Baclofeno para o tratamento da espasticidade / Baclofen for or treatment of spasticity

INTRODUÇÃO: A espasticidade é caracterizada por ser um distúrbio motor relacionado a reflexos de estiramento tônico (tônus muscular) com espasmos tendinosos exagerados. É sintoma frequente de outras condições que afetam o sistema nervoso central (SNC), então a incidência e a prevalência variam de acordo com elas, bem como gravidade, músculos afetados, tempo de acometimento pela doença e tratamento. No Brasil, no âmbito do Sistema Único de Saúde (SUS), o tratamento da espasticidade é direcionado pelo Protocolo Clínico e Diretrizes Terapêuticas de Espasticidade (2017), cuja principal terapia farmacológica abordada é a toxina botulínica do tipo A. Tendo isso em vista e o fato do baclofeno ser uma tecnologia utilizada na clínica para casos de espasticidade, o presente relatório foi elaborado com o objetivo de compreender a viabilidade do uso de baclofeno de administração oral no manejo da espasticidade para pacientes adultos, visando a incorporação do fármaco no SUS. TECNOLOGIA: Baclofeno oral. PERGUNTA: O uso de baclofeno de administração oral é eficaz, seguro e custo-efetivo para o tratamento de espasticidade em pacientes adultos? EVIDÊNCIAS CLÍNICAS: Foi realizada uma revisão sistemática da literatura com o objetivo de identificar todos os estudos clínicos randomizados (ECRs) que avaliassem a eficácia e segurança do baclofeno oral em comparação com as terapias atualmente disponíveis no SUS para pacientes adultos com espasticidade. No total, foram incluídos 09 ECRs, sendo sete comparando o baclofeno com placebo e dois comparando o medicamento com diazepam. Na avaliação, não foi possível a condução de uma metanálise ou qualquer outro tipo de análise estatística que sintetize as informações apresentadas pelos ECRs devido à heterogeneidade dos estudos em relação aos desfechos e a forma de medi-los/relatá-los. Quando comparado ao placebo, apesar dos resultados de parte dos ECRs indicarem tendência de melhora com o baclofeno, a diferença de efeito não era estatisticamente significativa para certos desfechos. Em relação ao diazepam, nenhum estudo demonstrou diferença estatisticamente significativa entre os dois medicamentos no que diz respeito à melhora da espasticidade. Para todos dos desfechos de interesse analisados, os ECRs apresentaram alto risco de viés, principalmente por problemas relacionados às etapas de randomização, sigilo de alocação e cegamento (ausência de descrição ou relato inadequado). AVALIAÇÃO ECONÔMICA: Foi elaborado um modelo de custo-minimização no qual se considerou a mesma probabilidade de melhora da espasticidade do baclofeno oral mais terapia padrão e da terapia padrão isolada. A análise econômica conduzida baseou-se em um modelo de árvore de decisão que projetou a relação entre custo da intervenção (baclofeno oral + terapia padrão) e do comparador (terapia padrão) durante um ano. O resultado da análise de custo-minimização foi de aumento de custo com o tratamento com o baclofeno, sendo R$ 85,72 por paciente. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: A incorporação do baclofeno oral, no SUS, geraria um impacto incremental de R$ 955 mil no primeiro ano de incorporação, totalizando um incremento de R$ 4,7 milhões em 5 anos se a taxa de difusão for 30%. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: No horizonte considerado nesta análise, não foram detectadas tecnologias para o tratamento de espasticidade. CONSIDERAÇÕES FINAIS: Há limitação das evidências científicas que demonstram melhora da espasticidade com a utilização do baclofeno oral, o que pode ser, em parte, explicada pela data de condução dos estudos clínicos e do início da comercialização do medicamento na década de 1970. As limitações acabam por se estender para as análises econômicas, as quais foram baseadas em apenas um estudo clínico que não conseguiu demonstrar os benefícios clínicos do uso do medicamento. Por outro lado, o baclofeno apresentou um custo incremental relativamente baixo, de R$ 85,72 por paciente, em comparação à terapia padrão. Apesar das incertezas em relação à eficácia do baclofeno, ele é um medicamento de uso consolidado na prática clínica, para o qual não há evidência de eventos adversos graves, a sua dose tende a ser adaptada individualmente e, mesmo com a incerteza, diretrizes internacionais relatam que o seu uso é uma das alternativas terapêuticas para o tratamento da espasticidade. Além disso, entende-se que o impacto orçamentário incremental estimado da incorporação do baclofeno não afeta significativamente a sustentabilidade do SUS. RECOMENDAÇÃO PRELIMINAR DA CONITEC: O Plenário da Conitec, em sua 102ª Reunião Ordinária, realizada no dia 06 de outubro de 2021, deliberou que a matéria fosse disponibilizada em consulta pública com recomendação preliminar desfavorável à incorporação do baclofeno oral para o tratamento da espasticidade. Para essa recomendação, a Conitec considerou que a evidência clínica é escassa, de baixa qualidade e não é demonstrada a superioridade do medicamento em relação ao placebo. Apesar da larga experiência de uso e diretrizes internacionais citando o baclofeno oral como alternativa, essas recomendações não são suportadas por evidências. A matéria foi disponibilizada em Consulta Pública. CONSULTA PÚBLICA: Foi realizada entre os dias 04/11/2021 e 23/11/2021. Foram recebidas 22 constribuições, sendo quatro pelo formulário para contribuições técnico-científicas e 18 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Após apreciação de todas elas, o Plenário da Conitec entendeu que não houve argumentação suficiente para mudança de entendimento acerca de sua recomendação preliminar, que foi desfavorável à incorporação da tecnologia no SUS. RECOMENDAÇÃO FINAL DA CONITEC: Pelo exposto, o Plenário da Conitec, em sua 105ª Reunião Ordinária, no dia 10 de fevereiro de 2022, deliberou por unanimidade recomendar a não incorporação de baclofeno para o tratamento de pacientes adultos com espasticidade no SUS. Os membros da Conitec consideraram escassas as evidências científicas disponíveis, além de antigas e de não mostrar efeito benéfico muito superior ao comparador analisado. Lembraram dos valores pouco expressivos das análises de custo-efetividade e de impacto-orçamentário, mas isso não mudou a posição sobre a não incorporação. Por fim, foi assinado o Registro de Deliberação nº 711/2022. DECISÃO: Não incorporar o baclofeno oral para o tratamento da espasticidade, no âmbito do Sistema Único de Saúde ­ SUS, conforme a Portaria nº 25, publicada no Diário Oficial da União nº 52, seção 1, página 74, em 17 de março de 2022.

Access to Intrathecal Baclofen Treatment for Children with Cerebral Palsy in European Countries: An SCPE Survey Reveals Important Differences.

AIM: The aim is to study access to intrathecal baclofen (ITB) for children with cerebral palsy (CP) in Europe, as an indicator of access to advanced care. METHODS: Surveys were sent to CP registers, clinical networks, and pump manufacturers. Enquiries were made about ITB treatment in children born in 1990 to 2005 by sex, CP type, level of gross motor function classification system (GMFCS) and age at the start of treatment. Access to ITB was related to the country's gross domestic product (GDP) and % GDP spent on health. RESULTS: In 2011 population-based data from Sweden, Norway, England, Portugal, Slovenia, and Denmark showed that 114 (3.4%) of 3,398 children with CP were treated with ITB, varying from 0.4 to 4.7% between centers. The majority of the children were at GMFCS levels IV-V and had bilateral spastic CP. In Sweden, dyskinetic CP was the most commonly treated subtype. Boys were more often treated with ITB than girls (p = 0.014). ITB was reported to be available for children with CP in 25 of 43 countries. Access to ITB was associated with a higher GDP and %GDP spent on health (p < 0.01). Updated information from 2019 showed remaining differences between countries in ITB treatment and sex difference in treated children was maintained. CONCLUSION: There is a significant difference in access to ITB for children with CP across Europe. More boys than girls are treated. Access to ITB for children with CP is associated with GDP and percent of GDP spent on health in the country.

The use of off-label medications in substance abuse treatment programs.

Background: Substance use disorder (SUD) treatment centers serve a population of clients who have diverse needs, and may desire or require access to varied treatments while seeking care for their SUDs. While pharmacotherapies have increased in popularity for the treatment of SUDs, adoption rates do remain quite low. But a wider array of pharmacotherapies has become available in recent years which may shift the trend. This article helps shed light on how variations in SUD treatment centers develop and persist with regard to the adoption and delivery of off-label medications. Methods: We use a nationally representative and longitudinal sample of SUD treatment centers in the US (N = 196). We use a logistic regression to analyze the relationship between organizational characteristics and offering any medications, off-label. We also use a negative binomial regression to analyze the relationship between organizational characteristics and the number of medications that were used off-label. Results: Our findings reveal that older centers, accredited centers, and centers that offer mental health screenings are all positively associated with the provision of off-label medication in SUD treatment. We also find a positive relationship between private funding and offering a greater number of off-label medications. Conclusions: Our results suggest that SUD clients who seek treatment from centers that offer medications off-label, may have access to a greater number of medication-assisted treatment options.

The case for cautious consumption: NSAIDs in chronic kidney disease.

PURPOSE OF REVIEW: Strong epidemiological and pathologic evidence associates NSAIDs with kidney disease, both acute and chronic. Hence, the usage of NSAIDs has decreased in patients with, or at risk for, chronic kidney disease (CKD). Coupled with this has been a rise in use of opioids and other non-NSAID alternatives, which do come with significant, and underrecognized, risk of nonrenal adverse events. We review the literature to understand if this shift is appropriate or deleterious. RECENT FINDINGS: NSAIDs do have a low but tangible risk in causing acute kidney injury, electrolyte imbalances, and increasing blood pressure. However, their role in causing progressive kidney disease is due to long-term usage in high cumulative dosages, and the use of NSAIDs in combination with other agents. Alternatives such as opioids, tramadol, gabapentin and baclofen have weak evidence to support their use and strong evidence to show their harm in patients with CKD. SUMMARY: Tradeoffs are inherent in using active pharmaceuticals, and NSAIDs are no exception. Balancing potential benefits with possible adverse effects around pain management should be a part of every conversation for patients with kidney disease.

Baclofen in gamma-hydroxybutyrate withdrawal: patterns of use and online availability.

PURPOSE: Gamma-hydroxybutyrate (GHB) withdrawal is a life-threatening condition that does not always respond to standard treatment with benzodiazepines. Baclofen has potential utility as a pharmacological adjunct and anecdotal reports suggest that it is being used by drug users to self-manage GHB withdrawal symptoms. Here, we investigate current patterns of use and the online availably of baclofen. METHODS: Data triangulation techniques were applied to published scientific literature and publicly accessible Internet resources (grey literature) to assess the use of baclofen in GHB withdrawal. An Internet snapshot survey was performed to identify the availability of baclofen for online purchase and the compliance of retailers with the UK regulations. Data were collected according to pre-defined criteria. RESULTS: A total of 37 cases of baclofen use in GHB withdrawal were identified in the scientific literature, as well as 51 relevant discussion threads across eight Internet forums in the grey literature. Baclofen was available to purchase from 38 online pharmacies, of which only one conformed to the UK regulations. CONCLUSIONS: There is limited published evidence on the use of baclofen in GHB withdrawal, but both scientific and grey literature suggests clinical utility. Online pharmacies are readily offering prescription-only-medication without prescription and due to inadequate regulation, pose a danger to the public.

On-the-ground application of the 'temporary recommendation for use' regulatory measure on off-label use of baclofen for alcohol dependence in France: a regional survey of community pharmacies.

The 'temporary recommendation for use' (TRU) is a French novel regulatory measure for off-label drug. The first TRU to be issued by the French drug agency (in March 2014) pertained to the off-label use of baclofen for alcohol dependence (AD). We performed a questionnaire-based survey of the on-the-ground application of the baclofen TRU among community pharmacies in northern France. A pharmacist from 70 of the 219 pharmacies contacted (response rate: 32.0%) completed the questionnaire. The mean ± standard deviation number of off-label baclofen prescriptions for AD was 2.3 ± 2.2 per pharmacy per month. 65.2% of these prescriptions were issued by primary care physicians. 65.7% of the pharmacists had never seen 'TRU' written on the prescription, and 80.3% delivered a prescription without checking whether the patient had been included by the prescriber in the TRU. The main criterion used to identify off-label prescribing was the patient's medical history (according to 74.6% of pharmacists) and the prescription of an above-threshold dose (73.1%). 87.1% of the pharmacists were aware of the baclofen TRU, and 42.9% had actually read the document. 17.9% of the pharmacists estimated that the TRU had changed their attitude to off-label baclofen prescription, and 29.9% (20 out of 67) of them wanted to be more involved in the TRU process. Community pharmacists were well informed about the off-label use of baclofen for AD and the TRU. However, a majority of baclofen prescribers did not fulfill the TRU requirements while a majority of pharmacists did not exert any control over these off-label prescriptions. In practice, in 2015 the TRU measure had thus a limited impact on both the baclofen prescribing and delivery practices.

Cost-effectiveness of Intrathecal Baclofen Therapy in severe refractory non-focal disabling spasticity: a Spanish hospital perspective.

BACKGROUND: Current knowledge about long-term economic consequences of Intrathecal Baclofen Therapy (ITB Therapy®) is incomplete. METHODS: A markov model was developed to estimate long-term clinical and economic outcomes with ITB Therapy® and conventional medical management of severe refractory non-focal disabling spasticity. Clinical and cost inputs were obtained through a non-interventional, prospective, observational study in a Spanish neurorehabilitation hospital. RESULTS: ITB Therapy® increased remaining lifetime costs by €35,605 and resulted in a gain of 1.06 quality-adjusted life-years (QALYs), thus showing an incremental cost-effectiveness ratio (ICER) of €33,619/QALY gained. In alternative scenarios, reflecting other clinical settings and management options, considerably lower ICER values were obtained. In particular, opportunities were identified to improve efficiency by setting clinically and economically sound targets for post-operation length of stay. CONCLUSION: In the Spanish setting, ITB Therapy® resulted in an ICER close to €30,000/QALY gained; potential ways to reduce costs and further enhance efficiency can be identified.

Safety reports on the off-label use of baclofen for alcohol-dependence: recommendations to improve causality assessment.

INTRODUCTION: The off-label use of high-dose baclofen (HDB) for alcohol-dependence has recently spread. However, HDB has been associated with numerous reports of adverse events (AEs). Pharmacovigilance reporting is supposed to differentiate AEs from adverse drug reactions (ADRs), for which the causality of the drug is determined using validated methods. AREAS COVERED: Since 2010, we found 20 publications on baclofen-related AEs in alcohol dependence, in Medline-referenced journals or national pharmacovigilance reports. We focused on whether these reports used causality algorithms, and provided essential elements for determining baclofen causality and excluding the involvement of alcohol and other psychoactive substances or psychotropic drugs. In half of the cases, no causality algorithm was used. Detailed information on baclofen dosing was found in 17 out of 20 (85%) articles, whereas alcohol doses were given only in 10 (50%) publications. Other psychoactive substances and psychotropic drugs were broached in 14 (70%) publications. EXPERT OPINION: future publications reporting suspected HDB-induced ADRs should use validated causality algorithms and provide sufficient amount of contextual information for excluding other potential causes. For HDB, the psychiatric history, and the longitudinal description of alcohol consumptions and associated doses of psychoactive substances or psychotropic medications should be detailed for every reported case.

Eficácia, segurança e custo-efetividade do baclofeno oral e intratecal no tratamento da espasticidade na esclerose múltipla / Efficacy, safety and cost-effectiveness of oral and intrathecal baclofen in the treatment of multiple sclerosis spasticity / Eficacia, seguridad y coste-efectividad de baclofeno oral e intratecal en el tratamiento de espasmos en la esclerosis múltiple

TECNOLOGIA: Baclofeno oral, baclofeno via intratecal. INDICAÇÃO: Tratamento de espasmos na esclerose múltipla. CARACTERIZAÇÃO DA TECNOLOGIA: O baclofeno é um derivado do ácido gama-aminobutírico (GABA) e atua na inibição de estímulos nervosos na medula espinhal de modo a reduzir espasmos musculares. Existe nas apresentações oral na forma de comprimidos de 10mg e como implante cirúrgico de sistema contínuo de infusão intratecal ou bomba intratecal. PERGUNTA: O baclofeno é uma opção eficaz, segura e custo-efetiva a ser adotada no Sistema Único de Saúde (SUS) para o tratamento de espasmos na esclerose múltipla? BUSCA E ANÁLISE DE EVIDÊNCIAS CIENTÍFICAS: A busca por revisões sistemáticas (RS) de ensaios clínicos referentes à esclerose múltipla e baclofeno foi conduzida nas bases Medline (via Pubmed), Centre for Reviews and Dissemination, The Cochrane Library, EMBASE e LILACS. As Avaliações de Tecnologias de Saúde (ATS) foram pesquisadas em sites da Rede Brasileira de Avaliação de Tecnologias e Saúde (REBRATS) e das agências internacionais National Institute for Health and Care Excellence (NICE/Reino Unido), Health Technology Assessment Programme (NIHR/Reino Unido), Canadian Agency for Drugs and Technologies in Health (CADTH/Canadá), Agencias y Unidades de Evaluación de Tecnologías Sanitarias (AUnETS/Espanha) e Pharmaceutical Benefits Advisory Committee (PBAC/Austrália). A qualidade da evidência e força da recomendação foram avaliadas com o sistema GRADE. RESUMO DOS RESULTADOS DOS ESTUDOS SELECIONADOS: Foram incluídos oito estudos: seis RS e duas publicações de ATS. As RS não evidenciaram diferenças estatisticamente significantes entre baclofeno e diazepam ou tiazidina, contudo, alguns estudos identificaram diferença significante favorecendo o baclofeno em comparação com placebo. As RS incluídas recuperaram evidências de baixa ou moderada qualidade e, em grande parte, recomendaram fracamente a favor do baclofeno oral ou sem diferença estatística. Uma ATS recomendou infusão de baclofeno intratecal para pacientes com espasticidade grave e não responsivos ou tolerantes a terapia oral de baclofeno, sendo apontado como custo-efetivo. Outra ATS recomendou o uso de baclofeno oral como primeira linha de tratamento da espasticidade na esclerose múltipla. RECOMENDAÇÕES: Recomenda-se fracamente a favor do baclofeno oral para o tratamento de espasticidade em pacientes com esclerose múltipla. No mesmo sentido, recomenda-se fracamente a favor do uso de baclofeno intratecal para pacientes com espasticidade grave e refratários ou sem tolerância ao baclofeno oral. De acordo com os estudos encontrados não se verificou evidências que comprometam a segurança ou desabonem a utilização do baclofeno oral. A complexidade do manejo da doença e o baixo custo dessa forma farmacêutica também corroboram a recomendação do uso desta alternativa. Foi encontrada apenas uma revisão sistemática, de baixa qualidade, a qual sugeriu benefício do uso do baclofeno intratecal. A administração do medicamento intratecal pode auxiliar no manejo da espasticidade dolorosa em pacientes que não podem andar ou que perderam a funções do intestino e da bexiga. A forma farmacêutica injetável não apresenta registro no banco de dados da ANVISA. Não foi encontrado custo da implantação de bomba de infusão intratecal especificamente para o tratamento de espasticidade no SUS. Contudo, existe procedimento hospitalar na Relação Nacional de Ações e Serviços de Saúde (RENASES) para implante intratecal de bomba de infusão de fármacos para tratamento de dor crônica.(AU)

TECHNOLOGY: Oral baclofen, intrathecal baclofen. INDICATION: Treatment of spasms in multiple sclerosis. CHARACTERIZATION OF THE TECHNOLOGY: The Baclofen is a derivative of gamma-aminobutyric acid (GABA) and reduce muscle spasms by inhibition of nervous stimuli in the spinal cord. Oral presentations in 10 mg tablets and surgical implant system of continuous intrathecal infusion pump are available. QUESTION: Baclofen is the most effective, safety and cost-effective alternative to be adopted in the Brazilian Health System (SUS) for the treatment of spasms in multiple sclerosis? SEARCH AND ANALYSIS OF SCIENTIFIC EVIDENCE: We searched for systematic reviews (SR) of clinical trials related to multiple sclerosis and baclofen in Medline (via Pubmed), Centre for Reviews and Dissemination, The Cochrane Library, EMBASE and LILACS. We searched for Health Technology Assessments (HTA) in Brazilian Network for Technology Assessment (REBRATS) and the international agencies National Institute for Clinical Excellence and Health (NICE / UK), Health Technology Assessment Programme (NIHR / UK), Canadian Agency for Drugs and Technologies in Health (CADTH / Canada) Agencies y Evaluación Units Sanitary Technologies (AUnETS / Spain) and Pharmaceutical Benefits Advisory Committee (PBAC / Australia). The quality of evidence and strength of recommendation were evaluated by the GRADE system. SUMMARY OF RESULTS OF SELECTED STUDIES: We included eight studies: six SR and two HTA. The SR demonstrated no statistically significant differences between baclofen and diazepam or tiazidine. However, some studies have reported significant difference between baclofen compared to placebo. The SR included low or intermediate quality evidence with weak recommendation in favor of baclofen. One HTA recommend intrathecal infusion of baclofen for patients with severe spasticity and not responsive or tolerant to oral baclofen therapy, considered as cost-effective. Other HTA recommend oral baclofen as first-line therapy for spasticity in multiple sclerosis. Recommendations: We weakly recommended the use of oral baclofen for the treatment of spasticity in patients with multiple sclerosis. Similarly, we weakly recommended the use of intrathecal baclofen for patients with severe spasticity and refractory or intolerant to oral baclofen. According to the studies found there was no evidence that compromise the security or discredit the use of oral baclofen. The complexity of managing the disease and the low cost of this pharmaceutical form also support the recommendation to use this alternative. We included only one systematic review of low quality, which suggested benefit of using intrathecal baclofen. Intrathecal administration of the medicine may assist in management of painful spasticity for patients who can not walk, or who lost their bowel and bladder functions. There is no injectable bacofen licensed in Brazil. We did not find the cost of intrathecal infusion pump implantation specifically for the treatment of spasticity in SUS. However, there is hospital procedure in National List of Actions and Health Services (RENASES) for intrathecal implantation of drug infusion pump for the treatment of chronic pain.(AU)

TECNOLOGÍA: baclofeno oral, baclofeno intratecal. INDICACIÓN: Tratamiento de espasmos en la esclerosis múltiple. CARACTERIZACIÓN DE LA TECNOLOGÍA: Baclofen es un derivado de ácido gamma-aminobutírico (GABA) y actúa sobre la inhibición de estímulos nerviosos en la médula espinal para reducir los espasmos musculares. Está disponible en presentaciones orales en comprimidos de 10 mg y como un sistema de implante quirúrgico para perfusión intratecal continua o bomba intratecal. PREGUNTA: ¿El baclofeno es una opción eficaz, seguro y rentable que debe adoptarse en el Sistema Único de Salud (SUS) para el tratamiento de los espasmos en la esclerosis múltiple? BÚSQUEDA Y ANÁLISIS DE LA EVIDENCIA CIENTÍFICA: Se realizó la búsqueda de revisiones sistemáticas (RS) de los ensayos clínicos relacionados con la esclerosis múltiple y el baclofeno en Medline (a través de Pubmed), Centre for Reviews and Dissemination, The Cochrane Library, EMBASE e LILACS. Las Evaluaciones de Tecnologías Sanitarias (ETS) se investigaron en la Rede Brasileira de Avaliação de Tecnologias e Saúde (REBRATS) y organismos internacionales National Institute for Health and Care Excellence (NICE/Reino Unido), Health Technology Assessment Programme (NIHR/Reino Unido), Canadian Agency for Drugs and Technologies in Health (CADTH/Canadá), Agencias y Unidades de Evaluación de Tecnologías Sanitarias (AUnETS/Espanha) e Pharmaceutical Benefits Advisory Committee (PBAC/Austrália). La calidad de la evidencia y la fuerza de la recomendación se evaluaron con el sistema GRADE. RESUMEN DE LOS RESULTADOS DE LOS ESTUDIOS SELECCIONADOS: Se incluyeron ocho estudios: seis RS y dos publicaciones de ATS. La RS no mostraron diferencias estadísticamente significativas entre el baclofeno y diazepam o tiazidina. Sin embargo, algunos estudios han identificado diferencias significativas de baclofeno en comparación con placebo. La RS incluyen pruebas de calidad baja o moderada y en gran medida que debe adoptarse de la tecnología débilmente recomendado o indican que no hay diferencia estadística. Una ATS recomienda la infusión intratecal de baclofeno para pacientes con espasticidad severa y que no responden o tolerantes a la terapia de baclofeno oral, siendo considerado como Costo efectivo. Otra ATS recomienda el uso de baclofeno oral como tratamiento de primera línea de la espasticidad en la esclerosis múltiple. RECOMENDACIONES: Se recomienda débilmente a favor de baclofeno oral para el tratamiento de la espasticidad en pacientes con esclerosis múltiple. Del mismo modo, se recomienda débilmente en favor del uso de baclofeno intratecal en pacientes con espasticidad severa y refractaria o sin tolerancia al baclofeno oral. De acuerdo con los estudios encontrados no hay pruebas que comprometen la seguridad o desacrediten el uso de baclofeno oral. La complejidad de la gestión de la enfermedad y el bajo costo de esta forma farmacéutica también apoyan la recomendación de utilizar esta alternativa. Sólo se encontró una revisión sistemática de baja calidadque sugería beneficio del uso de baclofeno intratecal. La administración intratecal de medicamento puede ayudar en el tratamiento de la espasticidad dolorosa para los pacientes que no pueden caminar, o que perdieron sus funciones intestinales y de la vejiga. La forma de farmacéutica inyectable no presenta registro en Brasil. No se ha encontrado coste de implantación de la bomba de infusión intratecal específicamente para el tratamiento de la espasticidad en SUS. Sin embargo, hay procedimiento de hospital en la Lista Nacional de Acciones y Servicios de Salud (RENASES) para la implantación de la bomba de infusión intratecal de medicamentos para el tratamiento del dolor crónico.(AU)

Cost-effectiveness analysis of baclofen and chlordiazepoxide in uncomplicated alcohol-withdrawal syndrome.

OBJECTIVES: Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acidB (GABAB) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS. MATERIALS AND METHODS: This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient's perspective and third-party perspective. RESULTS: The average cost-effectiveness ratio (ACER) in patient's perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03). CONCLUSION: Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide.

Off-label baclofen prescribing practices among French alcohol specialists: results of a national online survey.

OBJECTIVE: To evaluate, among alcohol specialists belonging to the Société Française d'Alcoologie (SFA), i.e., the French Alcohol Society, the proportion of physicians who prescribed off-label baclofen for alcohol use disorders (AUDs). The secondary objective was to depict the features of individual prescribing and monitoring practices. METHODS: On-line survey among 484 French alcohol specialists. Physicians were asked whether they prescribed baclofen for AUDs. If they did not, the reasons for this choice were investigated. If they did, the features of the physician's prescribing practice were explored, including the number of patients treated, the mean and maximum doses, the monitoring precautions and the pharmacovigilance reporting. Participants were also asked about their empirical findings on HDB's efficacy and safety. RESULTS: In total, 302 physicians (response rate of 62.4%) participated in the survey. Data from 296 participants were analysed, representing 59.4% of all active prescribing physicians belonging to the SFA. HDB use was declared by 74.6% of participants (mean dose 109.5 ± 43.6 mg/d; maximum dose 188 ± 93.3 mg/d). However, 79.2% of prescribers had treated less than 30 patients, and 67.8% used HDB as a second-line medication. Although HDB was perceived as more efficacious than approved drugs by 54.3% of prescribers, it was also declared less safe by 62.8%. Nonetheless, 79.7% of prescribers had never filed any pharmacovigilance report. Non-prescribers (25.6%) were primarily deterred by the current lack of scientific data and official regulation. CONCLUSION: A majority of French alcohol specialists reported using HDB, although often on a limited number of their patients. HDB was considered efficacious but also potentially hazardous. Despite this, physicians reported minimal safety data to the health security system. While French health authorities are planning to draft a specific regulatory measure for framing off-label HDB prescribing practices, the sustained education of prescribers on spontaneous pharmacovigilance reporting should be enhanced.

Costs and quality of life in multiple sclerosis patients with spasticity.

BACKGROUND: The resource use and health-related quality of life (HRQoL) of patients with multiple sclerosis (MS) spasticity are not well known. The purpose of this study was to obtain estimates of resource utilization, costs, and HRQoL, for patients with different levels of MS spasticity in southern Sweden. MATERIAL AND METHODS: Cross-sectional data on spasticity severity (using a Numerical Rating Scale, NRS), resource use and HRQoL (using EQ-5D) were collected using a patient questionnaire and chart review. Patients were recruited through a clinic in southern Sweden. The study reviews direct medical, direct non-medical and indirect costs. RESULTS: Total costs were estimated to €114,293 per patient and year. Direct medical costs (€7898) accounted for 7% of total costs. Direct non-medical costs (€68,509) accounted for 60% of total costs. Total costs increased with severity of spasticity: for patients with severe spasticity, the total cost was 2.4 times greater than those for patients with mild spasticity. HRQoL decreased as spasticity increases. CONCLUSION: The results of this study show that MS spasticity is associated with a substantial burden on society in terms of costs and HRQoL.

[A system of prescriptions without drug approval: example of baclofen]. / Un dispositif de prescriptions hors-AMM : exemple du baclofène.

Baclofen is an anti-spastic drug that acts as an agonist of GABA-B receptors. It also seems to decrease the appetence for alcohol (anti-craving effect), although this effect has not been certified by Authorities for drug approval in France (AMM). However, baclofen receives a great deal of demand by patients hoping to reduce their alcohol consumption. Nonetheless, the lack of AMM and the high doses of baclofen supposed to exert an anti-craving effect often discourage practitioners from prescribing this drug in current medical practice. Therefore, it is preferable for a drug like baclofen to be prescribed under specific regulations. As such, certain criteria similar to those required in clinical trials are necessary to protect patients as well as the prescribing doctors. The criteria that are proposed here are: the use of drugs without AMM approval as a last resort (all other treatments must have failed), the collegiate decision for the drug prescription, good knowledge of the potency of the drug as well as good record keeping of patients and proper supervision. The departments of addiction, pharmacology and pharmacovigilance of the University Hospital of Lille, France present here a medical process named "multidisciplinary consultations for resort treatments of addictions" (CAMTEA). This process is designed to meet all the above mentioned criteria and to allow the use of baclofen as an anti-craving drug in safest conditions. If this proves to be successful with baclofen, it is possible to extend the use of CAMTEA to other drugs without AMM approval in addictologic pathologies.

The GABA B agonist baclofen reduces cigarette consumption in a preliminary double-blind placebo-controlled smoking reduction study.

The surge in dopamine in ventral striatal regions in response to drugs of abuse and drug-associated stimuli is a final common pathway of addiction processes. GABA B agonists exert their effects indirectly, by quieting dopaminergic afferents. The ability of the GABA B agonist, baclofen to ameliorate nicotine and drug motivated behavior is established within the animal literature, however its potential to do so in humans is understudied, particularly with respect to its possible utility as a smoking cessation agent. We conducted a nine-week double-blind placebo-controlled pilot trial of baclofen for smoking reduction (N=30/group) in smokers contemplating, but not quite ready to quit. Baclofen was titrated upwards to 20mg q.i.d. over a period of twelve days. The primary outcome measure was the number of cigarettes smoked per day (CPD). A significant group by time effect of medication was observed. Baclofen was superior to placebo in reducing CPD (beta=0.01, t=1.97, p<0.05). The most common side effect reported during baclofen treatment is transient drowsiness, however there were no differences between groups in mild, moderate, or severe sedation. Craving was significantly lowered at end of treatment in all smokers (p<0.02). Retention did not differ between groups. In line with a multitude of preclinical studies examining the effects of baclofen on drug-motivated behavior, baclofen reduced CPD. In agreement with other studies examining craving and drug use, reductions in CPD were accompanied by a reduction in craving, a major motivator underlying continued smoking and relapse. These preliminary results demonstrate provisional evidence of the utility of baclofen to aid in smoking cessation and indicate further investigation.

Cost-effectiveness modeling of intrathecal baclofen therapy versus other interventions for disabling spasticity.

OBJECTIVE: To assess by simulation the cost-effectiveness of intrathecal baclofen (ITB) therapy compared with conventional medical treatments for patients with disabling spasticity and functional dependence caused by any neurological disease. METHODS: Two models were created to simulate therapeutic strategies for managing severe spasticity, one with and one without the use of ITB, to assess various treatment sequences over 2 years based on current medical practices in France. Successful treatment at each evaluation was defined as a combination of: (1) the increased patient and caregiver satisfaction as assessed by goal attainment scaling (GAS), and (2) a decrease of at least 1 point on the Ashworth score. Probabilistic sensitivity analyses were performed using 5000 Monte-Carlo simulations taking into account specific distribution curves for direct costs and effectiveness parameters in each treatment option. RESULTS: The model simulations suggest that including ITB as a first option strategy in the management of function of severely impaired patients with disabling spasticity results in a higher success rate (78.7% vs 59.3%; P < .001). In addition, the ITB therapy model revealed a lower cost (pound 59,391 vs pound 88,272; P < .001) and an overall more favorable cost-effectiveness ratio (pound 75,204/success vs pound 148,822/success; P < .001), compared with conventional medical management without ITB. CONCLUSION: Within the assumptions of our modeling, ITB therapy evaluated by a combination of treatment success criteria at 6-month intervals over a 2-year period may be a cost-effective strategy compared to conventional medical management alone.

Intrathecal baclofen therapy in children with intractable spastic cerebral palsy: a cost-effectiveness analysis.

In a Dutch national study, we recently established the effectiveness and safety of continuous intrathecal baclofen infusion (CITB) in children with intractable spastic cerebral palsy (CP). Because prospective studies on the cost-effectiveness of CITB in children with spastic CP are lacking, we conducted a cost-effectiveness analysis alongside our prospective national study. We compared the costs and health effects of CITB with those of standard treatment only, from the health care perspective for a 1-year period. Health effects were expressed in terms of a visual analogue scale for individual problems and quality-adjusted life years (QALYs). We included eight females and seven males, aged between 7 and 17 years (mean age 13y 8mo [SD 3y]). Eleven children had spastic CP and four had spastic-dyskinetic CP. One child was clsssified on the Gross Motor Function Classification System at Level III, two at Level IV, and 12 at Level V. CITB was more effective and more costly than standard treatment only. Gaining one QALY cost on average 32,737 euros. We conclude that based on the threshold-willingness to pay for one QALY in the Netherlands (80,000 euros), our results confirm the cost-effectiveness of CITB for carefully selected children with intractable spastic CP.

Intrathecal baclofen therapy: challenges in patients with multiple sclerosis.

Intrathecal baclofen (ITB) is a recognized therapy for severe spasticity of both spinal and cerebral origin, with documented positive clinical outcomes for many patients with multiple sclerosis (MS). This article reviews some specific considerations concerning the use of ITB in the MS population, based on the author's 10 years of clinical experience. The unpredictable and progressive nature of the disease affects the identification of appropriate goals, the patient's decision-making process, and the evaluation of the response to the treatment over time. Patients with MS may be more sensitive to intrathecal baclofen than patients with other diagnoses, and may need a lower dose for both the screening test and maintenance therapy. Subtle cognitive changes may affect the patient's ability to understand the education needed for successful management of ITB. Some practical strategies are offered for the nurse involved in the care of these patients in each stage of the therapy.