AIM: To compare the efficacy and safety of prednisolone/prednisone and adrenocorticotropic hormone (ACTH) in the treatment of infantile spasms using a meta‐analysis of randomized controlled trials (RCTs). METHOD: In a systematic literature search of electronic databases (MEDLINE, Embase, the Cochrane Library), we identified RCTs that assessed prednisolone/prednisone compared with ACTH/tetracosactide in patients with infantile spasms. The electroclinical response and adverse events were evaluated. RESULTS: Six RCTs (616 participants) were included in the meta‐analysis. Compared with prednisolone/prednisone, ACTH/tetracosactide was not superior in terms of cessation of spasms at day 14 (relative risk 1.19, 95% confidence interval [CI] 0.74–1.92), day 42 (relative risk 1.02, 95% CI 0.63–1.65), and resolution of hypsarrhythmia on electroencephalogram (relative risk 1.14, 95% CI 0.71–1.81); the incidences of common adverse reactions caused by ACTH/tetracosactide were not lower than that of prednisolone/prednisone for irritability (relative risk 0.79, 95% CI 0.57–1.10), increased appetite (relative risk 0.78, 95% CI 0.57–1.08), weight gain (relative risk 0.86, 95% CI 0.56–1.32), and gastrointestinal upset (relative risk 0.60, 95% CI 0.35–1.02), though it seemed less frequent. INTERPRETATION: Prednisolone/prednisone elicits a similar electroclinical response as ACTH for infantile spasms, which indicates that it can be an alternative to ACTH for treating infantile spasms. What this paper adds Prednisolone/prednisone is as effective as adrenocorticotropic hormone (ACTH) in electroclinical response of infantile spasms. Prednisolone/prednisone and ACTH cause similar and tolerable adverse effects, whose incidences are comparable. High‐dose prednisone/prednisolone might be preferable to low dose for achieving freedom from spasms. (PsycInfo Database Record (c) 2020 APA, all rights reserved)
OBJECTIVE: To compare the effect and safety of prednisolone and adrenocorticotropic hormone (ACTH) in the treatment of infantile spasms (IS).
METHODS: Cochrane Library, Embase, PubMed, China Biology Medicine Disc, CNKI, and Wanfang Data were searched for clinical studies on the comparison between prednisolone and ACTH in the treatment of IS. Literature screening, data extraction, and quality assessment were performed. Review Manager 5.3 was used for Meta analysis.
RESULTS: Five clinical studies were included according to the inclusion criteria and exclusion criteria. Meta analysis showed that there was no significant difference in the spasm remission rate, spasm remission time, complicating infection rate, and irritability rate between the prednisolone and ACTH treatment groups (P>0.05), but the disappearance rate of hypsarrhythmia in the electroencephalogram was higher in the ACTH treatment group than in the prednisolone treatment group (P<0.05).
CONCLUSIONS: The available evidence shows no difference in the clinical efficacy of prednisolone versus ACTH in the treatment of IS. However, ACTH is superior to prednisolone in stabilizing EEG. The two therapies have no difference in the incidence of adverse reactions such as infection and irritability.
OBJECTIVE: To compare the therapeutic effectiveness of oral corticosteroids with that of adrenocorticotrophic hormone for infantile spasms.
METHODS: PubMed, Embase, Scopus, and the Cochrane library were searched to retrieve studies published before December 2018 to identify pediatric patients with a diagnosis of infantile spasms. The interventions of oral corticosteroids and adrenocorticotrophic hormone were compared. We included only randomized controlled trials that reported the cessation of spasms as treatment response. The primary outcome was clinical spasm cessation on day 13 or 14. The secondary outcomes were the resolution of hypsarrhythmia, side effects, continued spasm control, spasm relapse rate, and subsequent epilepsy rate. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the study-level quality assessment was conducted using the Cochrane risk-of-bias tool.
RESULTS: After extensive review, 39 articles were included for meticulous evaluation. Five randomized controlled trials with a total of 239 individuals were eligible for further analysis. No significant difference was detected between the corticosteroids and adrenocorticotrophic hormone in the cessation of clinical spasms (odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.16 to 1.81; P = 0.32). The subgroups of high-dose prednisolone versus adrenocorticotrophic hormone and low-dose prednisone versus adrenocorticotrophic hormone also exhibited no significant difference. Furthermore, the two subgroups did not differ in terms of hypsarrhythmia resolution, side effects, relapse rate, or subsequent epilepsy rate.
INTERPRETATION: This meta-analysis suggests that high-dose prednisolone is not inferior to adrenocorticotrophic hormone and that it be considered a safe and effective alternative treatment.
BACKGROUND: This is an updated version of the Cochrane Review previously published in the Cochrane Database of Systematic Reviews 2015, Issue 10. Epilepsy is a common neurological condition, characterised by recurrent seizures. Most people respond to conventional antiepileptic drugs, however, around 30% will continue to experience seizures, despite treatment with multiple antiepileptic drugs. Sulthiame, also known as sultiame, is a widely used antiepileptic drug in Europe and Israel. We present a summary of the evidence for the use of sulthiame as add-on therapy in epilepsy.
OBJECTIVES: To assess the efficacy and tolerability of sulthiame as add-on therapy for people with epilepsy of any aetiology compared with placebo or another antiepileptic drug.
SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and CENTRAL (17 January 2019), MEDLINE Ovid (1946 to January 16, 2019), ClinicalTrials.gov and the WHO ICTRP Search Portal (17 January 2019). We imposed no language restrictions. We contacted the manufacturers of sulthiame, and researchers in the field to seek any ongoing or unpublished studies.
SELECTION CRITERIA: Randomised controlled trials of add-on sulthiame, with any level of blinding (single, double or unblinded) in people of any age, with epilepsy of any aetiology.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, and extracted relevant data. We assessed these outcomes: (1) 50% or greater reduction in seizure frequency between baseline and end of follow-up; (2) complete cessation of seizures during follow-up; (3) mean seizure frequency; (4) time-to-treatment withdrawal; (5) adverse effects; and (6) quality of life. We used intention-to-treat for primary analyses. We presented results as risk ratios (RR) with 95% confidence intervals (CIs). However, due to the paucity of trials, we mainly conducted a narrative analysis.
MAIN RESULTS: We included one placebo-controlled trial that recruited 37 infants with newly diagnosed West syndrome. This trial was funded by DESITIN Pharma, Germany. During the study, sulthiame was given as an add-on therapy to pyridoxine. No data were reported for the outcomes: 50% or greater reduction in seizure frequency between baseline and end of follow-up; mean seizure frequency; or quality of life. For complete cessation of seizures during a nine-day follow-up period for add-on sulthiame versus placebo, the RR was 11.14 (95% CI 0.67 to 184.47; very low-certainty evidence), however, this difference was not shown to be statistically significant (P = 0.09). The number of infants experiencing one or more adverse events was not significantly different between the two treatment groups (RR 0.85, 95% CI 0.44 to 1.64; very low-certainty evidence; P = 0.63). Somnolence was more prevalent amongst infants randomised to add-on sulthiame compared to placebo, but again, the difference was not statistically significant (RR 3.40, 95% CI 0.42 to 27.59; very low-certainty evidence; P = 0.25). We were unable to conduct meaningful analysis of time-to-treatment withdrawal and adverse effects due to incomplete data.
AUTHORS' CONCLUSIONS: Sulthiame may lead to a cessation of seizures when used as an add-on therapy to pyridoxine in infants with West syndrome, however, we are very uncertain about the reliability of this finding. The included study was small and had a significant risk of bias, largely due to the lack of details regarding blinding and the incomplete reporting of outcomes. Both issues negatively impacted the certainty of the evidence. No conclusions can be drawn about the occurrence of adverse effects, change in quality of life, or mean reduction in seizure frequency. No evidence exists for the use of sulthiame as an add-on therapy in people with epilepsy outside West syndrome.Large, multi-centre randomised controlled trials are needed to inform clinical practice, if sulthiame is to be used as an add-on therapy for epilepsy.
The aim of this systematic review was to collect and analyze all the RCTs and observational studies investigating the efficacy of ketogenic diet (KD) in infantile spasms (IS) patients after a 1- to 6-month follow-up period, in terms of decrease in seizure frequency of >50% or a seizure-free interval. Moreover, the potential effect of gender, IS etiology, age at onset of IS, and age at start of KD have been investigated. Finally, we evaluated the seizure-free rate at 12 and 24 months of follow-up. In June 2016, a computer search was performed on MedLine (PubMed), EMBASE, and the Cochrane Library. Only, English language studies conducted after 1980 and those reporting in detail the variation in seizure frequency have been selected. Thirteen observational studies (341 patients) were included in the final analysis. A median rate of 64.7% of patients experienced a spasm reduction >50% (IQR: 38.94%). The median spasm-free rate was 34.61% (IQR: 37.94%). IS of unknown etiology seemed to have an increased probability of achieving freedom from seizures (RR: 1.72, 95%CI: 1.18-2.53). Long-time follow-up data revealed a median seizure-free rate of 9.54% (IQR: 18.23%). Although the literature is still lacking in high-quality studies, which could provide a stronger level evidence, our findings suggest a potential benefit of KD for drugresistant IS patients.
OBJECTIVE: To estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0-18 years).
METHODS: Using the Embase and MEDLINE databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed-age populations. According to the PRISMA network meta-analysis guideline, the study-level quality assessment was made with the Cochrane risk-of-bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or ≥50% seizure reduction.
RESULTS: We selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [OR] = 3.3, 95% credible interval [CrI] = 1.3-7.6) and perampanel (OR = 2.5, 95% CrI = 1.1-5.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The OR point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow-up was observed among the studies.
SIGNIFICANCE: This network meta-analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow-up length, and more reliable inclusion criteria.
Implementation of international guidelines for the treatment of epileptic spasms, is challenging when access to adrenocorticotrophic hormone (ACTH) and vigabatrin is restricted, especially in Low and Middle Income Countries (LMIC). Oral corticosteroids are alternative interventions but evidence for the optimal agent, dose, duration, efficacy and long-term effects is lacking. A systematic review of the literature was performed to assess the quality of evidence of prednisone and prednisolone (oral corticosteroids) for the management of epileptic spasms. There is level C recommendation based on class III evidence to support the efficacy of oral corticosteroids for the acute clinical control of epileptic spasms and EEG resolution. Efficacy of oral corticosteroids in comparison to the internationally recommended intervention of ACTH has class IV evidence supporting level U recommendation. Similarly, there is no data on the risk of relapse with oral corticosteroids (class IV, level U), compared to ACTH. There is class IV evidence supporting level U recommendation for the safety of oral corticosteroids and class II evidence for level B recommendation for ACTH. In terms of oral corticosteroids and effects on long-term development there is class IV evidence leading to level U recommendation, compared to class III evidence supporting level C recommendation for ACTH. Randomized controlled studies are needed to compare oral corticosteroids with ACTH, the optimal dosage and regimen as well as the long-term neurodevelopmental outcomes. Based on the limited existing studies a treatment guideline for LMIC is proposed which could be used to standardize interventions permitting clarification of these unmet questions.
OBJECTIVES: West syndrome (also known as infantile spasm because of its main seizure type) is a rare form of epilepsy that begins during early infancy. Recent guidelines and reviews on West syndrome recommend the use of adrenocorticotropic hormone steroids, or vigabatrin, as the first-line treatment. However, West syndrome remains to be one of the most challenging epilepsies to treat. Here, we systematically reviewed the current literature obtained during the previous decade. This article provides an overview of the current treatment of infantile spasms. METHODS: PubMed and EMBASE were searched to retrieve studies on human published during 2005–2015 and to identify patients with clinical diagnosis of infantile spasms. Drug or diet treatments were used as interventions and comparators. RESULTS: We included 55 studies, of which 1 study was a meta-analysis, 9 were randomized controlled trials, 21 were prospective studies, and 24 were retrospective studies. Topiramate, levetiracetam, zonisamide, and sodium valproate with benzodiazepine (clonazepam or nitrazepam) were found to be potential drugs for treating West syndrome besides adrenocorticotropic hormone, steroids, and vigabatrin. Ketogenic diet and modified Atkins diet were also found to be effective. CONCLUSIONS: To date, data regarding the efficacy of treatments of West syndrome still remain limited. Some treatments, including topiramate and ketogenic diet, seem promising besides adrenocorticotropic hormone, steroids, and vigabatrin. Well-designed trials are warranted to validate the findings. (PsycInfo Database Record (c) 2023 APA, all rights reserved)
ANTECEDENTES: de corta duración corticosteroides orales se utilizan comúnmente en los niños, pero se sabe que están asociados con reacciones adversas a medicamentos (RAM). Esta revisión tuvo como objetivo identificar las reacciones adversas más comunes y graves y para determinar sus niveles de riesgo relativo.
Métodos: Se realizó una búsqueda bibliográfica en EMBASE, MEDLINE, International Pharmaceutical Abstracts, CINAHL, Cochrane Library y en PubMed se llevó a cabo sin restricciones de idioma para identificar estudios en los que los corticosteroides orales se administran a los pacientes a partir de 28 días a 18 años de edad de hasta e incluyendo 14 días de tratamiento. Cada base de datos se realizaron búsquedas de sus fechas más tempranas de diciembre de 2013. Se incluyeron todos los estudios que proporcionen información clara sobre las ADR.
RESULTADOS: Treinta y ocho estudios que incluyeron 22 ensayos controlados aleatorios (ECA) cumplieron los criterios de inclusión. Los estudios incluyeron un total de 3200 niños en los que se reportaron 850 reacciones adversas. Las tres reacciones adversas más frecuentes fueron vómitos, cambios de conducta, trastornos del sueño, con sus respectivas tasas de incidencia de 5,4%, 4,7% y 4,3% de los pacientes evaluados para estas reacciones adversas. La infección fue una de las reacciones adversas más graves; un niño murió después de contraer la varicela zoster. Cuando se mide, 144 de 369 pacientes mostraron un aumento de la presión arterial; 21 de 75 pacientes mostraron un aumento de peso; y la supresión del eje hipotálamo-pituitario-adrenal bioquímica se detectó en 43 de 53 pacientes.
CONCLUSIONES: vómitos, cambios de comportamiento y trastornos del sueño fueron las reacciones adversas más frecuentes vistos cuando se les dio de corta duración corticosteroides orales para los niños. Aumento de la susceptibilidad a la infección fue el más grave ADR.
PRUEBA NÚMERO DE REGISTRO: CRD42014008774. Por registro prospectivo PROSPERO Internacional de las revisiones sistemáticas.
ANTECEDENTES: Los espasmos infantiles (síndrome del Oeste) es un síndrome que se incluye un tipo peculiar de convulsión epiléptica, los espasmos-y una anormalidad electroencefalográfica (EEG), a menudo llamado hipsarritmia. Retraso psicomotor se encuentra con frecuencia en el seguimiento. Aproximadamente dos tercios de los niños afectados tendrán detectable anormalidad neurológica subyacente, pero aún se sabe poco sobre la base fisiopatológica de los espasmos infantiles, y el tratamiento sigue siendo problemática.
OBJETIVOS: Comparar los efectos de fármacos únicos utilizados para tratar los espasmos infantiles en términos de control de los espasmos, la resolución de las tasas de EEG, recaída, desarrollo psicomotor, epilepsia posterior, los efectos secundarios y la mortalidad.
ESTRATEGIA DE BÚSQUEDA: Identificar los datos publicados, se realizaron búsquedas en el Grupo Cochrane de Epilepsia en el Registro Especializado (octubre de 2012), CENTRAL (The Cochrane Library 2012, número 9), MEDLINE (1946 hasta septiembre, semana 4, 2012), EMBASE (1980 a marzo de 2003) y las listas de referencia de todos los artículos recuperados.
Para identificar datos no publicados, se realizaron búsquedas en el Registro ISRCTN (www.controlled-trials.com), mantuvo correspondencia con colegas y compañías farmacéuticas, e hicimos peticiones en las conferencias internacionales.
Criterios de selección: Todos los ensayos controlados aleatorios (ECA) de la administración del tratamiento farmacológico de los pacientes con espasmos infantiles.
Recopilación y análisis de datos: La recolección de datos de todas las publicaciones relevantes se llevó a cabo de forma independiente por tres revisores (antes de 2010) o por dos revisores mediante una proforma estándar. El análisis incluyó la evaluación de la calidad del estudio y la búsqueda de fuentes de heterogeneidad.
Resultados principales: Se encontraron 16 ECA pequeños (menos de 100 pacientes incluidos) y 2 ECA más grandes (más de 100 pacientes incluidos). 18 Estos estudios examinaron un total de 916 pacientes tratados con un total de 12 agentes farmacéuticos diferentes. Metodología general de los estudios fue deficiente, en parte debido a los dilemas éticos como la aplicación de inyecciones de placebo a los niños. Dos estudios demostraron que el placebo no fue tan bueno como el tratamiento activo en la resolución de los espasmos. La evidencia más fuerte sugiere que el tratamiento hormonal (prednisolona o tetracosactida depot) conduce a la resolución de los espasmos más rápido y de más niños que hace vigabatrina. Respuestas sin recaída posterior pueden ser diferentes. El mismo estudio sugiere que los tratamientos hormonales podrían mejorar el resultado a largo plazo de desarrollo en comparación con vigabatrina en niños que no se encuentran para tener una causa subyacente de los espasmos infantiles.
Conclusiones de los revisores: Hasta la fecha, pocos ECA bien diseñados han considerado el tratamiento de los espasmos infantiles, y el número de pacientes incluidos han sido pequeños. En la mayoría, la metodología ha sido pobre, por lo tanto, no está claro que el tratamiento es óptimo en el tratamiento de este síndrome de la epilepsia. El tratamiento hormonal tiene espasmos en más niños que la vigabatrina, pero esto puede o no puede traducirse en mejores resultados a largo plazo. Si se utiliza prednisolona o vigabatrina, se recomienda alta dosificación. La vigabatrina puede ser el tratamiento de elección en la esclerosis tuberosa. Resolución de las características del EEG puede ser importante, pero esto no ha sido demostrado. Se requiere más investigación con estudios de gran tamaño con una metodología robusta.
To compare the efficacy and safety of prednisolone/prednisone and adrenocorticotropic hormone (ACTH) in the treatment of infantile spasms using a meta‐analysis of randomized controlled trials (RCTs).
METHOD:
In a systematic literature search of electronic databases (MEDLINE, Embase, the Cochrane Library), we identified RCTs that assessed prednisolone/prednisone compared with ACTH/tetracosactide in patients with infantile spasms. The electroclinical response and adverse events were evaluated.
RESULTS:
Six RCTs (616 participants) were included in the meta‐analysis. Compared with prednisolone/prednisone, ACTH/tetracosactide was not superior in terms of cessation of spasms at day 14 (relative risk 1.19, 95% confidence interval [CI] 0.74–1.92), day 42 (relative risk 1.02, 95% CI 0.63–1.65), and resolution of hypsarrhythmia on electroencephalogram (relative risk 1.14, 95% CI 0.71–1.81); the incidences of common adverse reactions caused by ACTH/tetracosactide were not lower than that of prednisolone/prednisone for irritability (relative risk 0.79, 95% CI 0.57–1.10), increased appetite (relative risk 0.78, 95% CI 0.57–1.08), weight gain (relative risk 0.86, 95% CI 0.56–1.32), and gastrointestinal upset (relative risk 0.60, 95% CI 0.35–1.02), though it seemed less frequent.
INTERPRETATION:
Prednisolone/prednisone elicits a similar electroclinical response as ACTH for infantile spasms, which indicates that it can be an alternative to ACTH for treating infantile spasms. What this paper adds Prednisolone/prednisone is as effective as adrenocorticotropic hormone (ACTH) in electroclinical response of infantile spasms. Prednisolone/prednisone and ACTH cause similar and tolerable adverse effects, whose incidences are comparable. High‐dose prednisone/prednisolone might be preferable to low dose for achieving freedom from spasms. (PsycInfo Database Record (c) 2020 APA, all rights reserved)
