiento farmacológico , Depresión/psicología , Enfermedad de Huntington/tratamiento farmacológico , Enfermedad de Huntington/psicología , Ideación Suicida , Tetrabenazina/uso terapéutico , Inhibidores de Captación Adrenérgica/farmacología , Inhibidores de Captación Adrenérgica/uso terapéutico , Adulto , Anciano , Depresión/epidemiología , Femenino , Humanos , Enfermedad de Huntington/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Tetrabenazina/farmacología , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores
10.
Drug Des Devel Ther ; 12: 1215-1238, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29795977

RESUMEN

Aim: The aim of this study was to summarize the characteristics, efficacy, and safety of vesicular monoamine transporter-2 (VMAT-2) inhibitors for treating tardive dyskinesia (TD). Materials and methods: We conducted a literature search in PubMed, Cochrane Database, and ClinicalTrials.gov, screening for systematic reviews, meta-analyses or double-blind, randomized, placebo-controlled trials (DBRPCTs) reporting efficacy or safety data of VMAT-2 inhibitors (tetrabenazine, deutetrabenazine, and valbenazine) in patients with TD. A random effects meta-analysis of efficacy and safety data from DBRPCTs was performed. Results: Two acute, 12-week DBRPCTs with deutetrabenazine 12-48 mg/day (n=413) and 4 acute, 4-6-week double-blind trials with valbenazine 12.5-100 mg/day (n=488) were meta-analyzable, without meta-analyzable, high-quality data for tetrabenazine. Regarding reduction in total Abnormal Involuntary Movement Scale (AIMS) scores (primary outcome), both deutetrabenazine (k=2, n=413, standardized mean difference [SMD] =-0.40, 95% confidence interval [CI] =-0.19, -0.62, p<0.001; weighted mean difference (WMD) =-1.44, 95% CI =-0.67, -2.19, p<0.001) and valbenazine (k=4, n=421, SMD =-0.58, 95% CI =-0.26, -0.91, p<0.001; WMD =-2.07, 95% CI =-1.08, -3.05, p<0.001) significantly outperformed placebo. Results were confirmed regarding responder rates (≥50% AIMS total score reduction; deutetrabenazine: risk ratio [RR] =2.13, 95% CI =1.10, 4.12, p=0.024, number-needed-to-treat [NNT] =7, 95% CI =3, 333, p=0.046; valbenazine: RR =3.05, 95% CI =1.81, 5.11, p<0.001, NNT =4, 95% CI =3, 6, p<0.001). Less consistent results emerged from patient-rated global impression-based response (p=0.15) and clinical global impression for deutetrabenazine (p=0.088), and for clinical global impression change for valbenazine (p=0.67). In an open-label extension (OLE) study of deutetrabenazine (≤54 weeks) and a dose-blinded valbenazine study (≤48 weeks), responder rates increased over time. With valbenazine, discontinuation effects were studied, showing TD symptom recurrence towards baseline severity levels within 4 weeks after valbenazine withdrawal. No increased cumulative or specific adverse (AEs) events versus placebo (acute trials) in extension versus acute trial data were observed. Conclusion: The 2 VMAT-2 inhibitors, valbenazine and deutetrabenazine, are effective in treating TD, both acutely and long-term, without concerns about increased risk of depression or suicide in the TD population. No head-to-head comparison among VMAT-2 inhibitors and no high-quality, meta-analyzable data are available for tetrabenazine in patients with TD.


Asunto(s)
Antipsicóticos/farmacología , Discinesia Tardía/tratamiento farmacológico , Tetrabenazina/análogos & derivados , Tetrabenazina/farmacología , Valina/análogos & derivados , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Valina/farmacología , Proteínas de Transporte Vesicular de Monoaminas/metabolismo
11.
Prog Med Chem ; 57(1): 87-111, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29680151

RESUMEN

The dopaminergic system plays a key role in the central nervous system, regulating executive function, arousal, reward, and motor control. Dysregulation of this critical monoaminergic system has been associated with diseases of the central nervous system including schizophrenia, Parkinson's disease, and disorders such as attention deficit hyperactivity disorders and addiction. Drugs that modify the dopaminergic system by modulating the activity of dopamine have been successful in demonstrating clinical efficacy by providing treatments for these diseases. Specifically, antipsychotics, both typical and atypical, while acting on a number of monoaminergic systems in the brain, primarily target the dopamine system via inhibition of postsynaptic dopamine receptors. The vesicular monoamine transporter 2 (VMAT2) is an integral presynaptic protein that regulates the packaging and subsequent release of dopamine and other monoamines from neuronal vesicles into the synapse. Despite acting on opposing sides of the synapse, both antipsychotics and VMAT2 inhibitors act to decrease the activity of central dopaminergic systems. Tardive dyskinesia is a disorder characterized by involuntary repetitive movements and thought to be a result of a hyperdopaminergic state precipitated by the use of antipsychotics. Valbenazine (NBI-98854), a novel compound that selectively inhibits VMAT2 through an active metabolite, has been developed for the treatment of tardive dyskinesia and is the first drug approved for the treatment of this disorder. This chapter describes the process leading to the discovery of valbenazine, its pharmacological characteristics, along with preclinical and clinical evidence of its efficacy.


Asunto(s)
Descubrimiento de Drogas , Tetrabenazina/análogos & derivados , Valina/análogos & derivados , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Animales , Humanos , Estructura Molecular , Relación Estructura-Actividad , Tetrabenazina/química , Tetrabenazina/farmacología , Valina/química , Valina/farmacología
12.
Consult Pharm ; 33(4): 201-209, 2018 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-29609698

RESUMEN

OBJECTIVE: To provide a review of tardive dyskinesia (TD) symptoms, etiology, pathophysiology, and treatments. DATA SOURCES: PubMed, Web of Science, ClinicalTrials. gov, and Google Scholar were searched for relevant literature using a combination of the following terms: tardive dyskinesia, treatment, management, guidelines, tetrabenazine, deutetrabenazine, and valbenazine. Sources were limited to human data. STUDY SELECTION/DATA EXTRACTION: Articles were reviewed for relevance to TD therapy. Reference lists were manually searched for other relevant articles. Selected literature was published between 1968 and 2017. DATA SYNTHESIS: This article reviews treatment options available for patients with TD. Many agents have been tried off-label to manage symptoms, with limited evidence of benefit. The Food and Drug Administration approved the first drug to treat TD valbenazine on April 11, 2017. CONCLUSION: TD is largely iatrogenic. Valbenazine's approval by the Food and Drug Administration was followed by the approval of deutetrabenazine, a drug with similar mechanism of action. Further data from postmarketing studies will be needed to verify that valbenazine's adverse effect profile is different from the profiles of tetrabenazine and deutetrabenazine.


Asunto(s)
Aprobación de Drogas , Discinesia Tardía/tratamiento farmacológico , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Humanos , Guías de Práctica Clínica como Asunto , Discinesia Tardía/fisiopatología , Tetrabenazina/efectos adversos , Tetrabenazina/análogos & derivados , Tetrabenazina/farmacología , Tetrabenazina/uso terapéutico , Estados Unidos , United States Food and Drug Administration , Valina/efectos adversos , Valina/análogos & derivados , Valina/farmacología , Valina/uso terapéutico
13.
Expert Rev Neurother ; 18(4): 323-332, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29557243

RESUMEN

INTRODUCTION: Tardive dyskinesia (TD) is an iatrogenic movement disorder caused by exposure to dopamine receptor blocking agents. Two vesicular monoamine transporter type 2 (VMAT2) inhibitors for the treatment of TD were approved by the US Food and Drug Administration in 2017: valbenazine and deutetrabenazine. Areas covered: A brief review of TD and its identification, as well as a review of older treatment interventions is provided, followed by a detailed synthesis regarding the clinical utility of valbenazine and deutetrabenazine. Expert commentary: As evidenced from well-designed clinical trials, both valbenazine and deutetrabenazine are efficacious and tolerable. They differ in terms of labeled instructions for frequency of administration (twice daily for deutetrabenazine vs. once daily for valbenazine), titration requirements (dose to efficacy/tolerability for deutetrabenazine vs. titrate to target dose of 80 mg/day for valbenazine), need for food (administer deutetrabenazine with food), drug-drug interactions (consider CYP2D6 modulators for deutetrabenazine vs. both CYP2D6 and CYP3A4 for valbenazine), contraindications (hepatic impairment for deutetrabenazine), and minor differences in adverse event profile.


Asunto(s)
Inhibidores de Captación Adrenérgica/farmacología , Antagonistas de Dopamina/efectos adversos , Discinesia Tardía/tratamiento farmacológico , Tetrabenazina/análogos & derivados , Valina/análogos & derivados , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Humanos , Discinesia Tardía/inducido químicamente , Tetrabenazina/farmacología , Valina/farmacología
14.
Neuropharmacology ; 138: 349-359, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29408363

RESUMEN

The mesolimbic dopamine (DA) system plays a critical role in behavioral activation and effort-based decision-making. DA depletion produces anergia (shifts to low effort options) in animals tested on effort-based decision-making tasks. Caffeine, the most consumed stimulant in the world, acts as an adenosine A1/A2A receptor antagonist, and in striatal areas DA D1 and D2 receptors are co-localized with adenosine A1 and A2A receptors respectively. In the present work, we evaluated the effect of caffeine on anergia induced by the VMAT-2 inhibitor tetrabenazine (TBZ), which depletes DA. Anergia was evaluated in a three-chamber T-maze task in which animals can chose between running on a wheel (RW) vs. sedentary activities such as consuming sucrose or sniffing a neutral odor. TBZ-caffeine interactions in ventral striatum were evaluated using DARPP-32 phosphorylation patterns as an intracellular marker of DA-adenosine receptor interaction. In the T-maze, control mice spent more time running and much less consuming sucrose or sniffing. TBZ (4.0 mg/kg) reduced ventral striatal DA tissue levels as measured by HPLC, and also shifted preferences in the T-maze, reducing selection of the reinforcer that involved vigorous activity (RW), but increasing consumption of a reinforcer that required little effort (sucrose), at doses that had no effect on independent measures of appetite or locomotion in a RW. Caffeine at doses that had no effect on their own reversed the effects of TBZ on T-maze performance, and also suppressed TBZ-induced pDARPP-32(Thr34) expression as measured by western blot, suggesting a role for D2-A2A interactions. These results support the idea that DA depletion produces anergia, but does not affect the primary motivational effects of sucrose. Caffeine, possibly by acting on A2A receptors in ventral striatum, reversed the DA depletion effects. It is possible that caffeine, like selective adenosine A2A antagonists, could have some therapeutic benefit for treating effort-related symptoms.


Asunto(s)
Dopamina/metabolismo , Actividad Motora/fisiología , Antagonistas de Receptores Purinérgicos P1/farmacología , Receptores Purinérgicos P1/metabolismo , Inhibidores de Captación Adrenérgica/farmacología , Animales , Apetito/efectos de los fármacos , Apetito/fisiología , Toma de Decisiones/efectos de los fármacos , Toma de Decisiones/fisiología , Antagonistas de Dopamina/farmacología , Fosfoproteína 32 Regulada por Dopamina y AMPc/metabolismo , Relación Dosis-Respuesta a Droga , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Fosforilación/efectos de los fármacos , Receptores de Dopamina D2/metabolismo , Tetrabenazina/farmacología , Estriado Ventral/efectos de los fármacos , Estriado Ventral/metabolismo , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Proteínas de Transporte Vesicular de Monoaminas/metabolismo
15.
Clin Schizophr Relat Psychoses ; 11(4): 214-220, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29341821

RESUMEN

Tardive dyskinesia remains a significant, potentially stigmatizing or crippling adverse effect for any patient treated with an antipsychotic medication. While second- and third-generation antipsychotics have exhibited lower annual incidence rates for tardive dyskinesia than classic or first-generation agents, 3.9% versus 5.5%, the estimated incidence rate is only modestly lower. When coupled with the fact that second- and third-generation antipsychotic medications have come to be employed in treating a wider range of disorders (e.g., autism spectrum disorders, mood disorders, personality disorders, etc.), it is clear that the population of patients exposed to the risk of tardive dyskinesia has expanded. On April 3, 2017, the U.S. Food and Drug Administration (FDA) approved a deuterated version of tetrabenazine (Xenozine®) for the treatment of the involuntary choreic movements associated with Huntington's disease. More recent data, however, have indicated that deuterium tetrabenazine or deutetrabenazine (Austedo®) is effective in treating tardive dyskinesia. Moreover, like the other derivative of tetrabenazine, valbenazine (Ingrezza®), deutetrabenazine offers less frequent dosing and a better short-term adverse effect profile than that of tetrabenazine. Longer use in a broader range of patients, however, will be required to identify risks and benefits not found in short-term trials, as well as optimal use parameters for treatment of tardive dyskinesia.


Asunto(s)
Inhibidores de Captación Adrenérgica/farmacología , Discinesia Tardía/tratamiento farmacológico , Tetrabenazina/análogos & derivados , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Inhibidores de Captación Adrenérgica/administración & dosificación , Inhibidores de Captación Adrenérgica/efectos adversos , Humanos , Tetrabenazina/administración & dosificación , Tetrabenazina/efectos adversos , Tetrabenazina/farmacología
16.
Expert Rev Clin Pharmacol ; 11(3): 209-217, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29338466

RESUMEN

INTRODUCTION: Valbenazine is a selective VMAT2 inhibitor that the FDA approved in April 2017 for the specific treatment of tardive dyskinesia (TD), a movement disorder commonly caused by dopamine blocking agents. Valbenazine acts to decrease dopamine release, reducing excessive movement found in TD. Areas covered: This drug profile reviews the development of valbenazine and the clinical trials that led to its approval as the first treatment specific to TD. The literature search was performed with the PubMed online database. Expert commentary: Two clinical trials assessing the efficacy of valbenazine have shown the reduction of antipsychotic-induced involuntary movement. No life threatening adverse effects were found. Data from a 42-week extension study demonstrated sustained response.


Asunto(s)
Dopamina/metabolismo , Discinesia Tardía/tratamiento farmacológico , Tetrabenazina/análogos & derivados , Valina/análogos & derivados , Adulto , Animales , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Antipsicóticos/farmacología , Aprobación de Drogas , Humanos , Discinesia Tardía/inducido químicamente , Tetrabenazina/efectos adversos , Tetrabenazina/farmacología , Tetrabenazina/uso terapéutico , Valina/efectos adversos , Valina/farmacología , Valina/uso terapéutico , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores
18.
Expert Rev Neurother ; 17(12): 1135-1144, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28971695

RESUMEN

INTRODUCTION: Chronic intake of typical neuroleptics or centrally acting dopamine receptor blocking antiemetics may cause onset of tardive syndromes. Various types exist. One of them is tardive dyskinesia, characterised by often stigmatising, purposeless, rapid, repetitive, stereotypic, involuntary movements of face, limbs or trunk. Effective symptomatic drug treatment options beyond application of tetrabenazine are rare. Tetrabenazine is usually administered three times daily due to the short half life of this agent. Areas covered: This narrative review discusses the value of valbenazine for the treatment of tardive dyskinesia as a therapeutic alternative to tetrabenazine. Expert commentary: Valbenazine is a selective inhibitor of vesicular monoamine transporter 2, which is metabolized to (+)-alpha-dihydrotetrabenazine. Valbenazine and particularly its metabolite inhibit vesicular monoamine transporter 2 function. Once daily intake of valbenazine ameliorated the severity of tardive dyskinesia. The chiral purity of valbenazine circumvents generation of the (-)alpha and (+) and (-)beta dihydrotetrabenazine metabolites of tetrabenazine or deutetrabenazine. Valbenazine and its metabolite do not antagonize postsynaptic monoamine receptors in contrast to the tetrabenazine formulations. Therefore one may hypothesize that fewer and less severe motor and psychopathological side effects will occur during valbenazine long term application compared with tetrabenazine or deutretrabenazine.


Asunto(s)
Inhibidores de Captación Adrenérgica/farmacología , Discinesia Tardía/tratamiento farmacológico , Tetrabenazina/análogos & derivados , Valina/análogos & derivados , Inhibidores de Captación Adrenérgica/administración & dosificación , Humanos , Tetrabenazina/administración & dosificación , Tetrabenazina/farmacología , Valina/administración & dosificación , Valina/farmacología
19.
J Clin Psychiatry ; 78(8): 1136-1147, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29022654

RESUMEN

​​ Tardive dyskinesia (TD) is a disorder characterized by involuntary movements, typically of the orofacial muscles and also of the extremities and other muscle groups. The condition is associated with exposure to dopamine receptor blocking agents, including antipsychotics. Because the indications and off-label uses for these agents have expanded over the last 2 decades, a larger number of patients are receiving antipsychotic medications than in the past. While evidence suggests that patients being treated with second-generation antipsychotics have less risk for developing TD than those treated with first-generation antipsychotics, the decreased risk is not as great as was originally expected. In addition, patients with chronic psychiatric conditions often require long-term use of antipsychotics, putting them at risk for TD. This article addresses the prevalence, risk factors, and prevention of TD; assessment strategies including diagnostic criteria and rating scales; and evidence for TD treatments, including 2 newly approved medications: deutetrabenazine and valbenazine. ​​​.


Asunto(s)
Antipsicóticos , Efectos Adversos a Largo Plazo , Discinesia Tardía , Tetrabenazina/análogos & derivados , Valina/análogos & derivados , Antipsicóticos/efectos adversos , Antipsicóticos/clasificación , Humanos , Efectos Adversos a Largo Plazo/inducido químicamente , Efectos Adversos a Largo Plazo/diagnóstico , Efectos Adversos a Largo Plazo/epidemiología , Efectos Adversos a Largo Plazo/prevención & control , Administración del Tratamiento Farmacológico , Fármacos Neuromusculares/farmacología , Discinesia Tardía/inducido químicamente , Discinesia Tardía/diagnóstico , Discinesia Tardía/epidemiología , Discinesia Tardía/prevención & control , Tetrabenazina/farmacología , Valina/farmacología , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores
20.
J Nat Prod ; 80(10): 2839-2844, 2017 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-28905625

RESUMEN

Effort-related choice tasks are used for studying depressive motivational symptoms such as anergia/fatigue. These studies investigated the ability of the dietary supplement curcumin to reverse the low-effort bias induced by the monoamine storage blocker tetrabenazine. Tetrabenazine shifted effort-related choice in rats, decreasing high-effort lever pressing but increasing chow intake. The effects of tetrabenazine were reversed by oral ingestion of curcumin (80.0-160.0 mg/kg) and infusions of curcumin into the cerebral ventricles (2.0-8.0 µg). Curcumin attenuates the effort-related effects of tetrabenazine in this model via actions on the brain, suggesting that curcumin may be useful for treating human motivational symptoms.


Asunto(s)
Curcumina/farmacología , Tetrabenazina/farmacología , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Administración Oral , Animales , Conducta de Elección , Curcuma/química , Depresión , Conducta Alimentaria/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Estructura Molecular , Motivación , Ratas , Ratas Sprague-Dawley
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