RESUMO
Tardive dyskinesia (TD) is a movement disorder that appears after chronic use of drugs that block dopaminergic receptors such as antipsychotics. Besides the motor symptoms, patients with TD also present cognitive deficits. Neuroinflammatory mechanisms could be involved in the development of these symptoms. A previous study showed that cannabidiol (CBD), the major non-psychotomimetic compound of Cannabis sativa plant, prevents orofacial dyskinesia induced by typical antipsychotics by activating peroxisome proliferator-activated receptors gamma (PPARγ). Here, we investigated if CBD would also reverse haloperidol-induced orofacial dyskinesia and associated cognitive deficits. We also verified if these effects depend on PPARγ receptor activation. Daily treatment with haloperidol (3 mg/kg, 21 days) increased the frequency of vacuous chewing movements (VCM) and decreased the discrimination index in the novel object recognition test in male Swiss mice. CBD (60 mg/kg/daily) administered in the last 7 days of haloperidol treatment attenuated both behavioral effects. Furthermore, haloperidol increased IL-1ß and TNF-α levels in the striatum and hippocampus while CBD reverted these effects. The striatal and hippocampal levels of proinflammatory cytokines correlated with VCM frequency and discrimination index, respectively. Pretreatment with the PPARγ antagonist GW9662 (2 mg/kg/daily) blocked the behavioral effects of CBD. In conclusion, these results indicated that CBD could attenuate haloperidol-induced orofacial dyskinesia and improve non-motor symptoms associated with TD by activating PPARγ receptors.
Assuntos
Antipsicóticos/efeitos adversos , Canabidiol/farmacologia , Disfunção Cognitiva , Discinesias/tratamento farmacológico , PPAR gama/uso terapêutico , Discinesia Tardia/induzido quimicamente , Animais , Antidiscinéticos/efeitos adversos , Antidiscinéticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Canabidiol/administração & dosagem , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Corpo Estriado/efeitos dos fármacos , Haloperidol/efeitos adversos , Haloperidol/farmacologia , Masculino , Mastigação/efeitos dos fármacos , Camundongos , Neostriado/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
OBJECTIVE: To evaluate the long-term safety and efficacy of deutetrabenazine in patients with tardive dyskinesia (TD). METHOD: Patients with TD who completed the 12 week, phase 3, placebo-controlled trials were eligible to enter this open-label, single-arm study. The open-label study consisted of a 6 week dose-escalation phase and a long-term maintenance phase (clinic visits at Weeks 4, 6 and 15, and every 13 weeks until Week 106). Patients began deutetrabenazine at 12 mg/day, titrating up to a dose that was tolerable and provided adequate dyskinesia control, based on investigator judgement, with a maximum allowed dose of 48 mg/day (36 mg/day for patients taking strong cytochrome P450 2D6 (CYP2D6) inhibitors). Safety measures included incidence of adverse events (AEs) and scales used to monitor parkinsonism, akathisia/restlessness, anxiety, depression, suicidality and somnolence/sedation. Efficacy endpoints included the change in Abnormal Involuntary Movement Scale (AIMS) score (items 1 to 7) from baseline and the proportion of patients rated as 'Much Improved' or 'Very Much Improved' on the Clinical Global Impression of Change. RESULTS: A total of 343 patients enrolled in the extension study, and there were 331 patient-years of exposure in this analysis. The exposure-adjusted incidence rates of AEs with long-term treatment were comparable to or lower than those observed in the phase 3 trials. The mean (SE) change in AIMS score was -4.9 (0.4) at Week 54 (n = 146), - 6.3 (0.7) at Week 80 (n = 66) and -5.1 (2.0) at Week 106 (n = 8). CONCLUSIONS: Overall, long-term treatment with deutetrabenazine was efficacious, safe, and well tolerated in patients with TD. TRIAL REGISTRATION NUMBER: NCT02198794.
Assuntos
Antidiscinéticos/uso terapêutico , Discinesia Tardia/tratamento farmacológico , Tetrabenazina/análogos & derivados , Adulto , Idoso , Antidiscinéticos/efeitos adversos , Antipsicóticos/efeitos adversos , Inibidores do Citocromo P-450 CYP2D6/efeitos adversos , Inibidores do Citocromo P-450 CYP2D6/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/complicações , Transtornos do Humor/tratamento farmacológico , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico , Discinesia Tardia/fisiopatologia , Tetrabenazina/efeitos adversos , Tetrabenazina/uso terapêutico , Resultado do TratamentoAssuntos
Antidiscinéticos/farmacologia , Antidiscinéticos/uso terapêutico , Discinesia Induzida por Medicamentos/tratamento farmacológico , Transtornos Parkinsonianos/tratamento farmacológico , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Animais , Antidiscinéticos/efeitos adversos , Discinesia Induzida por Medicamentos/metabolismo , Humanos , Transtornos Parkinsonianos/metabolismo , Serotonina/metabolismo , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêuticoRESUMO
INTRODUCTION: Botulinum toxin (BoNT) is the first line therapy for cervical dystonia (CD), with most patients receiving many treatment sessions, and so come to recognize and expect the benefits and harms of BoNT, making it difficult to separate which adverse events (AEs) are driven by BoNT and which come from patients' expectations. METHODS: Using the results of three Cochrane systematic reviews of randomized controlled trials (RCTs) we pooled results to calculate the risk of general and specific AEs associated with BoNT, and the proportion of AEs that cannot be pharmacologically attributed to BoNT. RESULTS: Fifteen RCTs, enrolling 1604 patients, were included. BoNT was associated with an increased risk of AEs, but 79% of this increased risk cannot be pharmacologically attributed to BoNT. CONCLUSIONS: Patients with CD attach a considerable expectation of harm due to BoNT, reflected in the large proportion of non-pharmacologically-mediated AEs.
Assuntos
Toxinas Botulínicas Tipo A/efeitos adversos , Fármacos Neuromusculares/efeitos adversos , Torcicolo/tratamento farmacológico , Antidiscinéticos/efeitos adversos , Antidiscinéticos/uso terapêutico , Toxinas Botulínicas Tipo A/uso terapêutico , Transtornos de Deglutição/induzido quimicamente , Humanos , Debilidade Muscular/induzido quimicamente , Fármacos Neuromusculares/administração & dosagem , Efeito Placebo , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Torcicolo/diagnóstico , Resultado do TratamentoRESUMO
AIM: Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. MAIN METHODS: To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10µg, 10ng/kg ip) immediately after each administrations of haloperidol (0.625, 6.25, 12.5, and 25.0mg/kg ip), fluphenazine (0.5, 5.0mg/kg ip), clozapine (1.0, 10.0mg/kg ip), quetiapine (1.0, 10.0mg/kg ip), sulpiride (1.6, 16.0mg/kg ip), metoclopramide (2.5, 25.0mg/kg ip) or (1.0, 10.0mg/kg ip). Controls simultaneously received saline (5ml/kg ip). To assess the ECG presentation before and after neuroleptic/prokinetic medication, the assessment was at 1, 2, 3, 4, 5, 10, 15, 20 and 30min (first administration) as well as at 30min, 60min and 24h (first administration and subsequent administrations) and the ECG recording started prior to drug administration. KEY FINDINGS: Since very early, a prolonged QTc interval has been continually noted with haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats as a central common effect not seen with domperidone. Consistent counteraction appears with the stable gastric pentadecapeptide BPC 157. Thus, BPC 157 rapidly and permanently counteracts the QTc prolongation induced by neuroleptics and prokinetics. SIGNIFICANCE: Pentadecapeptide BPC 157 is suited for counteracting a prolonged QT interval.
Assuntos
Antidiscinéticos/efeitos adversos , Antipsicóticos/efeitos adversos , Antagonistas de Dopamina/efeitos adversos , Síndrome do QT Longo/prevenção & controle , Fragmentos de Peptídeos/uso terapêutico , Proteínas/uso terapêutico , Animais , Relação Dose-Resposta a Droga , Eletrocardiografia , Síndrome do QT Longo/induzido quimicamente , Masculino , Fragmentos de Peptídeos/administração & dosagem , Proteínas/administração & dosagem , Ratos Wistar , Fatores de TempoRESUMO
"Every child exhibiting dystonia merits an l-dopa trial, lest the potentially treatable condition of dopa-responsive dystonia (DRD) is missed" has been a commonly cited and highly conserved adage in movement disorders literature stemming from the 1980s. We here provide a historical perspective on this statement, discuss the current diagnostic and therapeutic applications of l-dopa in everyday neurologic practice, contrast these with its approved indications, and finish with our view on both a diagnostic and therapeutic trial in children and adults with dystonia. In light of the relatively low prevalence of DRDs, the large interindividual variation in the required l-dopa dose, the uncertainty about an adequate trial duration, the substantial advances in knowledge on etiology and pathophysiology of these disorders, and the availability of various state-of-the-art diagnostic tests, we think that a diagnostic l-dopa trial as a first step in the approach of early-onset dystonia (≤25 years) is outdated. Rather, in high-resource countries, we suggest to use l-dopa after biochemical corroboration of a defect in dopamine biosynthesis, in genetically confirmed DRD, or if nigrostriatal degeneration has been demonstrated by nuclear imaging in adult patients presenting with lower limb dystonia. Furthermore, our literature study on the effect of a therapeutic trial to gain symptomatic relief revealed that l-dopa has occasionally proven beneficial in several established "non-DRDs" and may therefore be considered in selected cases of dystonia due to other causes. In summary, we argue against the application of l-dopa in every patient with early-onset dystonia and support a more rational therapeutic use.
Assuntos
Antidiscinéticos/administração & dosagem , Distonia/diagnóstico , Distonia/tratamento farmacológico , Levodopa/administração & dosagem , Antidiscinéticos/efeitos adversos , Dopamina/biossíntese , Distonia/metabolismo , Humanos , Levodopa/efeitos adversosRESUMO
OBJECTIVES: To assess the frequency of impulse control disorders (ICDs) in patients with restless legs syndrome (RLS) with and without augmentation under dopaminergic therapy in a case-control study. Augmentation and ICDs are both serious complications of dopaminergic treatment of RLS but little is known about possible associations between these drug-induced disorders. METHODS: In total, 58 patients with idiopathic RLS diagnosed according to the International Restless Legs Syndrome Study Group criteria were recruited. Of these, 35 patients had augmentation. The frequency of ICD symptoms was assessed using semi-structural interviews. RESULTS: Demographic variables did not differ between patients with RLS with and without augmentation but those with augmentation took higher dopaminergic medication than patients without augmentation. Twenty-three patients with RLS (39.7%) had ICD symptoms, with 12 patients (20.7%) having definitive ICDs. Patients with augmentation had an increased risk of expressing ICD symptoms (p = 0.007, odds ratio 5.64, 95% confidence interval 1.59-20.02). CONCLUSIONS: Patients with RLS with augmentation have an almost 6-fold increased risk of exhibiting ICD symptoms. This implies that augmentation and ICDs are related and may share a common pathophysiology. Moreover, our results have clinical implications, suggesting that patients with RLS with augmentation should be screened for ICD symptoms.
Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/complicações , Dopaminérgicos/efeitos adversos , Dopaminérgicos/uso terapêutico , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/tratamento farmacológico , Antidiscinéticos/efeitos adversos , Antidiscinéticos/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Entrevista Psicológica , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Síndrome das Pernas Inquietas/psicologia , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Dyskinesias encompass a variety of different hyperkinetic phenomenologies, particularly chorea, dystonia, stereotypies, and akathisia. Levodopa-induced dyskinesia (LID) is one of the main types of drug-induced dyskinesia, occurring in patients with Parkinson's disease (PD) who have been treated with levodopa for long time, but this side effect may be encountered even within a few weeks or months after initiation of levodopa therapy. Based on the temporal pattern in relationship to levodopa dosing, LIDs are divided into "peak-dose dyskinesia," "diphasic dyskinesia," and "wearing off" or "off-period" dyskinesia, of which peak-dose dyskinesia is the most common, followed by off-period, and then diphasic dyskinesia. Treatment strategy includes identifying the kind of dyskinesia and tailoring treatment accordingly. Peak-dose dyskinesia is treated mainly by reducing individual doses of levodopa and adding amantadine and dopamine agonists, whereas off-period dystonia often responds to baclofen and botulinum toxin injections. Diphasic dyskinesias, occurring particularly in patients with young-onset PD, are the most difficult to treat. While fractionation of levodopa dosage is the most frequently utilized strategy, many patients require deep brain stimulation to control their troublesome motor fluctuations and LIDs. A variety of emerging (experimental) drugs currently in development promise to provide better control of LIDs and other levodopa-related complications in the near future.
Assuntos
Antidiscinéticos/efeitos adversos , Discinesia Induzida por Medicamentos/terapia , Levodopa/efeitos adversos , Amantadina/uso terapêutico , Antidiscinéticos/administração & dosagem , Agonistas de Dopamina/uso terapêutico , Humanos , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The aim of this study was to investigate the efficacy and side effects of botulinum toxin (BTX) in the treatment of hemifacial spasm (HFS). We also focused on the divergence between different injection techniques and commercial forms. We retrospectively evaluated 470 sessions of BTX injections administered to 68 patients with HFS. The initial time of improvement, duration and degree of improvement, and frequency and duration of adverse effects were analysed. Pretarsal and preseptal injections and Botox (Allergan, Irvine, CA, USA) and Dysport (Ipsen Biopharmaceuticals, Paris, France) brands were compared in terms of efficacy and side effects, accompanied by a review of papers which reported BTX treatment of HFS. An average of 34.5 units was used per patient. The first improvement was felt after 8 days and lasted for 14.8 weeks. Patients experienced a 73.7% improvement. In 79.7% of injections, no adverse effect was reported, in 4.9% erythema, ecchymosis, and swelling in the injection area, in 3.6% facial asymmetry, in 3.4% ptosis, in 3.2% diplopia, and in 2.3% difficulty of eye closure was detected. Patients reported 75% improvement on average after 314 sessions of pretarsal injections and 72.7% improvement after 156 sessions of preseptal injections (p=0.001). The efficacy and side effects of Botox and Dysport were similar. BTX is an effective and safe treatment option for HFS. No difference was determined between Botox and Dysport, and pretarsal injection is better than preseptal injection regarding the reported degree of improvement.
Assuntos
Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Espasmo Hemifacial/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidiscinéticos/administração & dosagem , Antidiscinéticos/efeitos adversos , Toxinas Botulínicas/administração & dosagem , Toxinas Botulínicas/efeitos adversos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Toxinas Botulínicas Tipo A/uso terapêutico , Química Farmacêutica , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This narrative review reports on the pharmacological and pharmacokinetic properties of rotigotine, a non-ergolinic D3/D2/D1 dopamine receptor agonist approved for the treatment of early- and advanced-stage Parkinson's disease (PD) and moderate to severe restless legs syndrome (RLS). Rotigotine is formulated as a transdermal patch providing continuous drug delivery over 24 h, with a plasma concentration profile similar to that of administration via continuous intravenous infusion. Absolute bioavailability after 24 h transdermal delivery is 37 % of the applied rotigotine dose. Following a single administration of rotigotine transdermal system (24-h patch-on period), most of the absorbed drug is eliminated in urine and feces as sulphated and glucuronidated conjugates within 24 h of patch removal. The drug shows a high apparent volume of distribution (>2500 L) and a total body clearance of 300-600 L/h. Rotigotine transdermal system provides dose-proportional pharmacokinetics up to supratherapeutic dose rates of 24 mg/24 h, with steady-state plasma drug concentrations attained within 1-2 days of daily dosing. The pharmacokinetics of rotigotine transdermal patch are similar in healthy subjects, patients with early- or advanced-stage PD, and patients with RLS when comparing dose-normalized area under the plasma concentration-time curve (AUC) and maximum plasma drug concentration (Cmax), as well as half-life and other pharmacokinetic parameters. Also, it is not influenced in a relevant manner by age, sex, ethnicity, advanced renal insufficiency, or moderate hepatic impairment. No clinically relevant drug-drug interactions were observed following co-administration of rotigotine with levodopa/carbidopa, domperidone, or the CYP450 inhibitors cimetidine or omeprazole. Also, pharmacodynamics and pharmacokinetics of an oral hormonal contraceptive were not influenced by rotigotine co-administration. Rotigotine was generally well tolerated, with an adverse event profile consistent with dopaminergic stimulation and use of a transdermal patch. These observations, combined with the long-term efficacy demonstrated in clinical studies, support the use of rotigotine as a continuous non-ergot D3/D2/D1 dopamine receptor agonist in the treatment of PD and RLS.
Assuntos
Antidiscinéticos/farmacocinética , Agonistas de Dopamina/farmacocinética , Medicina Baseada em Evidências , Doença de Parkinson/tratamento farmacológico , Síndrome das Pernas Inquietas/tratamento farmacológico , Tetra-Hidronaftalenos/farmacocinética , Tiofenos/farmacocinética , Adesivo Transdérmico , Animais , Antidiscinéticos/administração & dosagem , Antidiscinéticos/efeitos adversos , Antidiscinéticos/uso terapêutico , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/farmacocinética , Antiparkinsonianos/uso terapêutico , Comorbidade , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Interações Medicamentosas , Humanos , Doença de Parkinson/epidemiologia , Doença de Parkinson/metabolismo , Guias de Prática Clínica como Assunto , Síndrome das Pernas Inquietas/epidemiologia , Síndrome das Pernas Inquietas/metabolismo , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/efeitos adversos , Tetra-Hidronaftalenos/uso terapêutico , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Tiofenos/uso terapêutico , Adesivo Transdérmico/efeitos adversosRESUMO
BACKGROUND: Chronic anal fissure (CAF) is perpetuated by high sphincter pressures and secondary local ischemia. Pharmacological approaches include topical nitrates and botulinum toxin (BT), which both help to decrease the sphincter pressure. AIMS & OBJECTIVES: The aims of the present study were to assess the efficacy and safety of BT injection and combined treatment with BT injection and lowered dose glyceryltrinitrate (GTN) cream for the treatment of CAF. We hypothesised that combined treatment would have a synergistic effect on healing. METHODS: Forty-one consecutive patients with CAF were randomly assigned to receive one of the following treatments: Group A, injection of BT (20 U into internal anal sphincter) and Group B, BT injection (20 units) and subsequent thrice daily topical applications of half-dose 0.2% GTN cream for 6 weeks. Patients were followed up at 6 and 12 weeks and were assessed for healing of anal fissure, by means of visual inspection using fissure grades; for faecal incontinence, using Cleveland Clinic incontinence scores; and for fissure pain and headache using a numeric pain rating scale. RESULTS: Fissure healing was similar in the two groups at both 6 (30% in BT and GTN and 33% in BT only) and 12 weeks (50% in BT and GTN vs 57% in BT-only group). Neither the change in pain score from 6 to 12 weeks, nor the overall level of pain was significantly different in the 2 groups. Moderate or severe headaches were suffered by 58% of patients using GTN. CONCLUSION: Single-agent treatment by means of BT injection alone was well tolerated compared with combination treatment with BT injection and GTN cream, with no significant differences in healing of CAF observed in this small study.
Assuntos
Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Fissura Anal/tratamento farmacológico , Nitroglicerina/uso terapêutico , Vasodilatadores/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidiscinéticos/efeitos adversos , Toxinas Botulínicas/efeitos adversos , Doença Crônica , Quimioterapia Combinada , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Nitroglicerina/efeitos adversos , Medição da Dor , Resultado do Tratamento , Vasodilatadores/efeitos adversos , Cicatrização/efeitos dos fármacosRESUMO
Oral medication, botulinum toxin injections, and deep brain stimulation are the current mainstays of treatment for dystonia. In addition, physical and other supportive therapies may help prevent further complications (eg, contractures) and improve function. This review discusses evidence-based medical treatment of dystonia with an emphasis on recent advances in treatment. We will also review the current treatment approaches and suggest ways in which these therapies can be applied to individuals with dystonia.
Assuntos
Distonia/terapia , Antidiscinéticos/efeitos adversos , Antidiscinéticos/uso terapêutico , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/métodos , Distonia/tratamento farmacológico , Distonia/cirurgia , Humanos , Modalidades de Fisioterapia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The original material of monitoring of 118 patients with chronic anal fissure is presented in the article. Patients' mean age was 48.9+-10.5 years. It was used injections of medicine of botulinum toxin of type A (Lantox) by its introduction in internal anal sphincter in all patients. There was granulating wound with signs of marginal epithelialization in 59.3% of cases on the 10th day after injection. It was detected complete epithelialization of dermis defect in 93.2% of cases on the 21st day, after six weeks - in 100% of cases. According to anorectal profilometry the index of maximal and average pressure in the anal canal at the level of the internal sphincter in patients at rest decreased to norm. Lantox introduction leads to rapid and persistent reduction of pain intensity. "Lantox" use in ambulatory practice permits to minimize the indications for surgical treatment.
Assuntos
Toxinas Botulínicas Tipo A , Fissura Anal , Espasmo/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Adulto , Canal Anal/efeitos dos fármacos , Canal Anal/fisiopatologia , Antidiscinéticos/administração & dosagem , Antidiscinéticos/efeitos adversos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Vias de Administração de Medicamentos , Monitoramento de Medicamentos , Feminino , Fissura Anal/tratamento farmacológico , Fissura Anal/etiologia , Fissura Anal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Espasmo/complicações , Espasmo/fisiopatologia , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the efficacy and safety of 2 doses of botulinum toxin type B (rimabotulinumtoxinB, BoNT/B) in spastic upper limb muscles. DESIGN: Randomized, double-blind, placebo-controlled trial with a 3-month follow-up. SETTING: Tertiary care center. PARTICIPANTS: Referred sample of adult hemiparetic patients (N=24) with disabling elbow flexor overactivity after stroke or traumatic brain injury. INTERVENTIONS: Injection of 10,000U of rimabotulinumtoxinB (fixed 2500U dose into elbow flexors; n=8), 15,000U (5000U into elbow flexors; n=8), or placebo (n=8) into overactive upper limb muscles selected as per investigator's discretion. MAIN OUTCOME MEASURES: At 1 month postinjection, active range of elbow extension (goniometry; primary outcome); active upper limb function (Modified Frenchay Scale [MFS]); subjective global self-assessment (GSA) of arm pain, stiffness, and function; rapid alternating elbow flexion-extension movement frequency over the maximal range; elbow flexor spasticity grade and angle (Tardieu), and tone (Ashworth). RESULTS: No adverse effects were associated with either BoNT/B dose. Both doses improved active elbow extension versus placebo (+8.3°; 95% confidence interval, 1.1°-15.5°; analysis of covariance, P=.028). The high dose of BoNT/B also improved subject-perceived stiffness (P=.005) and the composite pain, stiffness, and function GSA (P=.017), effects that persisted 3 months from injection. No MFS change was demonstrated, although subjects with a baseline MFS <70/100 seemed more likely to benefit from BoNT/B. CONCLUSIONS: In this short-term study, BoNT/B up to 15,000U into spastic upper limb muscles, including the elbow flexors, was well tolerated and improved active elbow extension and subject-perceived stiffness.
Assuntos
Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Paralisia/tratamento farmacológico , Adulto , Idoso , Antidiscinéticos/administração & dosagem , Antidiscinéticos/efeitos adversos , Braço , Toxinas Botulínicas/administração & dosagem , Toxinas Botulínicas/efeitos adversos , Toxinas Botulínicas Tipo A , Avaliação da Deficiência , Método Duplo-Cego , Cotovelo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular , Amplitude de Movimento Articular , Centros de Atenção TerciáriaRESUMO
INTRODUCTION: Previously, controlled trials have demonstrated the efficacy and tolerability of fixed doses of incobotulinumtoxinA (Xeomin, NT 201, botulinum toxin type A free from complexing proteins) to treat cervical dystonia (CD). To explore the clinical relevance of these findings, this study evaluated long-term use of flexible dosing regimens of incobotulinumtoxinA in a setting close to real-life clinical practice. METHODS: Patients with CD received five injection sessions of incobotulinumtoxinA using flexible intervals (10-24 weeks) and dosing (≤300 Units) based on patients' needs. Outcome measures included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), the Dystonia Discomfort Scale (DDS), Investigator Global Assessment of Efficacy (IGAE) and Patient Evaluation of Global Response (PEGR). RESULTS: Of 76 patients enrolled (men: 34%; naïve to botulinum toxin: 25%), 64 completed the study, receiving treatment over a duration of 49.3-114.1 weeks (total maximum duration: 121 weeks). Mean TWSTRS-Total and DDS scores significantly improved from study baseline to 4 weeks after each injection session (ranges of improvement: TWSTRS-Total: -11.7 to -14.3; DDS: -20.2 to -23.0). Up to 81.6% of investigators rated the efficacy as 'good' or 'very good' (IGAE) and up to 78.9% of patients rated the treatment response as 'improved' (PEGR). The most common adverse events were dysphagia, nasopharyngitis and headache. CONCLUSIONS: In this long-term study, incobotulinumtoxinA was administered using more flexible dosing regimens than those permitted in previous controlled trials. Repeated injections of highly purified incobotulinumtoxinA are effective and well tolerated for the treatment of CD in a setting close to real-life clinical practice.
Assuntos
Antidiscinéticos/efeitos adversos , Antidiscinéticos/uso terapêutico , Toxinas Botulínicas Tipo A/efeitos adversos , Toxinas Botulínicas Tipo A/uso terapêutico , Torcicolo/tratamento farmacológico , Idoso , Antidiscinéticos/administração & dosagem , Toxinas Botulínicas Tipo A/administração & dosagem , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medição da Dor , Satisfação do Paciente , Estudos Prospectivos , Torcicolo/fisiopatologia , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: Botulinum toxin injection into the lower esophageal sphincter is an established therapy for the treatment of achalasia. This review will highlight recent studies that shed light on the role of Botulinum toxin injection in the management of achalasia. RECENT FINDINGS: Recent studies have shown that Botulinum toxin injection is the most common initial endoscopic therapy for achalasia, most likely due to its safety and ease of administration. However, this trend represents a deviation from recent guidelines which consider Botulinum toxin injection less efficacious than alternative treatments like pneumatic dilation and laparoscopic Heller myotomy. Over the past decade, multiple commercial formulations of Botulinum toxin injection have been introduced, but the techniques, indications, and therapeutic efficacy for Botulinum toxin have largely remained unchanged. This review will evaluate recent guidelines, consensus articles, meta-analyses, and landmark studies to expound on the short and long-term efficacy of Botulinum toxin, injection dosages, and technique, as well as its efficacy compared to pneumatic dilation, myotomy, and combination therapy. SUMMARY: Despite its relatively poor long-term efficacy, Botulinum toxin injection continues to play an important role in elderly patients with comorbidities and as salvage therapy for achalasia.
Assuntos
Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Acalasia Esofágica/tratamento farmacológico , Antidiscinéticos/administração & dosagem , Antidiscinéticos/efeitos adversos , Toxinas Botulínicas/administração & dosagem , Toxinas Botulínicas/efeitos adversos , Terapia Combinada , Dilatação , Relação Dose-Resposta a Droga , Acalasia Esofágica/terapia , Humanos , Injeções Intralesionais , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to review the effect of rimabotulinum toxin (BoNT-B) for focal hypertonicity management in children with cerebral palsy and secondary nonresponse to onabotulinum toxin treated at the authors' tertiary care academic medical center. DESIGN: A retrospective review of the medical treatment of children was conducted at the authors' institution (March 16, 2001, to August 2, 2002) using the key words botulinum toxin B and Myobloc (Solstice Neurosciences Inc, South San Francisco, CA). Demographic information was analyzed using descriptive statistics (number [percentage] and mean [range]). The Pearson χ test was used to evaluate differences in incidence of adverse events. RESULTS: Eighty-two children had BoNT-B injections (116 treatments). Overall, 26.8% (19/71) of the children or their parents/guardians reported no or minimal response to the injections, with 89.5% (17/19) of these children having secondary nonresponse to onabotulinum toxin. Adverse events were frequent but did not require hospitalization of any patient. No significant differences were found in incidence of adverse events related to BoNT-B dosing, medical fragility, or Gross Motor Function Classification System level. CONCLUSIONS: More than one-fourth of the children receiving BoNT-B injections had nonresponse, with most having previous nonresponse to onabotulinum toxin. Adverse events related to BoNT-B injections were frequent and unpredictable but not severe.
Assuntos
Antidiscinéticos/administração & dosagem , Antidiscinéticos/efeitos adversos , Paralisia Cerebral/tratamento farmacológico , Hipertonia Muscular/tratamento farmacológico , Adolescente , Toxinas Botulínicas/administração & dosagem , Toxinas Botulínicas/efeitos adversos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Criança , Pré-Escolar , Humanos , Injeções Intramusculares , Estudos RetrospectivosRESUMO
Botulinum toxin has been used for a variety of neuropathic conditions in diabetes mellitus. Meralgia paresthetica is a mononeuropathy of femoral nerve seen in diabetes and obesity with an unclear etiopathogenesis. We studied the role of botulinum toxin in resistant cases of meralgia paresthetica in type 2 diabetes.
Assuntos
Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Síndromes de Compressão Nervosa/tratamento farmacológico , Condução Nervosa/efeitos dos fármacos , Coxa da Perna/inervação , Adulto , Antidiscinéticos/administração & dosagem , Antidiscinéticos/efeitos adversos , Toxinas Botulínicas/administração & dosagem , Toxinas Botulínicas/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Neuropatia Femoral , Hemoglobinas Glicadas , Humanos , Injeções Intradérmicas , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/etiologia , Síndromes de Compressão Nervosa/fisiopatologia , Obesidade/complicações , Projetos Piloto , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/efeitos dos fármacos , Receptores de Glutamato/efeitos dos fármacos , Receptores da Neurocinina-1/efeitos dos fármacos , Resultado do TratamentoRESUMO
Local chemodenervation with botulinum toxin (BoNT) injections to relax abnormally contracting muscles has been shown to be an effective and well-tolerated treatment in a variety of movement disorders and other neurological and non-neurological disorders. Despite almost 30 years of therapeutic use, there are only few studies of patients treated with BoNT injections over long period of time. These published data clearly support the conclusion that BoNT not only provides safe and effective symptomatic relief of dystonia but also long-term benefit and possibly even favorably modifying the natural history of this disease. The adverse events associated with chronic, periodic exposure to BoNT injections are generally minor and self-limiting. With the chronic use of BoNT and an expanding list of therapeutic indications, there is a need to carefully examine the existing data on the long-term efficacy and safety of BoNT. In this review we will highlight some of the aspects of long-term effects of BoNT, including efficacy, safety, and immunogenicity.