Intravenous secretin for autism spectrum disorders (ASD).
TL;DR: There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD.
Abstract: BACKGROUND: In 1998 secretin, a gastrointestinal hormone, was suggested as an effective treatment for autism spectrum disorders (ASD) based on anecdotal evidence. OBJECTIVES: To assess whether intravenous secretin improves the core features of ASD, other aspects of behaviour or function such as self-injurious behaviour, and the quality of life of affected individuals and their carers. We also assessed whether secretin causes harm. This is an updated version of our review of this topic originally published in 2005. SEARCH METHODS: We searched CENTRAL (2010 Issue 1), MEDLINE (1950 to January 2010) , EMBASE (1980 to 2010 Week 2), PsycINFO (1806 to 2010 Week 2), CINAHL (1938 to January 2010), ERIC (1966 to January 2010), Sociological Abstracts (1952 to January 2010). Sociofile and HealthStar were searched in March 2005 when this review was first published, but were not available for this update. Records were limited to studies published since 1998 as this is when secretin was first proposed as a possible treatment for ASD. We searched reference lists of trials and reviews; we also contacted experts and trialists to find unpublished studies. SELECTION CRITERIA: Randomised controlled trials of intravenous secretin compared to a placebo treatment in children or adults diagnosed with ASD, where at least one standardised outcome measure was reported. DATA COLLECTION AND ANALYSIS: Sixteen studies met the inclusion criteria but for two of these, conducted by Repligen, the only available multisite data were reported in press releases. All outcome data from the other 14 trials were continuous. Where trials used cross-over designs, we conducted analysis on results from the first treatment phase. Where mean change from baseline was reported, we used this in preference to post-treatment scores for meta-analyses or forest plots. Meta-analysis was able to be attempted for only one outcome (Childhood Autism Rating Scale). Insufficient data were available to conduct sensitivity or subgroup analyses to assess the impact of study quality, clinical differences in the intervention or clinically relevant differences between groups, such as age or presence of gastrointestinal symptoms. MAIN RESULTS: Over 900 children were recruited for the secretin trials. Twenty-five established standardised outcome measures were reported to assess core features of ASD, communication, behaviour, visuospatial skills, affect and adverse events. One standardised measure of global impression was also used. No more than four studies used any one outcome measure similarly. When duration from the start of the intervention to outcome assessment was known, outcomes were reported at between three and six weeks. Meta-analysis of data was not possible but there is now consistency of findings, with RCTs of the efficacy of secretin in autism not showing improvements for core features of ASD. AUTHORS' CONCLUSIONS: There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin's effectiveness for ASD can only be justified if there is new high-quality and replicated scientific evidence that either finds that secretin has a role in neurotransmission in a way that could benefit all children with ASD or identifies important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing.
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TL;DR: CHA use was negatively associated with older child age and positively associated with parents’ belief ASD has major consequences, living in Portland or Denver, and medication use, and study findings may have utility for healthcare providers working with children with ASD and their families regarding CHA.
Abstract: Knowledge of why parents use complementary health approaches (CHA) for children with autism spectrum disorder (ASD) is limited. We conducted a mixed methods study to better understand factors influencing parents' decision to use CHA for ASD. Parent-reported data about CHA use were collected on a probability sample of 352 young children with ASD in Denver, Colorado; Los Angeles, California; or Portland, Oregon. Follow-back interviews were conducted with 31 parents. CHA use was negatively associated with older child age and positively associated with parents' belief ASD has major consequences, living in Portland or Denver, and medication use. Nine themes help explain these results. Study findings may have utility for healthcare providers working with children with ASD and their families regarding CHA.
25 citations
TL;DR: Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders that manifest in early childhood and persist throughout the lifespan; treatment should reflect the unique challenges for that individual at each developmental stage.
Abstract: Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders that manifest in early childhood and persist throughout the lifespan; treatment should reflect the unique challenges for that individual at each developmental stage. In early childhood, treatment should focus on the acquisition of language, play skills, joint attention, and effective communication strategies through intensive behavioral and educational interventions, particularly Applied Behavioral Analysis (ABA). Middle childhood and adolescence presents a time for continued skills acquisition, including development of social skills, peer relationships, and maximizing supports for academic weaknesses. In older adolescence and young adulthood, developing vocational and adaptive living skills to maximize opportunities for independence becomes important. ASD are lifelong disorders, and treatment in adulthood includes ensuring opportunities for social, leisure, and vocational activities, maintaining physical health through diet and exercise, and support for transitions in caregiving as parents age. Throughout the lifespan, clinicians should remain mindful of medical complications that can affect behavior and may not be readily apparent in individuals with limited verbal abilities, including gastrointestinal problems such as reflux and constipation, seizures, and allergies. Current pharmacological interventions are primarily aimed at ameliorating the challenging emotional and behavioral symptoms that accompany ASD rather than the core symptoms of ASD themselves. However, substantial evidence-based research into most medications for ASD is lacking. Two atypical antipsychotics, risperidone and aripiprazole, have indication for the treatment of severe irritability in youths with ASD, though all other medication use in ASD is considered off-label. Behaviorally based therapies, including ABA and cognitive-behavioral therapy (CBT), may be helpful for symptoms of depression, anxiety, and impaired self-regulation. Clinicians should remain mindful that many families will seek out complementary and alternative medicine (CAM) approaches for their child, and appropriate guidance about the safety and efficacy of these interventions should be offered. Drug therapies that directly target the varied neurobiological underpinnings of ASD are an area of great interest for future research and treatment.
22 citations
28 Apr 2014-Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
TL;DR: The following etiological treatment are reviewed: acetylcholine and glutamate related medicine; amino acid medicine such as secretin, endogenous opioid, and oxytocin; complementary and alternative Medicine such as chelating agents, vitamins, and omega-3; promising drugs related to the scope of pharmacogenetics currently under study.
Abstract: In clinical practice, pharmacological treatment is mostly focused on behavioral symptoms in everyday life. Nevertheless, persistent effort continues to develop medication for causal treatment. Recent changes in diagnostic criteria from Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) to DSM-5 would affect not only diagnosing approaches, but also therapeutic approaches. Because previous pervasive developmental disorders have been integrated into a single entity, the autism spectrum disorder (ASD), we have to prepare for what medications are valuable for the ASD. In this article, we reviewed the following etiological treatment: acetylcholine and glutamate related medicine; amino acid medicine such as secretin, endogenous opioid, and oxytocin; complementary and alternative medicine such as chelating agents, vitamins, and omega-3; promising drugs related to the scope of pharmacogenetics currently under study.
21 citations
TL;DR: In this paper, the authors reviewed pathophysiological properties of OXT in whole body and effects of novel peptides such as AM family as well as other peptides on OXT release.
21 citations
Cites background from "Intravenous secretin for autism spe..."
...Although the treatment of secretin was eneficial in autism and associated gastrointestinal abnoralities [217], its efficacy was not confirmed in subsequent linical trials [218]....
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...Moreover, these studies have suggested n the existence of a specific relationship between autism nd inflammatory bowel disease [218]....
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...[218] K....
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TL;DR: Acupuncture, gluten and casein-free diets, early intensive behavioral interventions, music therapy, parent-mediated early interventions, social skill groups and the Theory of Mind cognitive model seem to have benefits for patients with autism spectrum disorders (very low to low-quality evidence).
Abstract: CONTEXTO E OBJETIVO: Os transtornos do espectro autista (TEA) incluem autismo, doenca de Asperger e transtorno global do desenvolvimento. As manifestacoes dos TEA podem ter importante impacto na aprendizagem e funcionamento social, que pode persistir durante a fase adulta. O objetivo foi resumir as evidencias de revisoes sistematicas Cochrane sobre intervencoes para TEA. TIPO DE ESTUDO E LOCAL: Revisao de revisoes sistematicas conduzida na Disciplina de Medicina Baseada em Evidencias da Escola Paulista de Medicina, Universidade Federal de Sao Paulo. METODOS: Nos incluimos e resumimos os resultados de revisoes sistematicas Cochrane sobre intervencoes para TEA. RESULTADOS: Foram incluidas 17 revisoes que encontraram evidencias fracas de beneficios da acupuntura, dietas isentas de gluten e caseina, intervencao comportamental intensiva precoce, musicoterapia, intervencao precoce mediada pelos pais, grupos de habilidades sociais, modelo cognitivo de Teoria da Mente, aripiprazol, risperidona, antidepressivos triciclicos, inibidores seletivos da recaptacao da serotonina (ISRS); o ultimo apenas para adultos. Nenhum beneficio foi encontrado com terapias sonoras, agentes quelantes, oxigenoterapia hiperbarica, omega-3, secretina, vitamina B6/magnesio e ISRS para criancas. CONCLUSAO: Acupuntura, dietas sem gluten e caseina, intervencao comportamental intensiva precoce, musicoterapia, intervencao precoce mediada pelos pais, grupos de habilidades sociais e modelo cognitivo de Teoria da Mente parecem ter beneficios para pacientes com TEA (evidencia de qualidade muito baixa a baixa). Aripiprazol, risperidona, antidepressivos triciclicos e ISRS (o ultimo apenas para adultos) tambem apresentam algum beneficio, embora estejam associados a maior risco de eventos adversos. Estudos experimentais confirmando a relacao entre provaveis terapias e a doenca, e entao ensaios clinicos de alta qualidade e de longo seguimento, sao necessarios.
20 citations
References
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TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure
37,989 citations
TL;DR: It is concluded that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity, and one or both should be presented in publishedMeta-an analyses in preference to the test for heterogeneity.
Abstract: The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity.
25,460 citations
Book•
23 Sep 2019TL;DR: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.
Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.
21,235 citations
Book•
01 Jun 1991
12,618 citations
"Intravenous secretin for autism spe..." refers background in this paper
...Behaviour scales (for example, the Child Behavior Checklist (Achenbach 1991)) 5....
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