Agonistas dopaminérgicos en la enfermedad de Parkinson / Dopaminergic agonists in Parkinson’s disease

Introducción: Los agonistas dopaminergicos no ergoticos (AD) son tratamientos útiles en la enfermedad de Parkinson (EP). Revisamos la farmacología, el grado de evidencia en cuanto a eficacia y tolerabilidad de pramipexol, ropinirol y rotigotina, y proponemos algunas recomendaciones para su uso en la practica clínica. Desarrollo: En el momento actual se dispone de formas de liberacion prolongada (LP) de pramipexol y ropinirol y de administración transdermica de rotigotina, que contribuyen a una mayor estabilidad plasmatica de los valores del fármaco. En la EP inicial los 3 fármacos mejoran de forma significativa las escalas de incapacidad de los pacientes, retrasan la aparición de discinesias y permiten retrasar la introducción de levodopa. En la EP avanzada reducen el tiempo off, mejoran la Unified Parkinson’s Disease Rating Scale (UPDRS) en on y en off y permiten reducir la dosis total de levodopa. Además, los 3 han sido capaces de inducir una mejora significativa en las escalas de la calidad de vida relacionada con la salud. Las formulas de LP han demostrado la no inferioridad frente a las de liberación inmediata, e incluso una mejor tolerabilidad (ropinirol). A pesar de su buen perfil de seguridad, entre los efectos adversos graves cabe destacar el trastorno de control de impulsos, cuya aparición puede ser precoz, y los accesos de sueño (sleep attacks). Aunque la terapia combinada no ha sido estudiada específicamente, algunas asociaciones (como la de apomorfina y otros AD) pueden ser beneficiosas. El cambio de un AD a otro es factible de un día para otro, aunque en los primeros días puede haber una sumación de efectos adversos dopaminergicos que debe tenerse en cuenta. La suspensión brusca del tratamiento con AD puede inducir un síndrome de deprivacion dopaminergica. La retirada de cualquier AD, en particular pramipexol, se ha asociado a aparición de apatía que puede ser grave. Conclusiones: Los nuevos AD no ergoticos constituyen una opción valida de tratamiento de la EP tanto inicial como avanzada. A pesar de su buen perfil de tolerabilidad, no están exentos de efectos adversos graves, que pueden tener un efecto atoplastico en la EP y que deben monitorizarse

Background: Non-ergoline dopamine agonists (DA) are effective treatments for Parkinson’s disease (PD). This review presents the pharmacology, evidence of efficacy and safety profile of pramipexole, ropinirole, and rotigotine, and practical recommendations are given regarding their use in clinical practice. Results: Extended-release formulations of pramipexole and ropinirole and transdermal continuous delivery rotigotine patches are currently available; these may contribute to stabilizing of plasma levels. In early PD, the three drugs significantly improve disability scales, delay time to dyskinesia and allow a later introduction of levodopa. In late PD they reduced total ’off’-time, improved Unified Parkinson’s Disease Rating Scale (UPDRS) in both ’on’ and ’off’ state and allowed a reduction in total levodopa dosage. A significant improvement in quality of life scales has also been demonstrated. Extended-release formulations have proved to be non-inferior to the immediate release formulations and are better tolerated (ropinirole). Despite a generally good safety profile, serious adverse events, such as impulse control disorder and sleep attacks, need to be routinely monitored. Although combination therapy has not been addressed in scientific literature, certain combinations, such as apomorphine and another DA, may be helpful. Switching from one DA to another is feasible and safe, although in the first days an overlap of dopaminergic side effects may occur. When treatment with DA is stopped abruptly, dopamine withdrawal syndrome may present. Suspending any DA, especially pramipexole, has been linked to onset of apathy, which may be severe. Conclusions: New non-ergotine DAs are a valuable option for the treatment of both early and late PD. Despite their good safety profile, serious adverse effects may appear; these effects may have a pathoplastic effect on the course of PD and need to be monitored

Dopaminergic agonists in Parkinson's disease.

BACKGROUND: Non-ergoline dopamine agonists (DA) are effective treatments for Parkinson's disease (PD). This review presents the pharmacology, evidence of efficacy and safety profile of pramipexole, ropinirole, and rotigotine, and practical recommendations are given regarding their use in clinical practice. RESULTS: Extended-release formulations of pramipexole and ropinirole and transdermal continuous delivery rotigotine patches are currently available; these may contribute to stabilising of plasma levels. In early PD, the three drugs significantly improve disability scales, delay time to dyskinesia and allow a later introduction of levodopa. In late PD they reduced total 'off'-time, improved Unified Parkinson's Disease Rating Scale (UPDRS) in both 'on' and 'off' state and allowed a reduction in total levodopa dosage. A significant improvement in quality of life scales has also been demonstrated. Extended-release formulations have proved to be non-inferior to the immediate release formulations and are better tolerated (ropinirole). Despite a generally good safety profile, serious adverse events, such as impulse control disorder and sleep attacks, need to be routinely monitored. Although combination therapy has not been addressed in scientific literature, certain combinations, such as apomorphine and another DA, may be helpful. Switching from one DA to another is feasible and safe, although in the first days an overlap of dopaminergic side effects may occur. When treatment with DA is stopped abruptly, dopamine withdrawal syndrome may present. Suspending any DA, especially pramipexole, has been linked to onset of apathy, which may be severe. CONCLUSIONS: New non-ergotine DAs are a valuable option for the treatment of both early and late PD. Despite their good safety profile, serious adverse effects may appear; these effects may have a pathoplastic effect on the course of PD and need to be monitored.

[Restless legs syndrome: detection, diagnosis, impact on health and utilization of health care resources]. / El síndrome de piernas inquietas: detección, diagnóstico, consecuencias sobre la salud y utilización de recursos sanitarios.

INTRODUCTION: Despite the high prevalence of Restless Legs Syndrome (RLS) reported, little information is available about this disorder in Spain. The present study was conducted to obtain information on this condition from patients identified by a simple screening questionnaire and subsequent diagnostic confirmation by the Primary Care Practitioner (PCP). MATERIALS AND METHODS: Three-stage, cross-sectional and retrospective (resource utilization), observational study in a sample of adult patients (2,047 subject) attending 10 outpatient Primary Care centers in Madrid, Barcelona and Valencia. A screening questionnaire containing the 4 RLS diagnostic criteria was used. Clinical assessment and RLS diagnosis confirmation was performed using a structured questionnaire. Other variables assessed were quality of life by SF-36 questionnaire scoring; sleep by the MOS sleep scale; symptom severity of RLS symptoms by the IRLS scales; health care resource utilization in the previous 12 months by completion of questionnaire following patient chart review. The diagnosis made by the PCP was confirmed in a small sample of patients by a neurologist expert in Movement Disorders. RESULTS: A total of 19.7% (404 out of 2,047) subjects positively answered the 4 diagnostic questions of the RLS screening questionnaire. Of these, 185 (9.0%) reported moderate to severe symptoms at least twice weekly. The PCP made a diagnosis of RLS in 79 of 154 patients completing the diagnostic interview. Thus, prevalence of RLS estimated in this adult population was 4.6%. The predictive value of the screening RLS questionnaire was 51.3%. Average age of symptom onset was 42 years (range: 20 - over 80 years). RLS symptoms were moderately (50.6%) or extremely (38%) distressing and 73.4% of RLS patients slept poorly at least two nights a week. This diagnosis represents 9.4% of all patients presenting to PCP and experiencing poor sleep. Mean score in the IRLS scale (0 - 40) was 19.4. Average score of SF-36 questionnaire (0-100) was 54.6, lower than the Spanish general reference population (61.4). About one third of the RLS patients had seen a physician because of RLS symptoms. However, a diagnosis was made in only 48% of these and only 5% the diagnosis was RLS. CONCLUSIONS: The DECODE RLS - Spain study shows that many patients with classical RLS symptoms frequently see their PCP without being adequately diagnosed and treated. Screening tools such as that used in this study may contribute to the detection of these patients.

El síndrome de piernas inquietas: detección, diagnóstico, consecuencias sobre la salud y utilización de recursos sanitarios / Restless legs syndrome: detection, diagnosis, impact on health and utilization of health care resources

Introducción: Pese a la elevada prevalencia del síndrome de piernas inquietas (SPI), se cuenta con escasa información sobre este trastorno en nuestro país. El objetivo de este estudio fue obtener información sobre este problema de salud a partir de pacientes identificados mediante un cuestionario de cribado y posterior confirmación diagnóstica por médicos de Atención Primaria (AP). Material y métodos: Estudio en tres etapas, transversal y retrospectivo (utilización de recursos), en una muestra de pacientes adultos (2.047 sujetos) que acudió a consultas ambulatorias de 10 centros de Atención Primaria (Madrid, Barcelona y Valencia). Se utilizó un cuestionario de detección con los 4 criterios diagnósticos de SPI. Se realizó la evaluación clínica y confirmación diagnóstica mediante un cuestionario estandarizado. Otras variables evaluadas fueron: calidad de vida, mediante la puntuación del Cuestionario SF-36 de salud; sueño, mediante la puntuación de la escala de sueño MOS; intensidad de los síntomas de SPI, mediante la puntuación de la escala IRLS; utilización de recursos sanitarios en los 12 meses previos. Confirmación del diagnóstico del médico de AP, por un neurólogo especialista en trastornos del movimiento en una muestra reducida aleatoria de pacientes. Resultados: Un 19,7% (404 de 2.047) de los sujetos respondió positivamente a las 4 preguntas diagnósticas del cuestionario de detección del SPI. De ellos, 185 sujetos (9,0%) presentaban síntomas por lo menos dos veces a la semana, de intensidad moderada a grave. El médico de AP confirmó el diagnóstico de SPI en 79 de los 154 pacientes que completaron la entrevista diagnóstica. La prevalencia en esta población adulta fue del 4,6%. El valor predictivo del cuestionario de detección del SPI fue de un 51,3%. La edad media de inicio de síntomas fue de 42 años (rango: 20-más de 80 años). Los síntomas de SPI fueron moderados en el 50,6% y graves en el 38%. El 73,4% de los pacientes con SPI dormía mal, al menos dos noches por semana. La puntuación media de la escala IRLS (0-40) fue de 19,4. La puntuación media del cuestionario SF-36 (0-100) fue de 54,6, más baja que la de la población española de referencia (61,4). Aproximadamente un tercio de los pacientes había consultado antes con un médico por los síntomas de SPI. No obstante, sólo un 48% contaba con un diagnóstico y sólo en un 5% éste era de SPI. Conclusiones: El estudio DECODE RSL indica que muchos pacientes con síntomas clásicos de SPI visitan frecuentemente a su médico de AP sin ser diagnosticados ni, por lo tanto, recibir un tratamiento adecuado. Herramientas como la utilizada en este estudio pueden ayudar a la detección de estos pacientes (AU)

Introduction: Despite the high prevalence of Restless Legs Syndrome (RLS) reported, little information is available about this disorder in Spain. The present study was conducted to obtain information on this condition from patients identified by a simple screening questionnaire and subsequent diagnostic confirmation by the Primary Care Practitioner (PCP). Materials and methods: Three-stage, cross-sectional and retrospective (resource utilization), observational study in a sample of adult patients (2,047 subject) attending 10 outpatient Primary Care centers in Madrid, Barcelona and Valencia. A screening questionnaire containing the 4 RLS diagnostic criteria was used. Clinical assessment and RLS diagnosis confirmation was performed using a structured questionnaire. Other variables assessed were quality of life by SF-36 questionnaire scoring; sleep by the MOS sleep scale; symptom severity of RLS symptoms by the IRLS scales; health care resource utilization in the previous 12 months by completion of questionnaire following patient chart review. The diagnosis made by the PCP was confirmed in a small sample of patients by a neurologist expert in Movement Disorders. Results: A total of 19.7% (404 out of 2,047) subjects positively answered the 4 diagnostic questions of the RLS screening questionnaire. Of these, 185 (9.0%) reported moderate to severe symptoms at least twice weekly. The PCP made a diagnosis of RLS in 79 of 154 patients completing the diagnostic interview. Thus, prevalence of RLS estimated in this adult population was 4.6%. The predictive value of the screening RLS questionnaire was 51.3%. Average age of symptom onset was 42 years (range: 20 - over 80 years). RLS symptoms were moderately (50.6%) or extremely (38%) distressing and 73.4% of RLS patients slept poorly at least two nights a week. This diagnosis represents 9.4% of all patients presenting to PCP and experiencing poor sleep. Mean score in the IRLS scale (0 - 40) was 19.4. Average score of SF-36 questionnaire (0-100) was 54.6, lower than the Spanish general reference population (61.4). About one third of the RLS patients had seen a physician because of RLS symptoms. However, a diagnosis was made in only 48% of these and only 5% the diagnosis was RLS. Conclusions: The DECODE RLS - Spain study shows that many patients with classical RLS symptoms frequently see their PCP without being adequately diagnosed and treated. Screening tools such as that used in this study may contribute to the detection of these patients (AU)