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 We searched reference lists of trials and reviews; we also contacted experts and trialists to find unpublished studies.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: There is no evidence to support the use of SSRIs to treat autism in children and emerging evidence of harm, and limited evidence of the effectiveness ofSSRIs in adults from small studies in which risk of bias is unclear.
Abstract: Background
Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of co-morbidity associated with ASD such as depression, anxiety and obsessive-compulsive behaviours.
Objectives
To determine if treatment with an SSRI:
1. improves the core features of autism (social interaction, communication and behavioural problems);
2. improves other non-core aspects of behaviour or function such as self-injurious behaviour;
3. improves the quality of life of children and their carers;
4. has short and long term effects on outcome;
5. causes harms.
Search strategy
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 4), MEDLINE ( December 2009), EMBASE (December 2009), CINAHL (December 2009), PsycINFO (December 2009) and ERIC (December 2009), without language restrictions.
Selection criteria
Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in participants with autism spectrum disorders. Trials must have included at least one standardised outcome measure.
Data collection and analysis
Two authors independently selected and appraised studies for inclusion and risk of bias. All data were continuous. Meta-analysis, where possible, used a random-effects model.
Main results
Seven RCTs with a total of 271 participants were included. Four SSRIs were evaluated: fluoxetine (two studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (one study). Five studies included only children and two studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence of participants. Seventeen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis. One large, high quality study in children showed no evidence of positive effect of citalopram. Two small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression, and another in anxiety.
Authors' conclusions
There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.
Plain Language Summary
Selective serotonin reuptake inhibitors for the treatment of autism spectrum disorders
Autism spectrum disorders (ASD) are characterised by problems with social interaction and communication, as well as repetitive behaviours and limited activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants which are sometimes given to help anxiety or obsessive compulsive behaviours. We found seven trials which evaluated four SSRIs: fluoxetine, fluvoxamine, fenfluramine and citalopram. Five studies included only children and two studies included only adults. One trial enrolled 149 children, but all other trials were small. We found no trials which evaluated sertraline, paroxetine or escitalopram. There is no evidence to support the use of SSRIs to treat autism in children. There is limited evidence, which is not yet sufficiently robust, to suggest effectiveness of SSRIs in adults with autism. Treatment with an SSRI may cause side effects. Decisions about the use of SSRIs for established clinical indications that may co-occur with autism, such as obsessive compulsive disorder and depression in adults or children, and anxiety in adults, should be made on a case by case basis.
15 citations
TL;DR: There is a paucity of systemic, well-conducted trials on the use of pharmacological agents in the management of PDD, and more research in this area is warranted.
Abstract: Objective: Pervasive developmental disorder (PDD) is associated with emotional and behavioural problems. There is no pharmacological cure for PDD, but some comorbidities and dysfunctional behaviours in PDD can be managed pharmacologically. The aim of the present study was to provide a better understanding of the efficacy and limitations in the currently available agents.Methods: Electronic literature searches were conducted from the following sources: MEDLINE, Cochrane Library, PSYARTICLES and PsycINFO. Search terms included, but were not limited to, ‘autism’, ‘PDD’, ‘autism spectrum disorder’ (‘ASD’), and ‘pharmacological management’.Results: A range of pharmacological agents are available for the management of various dysfunctional symptoms in PDD. Broadly speaking, these agents help in the management of repetitive stereotyped behaviours, anxiety, aggression/irritability/self-injurious behaviour, hyperactivity/inattention and in sleep.Conclusions: There is a paucity of systemic, well-conducted trials on...
14 citations
Journal Article•
TL;DR: The purpose of this systematic review is to summarize the most relevant historical, diagnostic and therapeutic aspects of ASD.
Abstract: Autism spectrum disorder (ASD) was described for the first time in 1943 by Leo Kanner, and since 2004, 18 490 articles in the subject have been published, which in turn have been cited 48 416 times.1 Almost half of these publications come from the United States of America and the vast maority of the efforts to improve the quality of life of these patients have taken place in developed countries. This disorder consists of an inability to acquire social and emotional skills during early development that progressively results in variable degrees of social adaptation discapacity. The etiology is multifactorial and includes functional and structural neurological abnormalities, some of them with putative genetic and/or epigenetic origin. There is an alarming lack of knowledge in the subject among health care professionals. The purpose of this systematic review is to summarize the most relevant historical, diagnostic and therapeutic aspects of ASD.
14 citations
TL;DR: Dietary manipulation may offer a cheap and easily implemented approach to improve the lives of those with ASD because a few approaches, such as the gluten-free/casein-free diet, fatty acid supplementation, and pre/probiotics have generally demonstrated improved GI and associated behavioral symptoms.
Abstract: This chapter reviews the literature surrounding autism spectrum disorders (ASD) and their relation to gastrointestinal (GI), behavioral, neurological, and immunological functioning. Individuals with ASD often have poor GI health, including bowel motility issues, autoimmune and/or other adverse responses to certain foods, and lack of necessary nutrient absorption. These issues may be caused or exacerbated by restrictive behavioral patterns (e.g., preference for sweet and salty foods and/or refusal of healthy foods). Those individuals with GI issues tend to demonstrate more behavioral deficits (e.g., irritability, agitation, hyperactivity) and also tend to have an imbalance in overall gut microbiome composition, thus corroborating several studies that have implicated brain–gut pathways as potential mediators of behavioral dysfunction.
14 citations
01 Jan 2011
TL;DR: This chapter discusses commonly used CAM therapies, reports the prevalence for use in children, reviews the factors promoting its use, and discusses the evidence-based evaluation of efficacy of treatments.
Abstract: Few treatments for autism generate as much controversy and consternation among families and caregivers than the group of treatments considered as complementary and alternative medical (CAM) treatments. Evidence-based practice should guide all treatments used for symptoms of autism, including behavioral, educational, medical biologic or complementary therapies. All interventions should be held to the same standards of evidence. This chapter discusses commonly used CAM therapies, reports the prevalence for use in children, reviews the factors promoting its use, and discusses the evidence-based evaluation of efficacy of treatments.
14 citations
Cites background from "Intravenous secretin for autism spe..."
...Prescription medications which have been the subject of offlabel use include secretin (Williams et al. 2005), vancomycin (Sandler et al....
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...Rv Williams et al. (2005) 14 studies; MA RCTs have not shown improvements for core features of autism...
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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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