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Dietary Supplement for Core Symptoms of Autism Spectrum Disorder: Where Are We Now and Where Should We Go?

ABSTRACT: Autism spectrum disorders (ASDs) are a class of severe and chronic conditions and core symptoms are deficits in social interaction, language communication impairments, and repetitive/stereotyped behavior. Given the limitations of available treatments and substantially increased prevalence of the disease, additional interventions are needed. Since the use of dietary supplements for ASD is of high prevalence, up-to-date information about those supplements are required for both parents and clinicians. Relevant articles were identified through a systematic search of PubMed, EMBASE, Cochrane library, and PsychINFO databases (through May 2017). Current best evidences of 22 randomized controlled trials on 8 different dietary supplements for core symptoms of ASD were reviewed. For each supplement, this report focuses on the definition and potential therapeutic mechanisms, the latest advances, and discussion of study limitations and future directions. Most studies were small and short term, and there is little evidence to support effectiveness of dietary supplements for children with ASD.

SUBMITTER: Li YJ

PROVIDER: S-EPMC5572332 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Dietary Supplement for Core Symptoms of Autism Spectrum Disorder: Where Are We Now and Where Should We Go?

Li Yong-Jiang YJ Ou Jian-Jun JJ Li Ya-Min YM Xiang Da-Xiong DX

Frontiers in psychiatry 20170823

Autism spectrum disorders (ASDs) are a class of severe and chronic conditions and core symptoms are deficits in social interaction, language communication impairments, and repetitive/stereotyped behavior. Given the limitations of available treatments and substantially increased prevalence of the disease, additional interventions are needed. Since the use of dietary supplements for ASD is of high prevalence, up-to-date information about those supplements are required for both parents and clinicia ...[more]

PMID: 28878697

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Project description:BackgroundThere is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD.MethodsWe searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses.ResultsWe analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles.LimitationsMost of the studies were inadequately powered (sample sizes of 20-80 participants), with short duration (8-13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms.ConclusionsSome medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317.

Project description:BackgroundPlacebo response in autism spectrum disorder (ASD) might dilute drug-placebo differences and hinder drug development. Therefore, this meta-analysis investigated placebo response in core symptoms.MethodsWe searched ClinicalTrials.gov , CENTRAL, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (up to July 8, 2018), and PubMed (up to July 4, 2019) for randomized pharmacological and dietary supplement placebo-controlled trials (RCTs) with a minimum of seven days of treatment. Single-group meta-analyses were conducted using a random-effects model. Standardized mean changes (SMC) of core symptoms in placebo arms were the primary outcomes and placebo positive response rates were a secondary outcome. Predictors of placebo response were investigated with meta-regression analyses. The protocol was registered with PROSPERO ID CRD42019125317 .ResultsEighty-six RCTs with 2360 participants on placebo were included in our analysis (87% in children/adolescents). The majority of trials were small, single-center with a duration of 8-12 weeks and published after 2009. Placebo response in social-communication difficulties was SMC = - 0.32, 95% CI [- 0.39, - 0.25], in repetitive behaviors - 0.23[- 0.32, - 0.15] and in scales measuring overall core symptoms - 0.36 [- 0.46, - 0.26]. Overall, 19%, 95% CI [16-22%] of participants were at least much improved with placebo. Caregiver (vs. clinician) ratings, lower risk of bias, flexible-dosing, larger sample sizes and number of sites, less recent publication year, baseline levels of irritability, and the use of a threshold of core symptoms at inclusion were associated with larger placebo response in at least a core symptom domain.LimitationsAbout 40% of the trials had an apparent focus on core symptoms. Investigation of the differential impact of predictors on placebo and drug response was impeded by the use of diverse experimental interventions with essentially different mechanisms of action. An individual-participant-data meta-analysis could allow for a more fine-grained analysis and provide more informative answers.ConclusionsPlacebo response in ASD was substantial and predicted by design- and participant-related factors, which could inform the design of future trials in order to improve the detection of efficacy in core symptoms. Potential solutions could be the minimization and careful selection of study sites as well as rigorous participant enrollment and the use of measurements of change not solely dependent on caregivers.

Dataset Information

Dietary Supplement for Core Symptoms of Autism Spectrum Disorder: Where Are We Now and Where Should We Go?

Publications

Dietary Supplement for Core Symptoms of Autism Spectrum Disorder: Where Are We Now and Where Should We Go?

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