Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis / Spyridon SIAFIS in Molecular Autism, 13 (2022)  

Public ISBD [article]  inMolecular Autism > 13 (2022) . - 10 p. Titre : Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis Type de document : Texte imprimé et/ou numérique Auteurs : Spyridon SIAFIS, Auteur ; O?ulcan ÇIRAY, Auteur ; Hui WU, Auteur ; Johannes SCHNEIDER-THOMA, Auteur ; Irene BIGHELLI, Auteur ; Marc KRAUSE, Auteur ; Alessandro RODOLICO, Auteur ; Anna CERASO, Auteur ; Giacomo DESTE, Auteur ; Maximilian HUHN, Auteur ; David FRAGUAS, Auteur ; Antonia SAN JOSE CACERES, Auteur ; Dimitris MAVRIDIS, Auteur ; Tony CHARMAN, Auteur ; Declan G. MURPHY, Auteur ; Mara PARELLADA, Auteur ; Celso ARANGO, Auteur ; Stefan LEUCHT, Auteur Article en page(s) : 10 p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Attention Deficit Disorder with Hyperactivity  Autism Spectrum Disorder/drug therapy  Child  Humans  Network Meta-Analysis  Oxytocin/therapeutic use  Risperidone/therapeutic use  Adhd  Anxiety  Autism  Caregiver stress  Irritability  Meta-analysis  Response  Restricted and repetitive behaviors  Social communication  Treatment Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1186/s13229-022-00488-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 [article] Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis [Texte imprimé et/ou numérique] / Spyridon SIAFIS, Auteur ; O?ulcan ÇIRAY, Auteur ; Hui WU, Auteur ; Johannes SCHNEIDER-THOMA, Auteur ; Irene BIGHELLI, Auteur ; Marc KRAUSE, Auteur ; Alessandro RODOLICO, Auteur ; Anna CERASO, Auteur ; Giacomo DESTE, Auteur ; Maximilian HUHN, Auteur ; David FRAGUAS, Auteur ; Antonia SAN JOSE CACERES, Auteur ; Dimitris MAVRIDIS, Auteur ; Tony CHARMAN, Auteur ; Declan G. MURPHY, Auteur ; Mara PARELLADA, Auteur ; Celso ARANGO, Auteur ; Stefan LEUCHT, Auteur . - 10 p. Langues : Anglais (eng) in Molecular Autism > 13 (2022) . - 10 p. Mots-clés : Adolescent  Adult  Attention Deficit Disorder with Hyperactivity  Autism Spectrum Disorder/drug therapy  Child  Humans  Network Meta-Analysis  Oxytocin/therapeutic use  Risperidone/therapeutic use  Adhd  Anxiety  Autism  Caregiver stress  Irritability  Meta-analysis  Response  Restricted and repetitive behaviors  Social communication  Treatment Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1186/s13229-022-00488-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477

Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis / Spyridon SIAFIS in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 66 p. Titre : Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis Type de document : Texte imprimé et/ou numérique Auteurs : Spyridon SIAFIS, Auteur ; O?ulcan ÇIRAY, Auteur ; Johannes SCHNEIDER-THOMA, Auteur ; Irene BIGHELLI, Auteur ; Marc KRAUSE, Auteur ; Alessandro RODOLICO, Auteur ; Anna CERASO, Auteur ; Giacomo DESTE, Auteur ; Maximilian HUHN, Auteur ; David FRAGUAS, Auteur ; Dimitris MAVRIDIS, Auteur ; Tony CHARMAN, Auteur ; Declan G. MURPHY, Auteur ; Mara PARELLADA, Auteur ; Celso ARANGO, Auteur ; Stefan LEUCHT, Auteur Article en page(s) : 66 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Placebo  Trials  and/or for lectures from LB Pharma, Otsuka, Lundbeck, Boehringer Ingelheim, LTS  Lohmann, Janssen, Johnson&Johnson, TEVA, MSD, Sandoz, SanofiAventis, Angelini,  Recordati, Sunovion, and Geodon Richter. David Fraguas has been a consultant and/or  has received fees from Angelini, Eisai, IE4Lab, Janssen, Lundbeck, and Otsuka. He  has also received grant support from Instituto de Salud Carlos III (Spanish Ministry  of Science, Innovation and Universities) and from Fundación Alicia Koplowitz. Mara  Parellada has received educational honoraria from Otsuka, research grants from FAK  and Fundación Mutua Madrileña (FMM), Instituto de Salud Carlos III (Spanish Ministry  of Science, Innovation and Universities) and European ERANET and H2020 calls, travel  grants from Otsuka and Janssen. Consultant for Exeltis and Servier. Celso Arango has  been a consultant to or has received honoraria or grants from Acadia, Angelini,  Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, Roche, Sage, Sanofi, Servier,  Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. In the last  3 years, Maximilian Huhn has received speakers honoraria from Janssen. Declan Murphy  has received consulting fees from Roche. The other authors have nothing to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Placebo 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. METHODS: We 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 . RESULTS: Eighty-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. LIMITATIONS: About 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. CONCLUSIONS: Placebo 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. En ligne : http://dx.doi.org/10.1186/s13229-020-00372-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433 [article] Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis [Texte imprimé et/ou numérique] / Spyridon SIAFIS, Auteur ; O?ulcan ÇIRAY, Auteur ; Johannes SCHNEIDER-THOMA, Auteur ; Irene BIGHELLI, Auteur ; Marc KRAUSE, Auteur ; Alessandro RODOLICO, Auteur ; Anna CERASO, Auteur ; Giacomo DESTE, Auteur ; Maximilian HUHN, Auteur ; David FRAGUAS, Auteur ; Dimitris MAVRIDIS, Auteur ; Tony CHARMAN, Auteur ; Declan G. MURPHY, Auteur ; Mara PARELLADA, Auteur ; Celso ARANGO, Auteur ; Stefan LEUCHT, Auteur . - 66 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 66 p. Mots-clés : Autism spectrum disorder  Placebo  Trials  and/or for lectures from LB Pharma, Otsuka, Lundbeck, Boehringer Ingelheim, LTS  Lohmann, Janssen, Johnson&Johnson, TEVA, MSD, Sandoz, SanofiAventis, Angelini,  Recordati, Sunovion, and Geodon Richter. David Fraguas has been a consultant and/or  has received fees from Angelini, Eisai, IE4Lab, Janssen, Lundbeck, and Otsuka. He  has also received grant support from Instituto de Salud Carlos III (Spanish Ministry  of Science, Innovation and Universities) and from Fundación Alicia Koplowitz. Mara  Parellada has received educational honoraria from Otsuka, research grants from FAK  and Fundación Mutua Madrileña (FMM), Instituto de Salud Carlos III (Spanish Ministry  of Science, Innovation and Universities) and European ERANET and H2020 calls, travel  grants from Otsuka and Janssen. Consultant for Exeltis and Servier. Celso Arango has  been a consultant to or has received honoraria or grants from Acadia, Angelini,  Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, Roche, Sage, Sanofi, Servier,  Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. In the last  3 years, Maximilian Huhn has received speakers honoraria from Janssen. Declan Murphy  has received consulting fees from Roche. The other authors have nothing to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Placebo 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. METHODS: We 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 . RESULTS: Eighty-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. LIMITATIONS: About 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. CONCLUSIONS: Placebo 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. En ligne : http://dx.doi.org/10.1186/s13229-020-00372-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433

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