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1.
Expert Rev Neurother ; 21(1): 9-20, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33174440

RESUMO

Introduction: Tardive dyskinesia (TD) is a hyperkinetic movement disorder that arises as a complication of exposure to dopamine receptor blocking agents. Vesicular monoamine transporter type 2 (VMAT2) inhibitors reduce dyskinesia by decreasing transport of monoamines, including dopamine, into presynaptic vesicles, leaving unpackaged dopamine to be metabolized by monoamine oxidase. Deutetrabenazine was adapted from an earlier VMAT2 inhibitor, tetrabenazine, by substituting three deuterium isotopes in place of three hydrogen isotopes at the site of metabolic degradation to improve upon the pharmacokinetics of the parent compound. Areas covered: The authors reviewed the pivotal trials examining the safety and efficacy of deutetrabenazine, as well as long-term data from an open-label extension. Also reviewed were posters and oral presentations, as well as information from the product label and the United States Food and Drug Administration. Expert opinion: Deutetrabenazine is effective at decreasing dyskinesia in TD, but drug selection and cost-effectiveness between existing VMAT2 inhibitors are evolving areas of study. Other areas of investigation include novel anti-dyskinetic agents and use of deep brain stimulation.


Assuntos
Discinesias , Discinesia Tardia , Humanos , Discinesia Tardia/tratamento farmacológico , Tetrabenazina/análogos & derivados , Tetrabenazina/uso terapêutico , Estados Unidos , Proteínas Vesiculares de Transporte de Monoamina
2.
Dement Geriatr Cogn Disord ; 35(3-4): 183-96, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23445555

RESUMO

AIM: We sought to identify markers of motor and nonmotor function in Parkinson's disease (PD) using advanced neuroimaging techniques in subjects with PD. METHODS: We enrolled 26 nondemented PD subjects and 12 control subjects. All subjects underwent [(18)F]fluorodeoxyglucose positron emission computed tomography (FDG-PET) and magnetic resonance imaging, and a complete neuropsychological battery. RESULTS: FDG-PET of subjects with PD revealed significant metabolic elevations in the bilateral posterior lentiform nucleus, posterior cingulate, and parahippocampus, and metabolic reductions in the bilateral temporoparietal association cortex and occipital lobe versus controls. PD subjects had significant reductions in executive/attention function, memory/verbal learning, and speed of thinking, and significantly increased depression, anxiety and apathy scores compared with controls. Motor dysfunction correlated with increased metabolism in the posterior lentiform nucleus, pons, and cerebellum, and decreased metabolism in the temporoparietal lobe. Cognitive dysfunction correlated with increased posterior cingulate metabolism and decreased temporoparietal lobe metabolism. Depressive symptoms correlated with increased amygdala metabolism; anxiety scores correlated with decreased caudate metabolism, and apathy scores correlated with increased metabolism in the anterior cingulate and orbitofrontal lobe and decreased metabolism in the temporoparietal association cortex. CONCLUSIONS: Our findings showed that motor, cognitive, and emotional dysfunction in PD are associated with distinct patterns of cerebral metabolic changes.


Assuntos
Glicemia/metabolismo , Encéfalo/metabolismo , Doença de Parkinson/metabolismo , Idoso , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Feminino , Fluordesoxiglucose F18 , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico , Doença de Parkinson/psicologia , Tomografia por Emissão de Pósitrons , Curva ROC
3.
Mov Disord ; 28(3): 327-33, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23283708

RESUMO

Impulse control disorders (ICDs) are potentially serious side effects of dopamine agonist therapy in Parkinson's disease (PD), but prospective data are lacking about their incidence, time course, and risk factors. This work was a 4-year, prospective cohort study of outpatients with PD and no previous ICDs (N = 164). All subjects treated with a dopamine agonist during the study were followed longitudinally for new-onset ICDs. Baseline characteristics were compared in groups with (ICD+) and without (ICD-) subsequent ICDs. Forty-six subjects were treated with a dopamine agonist, including 25 who were newly treated and 21 who received ongoing dopamine agonist therapy. Of these 46 subjects, 18 (39.1%) developed new-onset ICDs. The timing of ICD onset varied from 3.0 to 114.0 months (median, 23.0) after initiation of dopamine agonist therapy. Baseline demographic characteristics were similar in ICD+ and ICD- groups. At baseline, ICD+ subjects had a greater prevalence of motor complications (61.1% versus 25.0%; P = 0.01) than ICD- subjects, despite comparable total dopaminergic medication usage in both groups (median, 150.0 versus 150.0 levodopa equivalents; P = 0.61). Compared with ICD- subjects, ICD+ subjects had a greater baseline prevalence of caffeine use (100% versus 66.7%; P = 0.007) and higher lifetime prevalence of cigarette smoking (44.4% versus 14.3%; P = 0.04). Peak dopamine agonist doses were higher in ICD+ than ICD- subjects (median 300.0 versus 165.0 L-dopa equivalents; P = 0.03), but cumulative dopamine agonist exposure was similar in both groups. In summary, the timing of new-onset ICDs in PD is highly variable. Risk factors include cigarette smoking, caffeine use, motor complications, and higher peak dopamine agonist dosage.


Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/induzido quimicamente , Transtornos Disruptivos, de Controle do Impulso e da Conduta/epidemiologia , Agonistas de Dopamina/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Fatores de Risco
5.
Neurologist ; 18(3): 120-4, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22549349

RESUMO

BACKGROUND: Episodes of subacute worsening of motor function occur commonly in Parkinson disease (PD), but there has been surprisingly little research about the clinical characteristics of these exacerbations in the outpatient setting. METHODS: Retrospective study of an established cohort of 120 outpatients with PD. Primary outcome measures were the frequency, causes, and outcomes of motor exacerbations. Statistical analysis was performed to compare baseline characteristics of subjects with subsequent exacerbations versus without subsequent exacerbations. RESULTS: Over an 18-month period, 43 exacerbations occurred, affecting 30 of 120 subjects (25.0%). Infection was the single most frequent underlying cause, accounting for 11 of 43 (25.6%) exacerbations. Other common etiologies were anxiety (n=8), medication errors (n=6), poor adherence (n=6), medication side effects (n=3), and postoperative decline (n=3). Overall, 35 episodes (81.4%) were attributable to reversible or treatable causes. Most subjects recovered fully, but 10 (33.3%) experienced recurrent episodes, 5 (16.7%) suffered permanent decline, and 1 died. At baseline, subjects with exacerbations had a significantly longer median disease duration (7.8 vs. 5.7 y, P=0.003), lower Mini-Mental State Examination scores (27.0±3.3 vs. 28.6±1.6, P=0.02), higher modified Hoehn and Yahr scores (2.2±0.5 vs. 1.9±0.5, P=0.006), greater dopaminergic medication use (median, 750.0 vs. 395.0 levodopa equivalents; P=0.009), and a greater prevalence of motor complications (55.2% vs. 29.4%, P=0.01) than subjects without exacerbations. CONCLUSIONS: Exacerbations are common in PD, associated with more advanced disease, and usually attributable to treatable secondary causes such as intercurrent infection. Increased recognition of these underlying causes may help to decrease morbidity, reduce health care costs, and optimize quality of care in PD.


Assuntos
Movimento/fisiologia , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/uso terapêutico , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Movimento/efeitos dos fármacos , Avaliação de Resultados em Cuidados de Saúde , Pacientes Ambulatoriais , Doença de Parkinson/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença
6.
Parkinsonism Relat Disord ; 17(2): 95-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21112806

RESUMO

BACKGROUND: Patient telephone calls are a major form of unreimbursed healthcare utilization in Parkinson's disease (PD), yet little is known about potential risk factors for frequent calling behavior. METHODS: Prospective cohort study of 175 non-demented outpatients with PD. Our primary outcome measure was the frequency of patient telephone calls over a three-month period relative to baseline demographics, State-Trait Anxiety Index (STAI) and Beck Anxiety Inventory (BAI) scores, Unified Parkinson's Disease Rating Scale (UPDRS) motor scores, and medication use. Based on the median call rate (1 call/3 months), subjects were dichotomized into frequent (≥2 calls) and infrequent (≤1 call) caller groups. RESULTS: A total of 297 calls were received, of which 264 (89%) were from the frequent caller group (n = 63 subjects), and only 33 (11%) were from the infrequent caller group (n = 112 subjects). Compared with calls from infrequent callers, those from frequent callers more commonly related to somatic symptoms of PD (46.8% vs. 19.4%, p = 0.007). In multivariate logistic regression analysis, independent predictors of frequent calling were: anxiety (STAI ≥55; adjusted OR = 2.62, p = 0.02), sleep disorders (adjusted OR = 2.36, p = 0.02), dyskinesias (adjusted OR = 3.07, p = 0.03), and dopamine agonist use (adjusted OR = 2.27, p = 0.03). Baseline demographics, UPDRS motor scores, and levodopa use were similar in both groups. CONCLUSIONS: Frequent patient telephone calls in PD are independently associated with anxiety, sleep disorders, dyskinesias, and dopamine agonist use, with a minority of patients accounting for the majority of calls. Aggressive treatment of these non-motor symptoms and motor complications might potentially reduce the burden of patient telephone calls in PD.


Assuntos
Linhas Diretas/estatística & dados numéricos , Doença de Parkinson/psicologia , Doença de Parkinson/terapia , Idoso , Ansiedade/etiologia , Ansiedade/psicologia , Ansiedade/terapia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Valor Preditivo dos Testes , Estudos Prospectivos , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/psicologia , Transtornos do Sono-Vigília/terapia , Fatores de Tempo
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