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01-12-2022 | Attention Deficit Hyperactivity Disorder | Research

Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis

Authors: Spyridon Siafis, Oğulcan Çıray, Hui Wu, Johannes Schneider-Thoma, Irene Bighelli, Marc Krause, Alessandro Rodolico, Anna Ceraso, Giacomo Deste, Maximilian Huhn, David Fraguas, Antonia San José Cáceres, Dimitris Mavridis, Tony Charman, Declan G. Murphy, Mara Parellada, Celso Arango, Stefan Leucht

Published in: Molecular Autism | Issue 1/2022

Abstract

Background

There 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.

Methods

We 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.

Results

We 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.

Limitations

Most 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.

Conclusions

Some 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.

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Title: Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis
Authors: Spyridon Siafis
Oğulcan Çıray
Hui Wu
Johannes Schneider-Thoma
Irene Bighelli
Marc Krause
Alessandro Rodolico
Anna Ceraso
Giacomo Deste
Maximilian Huhn
David Fraguas
Antonia San José Cáceres
Dimitris Mavridis
Tony Charman
Declan G. Murphy
Mara Parellada
Celso Arango
Stefan Leucht
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Attention Deficit Hyperactivity Disorder
Autism Spectrum Disorder
Bumetanide
Attention Deficit Hyperactivity Disorder
Anxiety
Aripiprazole
Risperidone
Published in: Molecular Autism / Issue 1/2022
Electronic ISSN: 2040-2392
DOI: https://doi.org/10.1186/s13229-022-00488-4

2024 ASCO Annual Meeting

Springer Medicine

Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis

Abstract

Background

Methods

Results

Limitations

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Limitations

Conclusions

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