Equity, acceptability and feasibility of using polyunsaturated fatty acids in children and adolescents with autism spectrum disorder: a rapid systematic review

Health Qual Life Outcomes

Amato³

et al. 2021

Self Cite

Background The net health benefit of using antipsychotics in children and adolescents with ASD is unclear. This review was performed to provide the evidence necessary to inform the Italian national guidelines for the management of ASD. Methods We performed a systematic review of randomized controlled trials (RCTs) comparing antipsychotics versus placebo for the treatment of ASD in children and adolescents. For efficacy, acceptability and safety we considered outcomes evaluated by the guideline panel critical and important for decision-making. Continuous outcomes were analyzed by using standardized mean difference (SMD), and dichotomous outcomes by calculating the risk ratio (RR), with their 95% confidence interval (95% CI). Data were analyzed using a random effects model. We used the Cochrane tool to assess risk of bias of included studies. Certainty in the evidence of effects was assessed according to the GRADE approach. Results We included 21 RCTs with 1,309 participants, comparing antipsychotics to placebo. Antipsychotics were found effective on “restricted and repetitive interests and behaviors” (SMD − 0.21, 95% CI − 0.35 to − 0.07, moderate certainty), “hyperactivity, inattention, oppositional, disruptive behavior” (SMD − 0.67, 95% CI − 0.92 to − 0.42, moderate certainty), “social communication, social interaction” (SMD − 0.38, 95% CI − 0.59 to − 0.16, moderate certainty), “emotional dysregulation/irritability” (SMD − 0.71, 95% CI − 0.98 to − 0.43, low certainty), “global functioning, global improvement” (SMD − 0.64, 95% CI − 0.96 to − 0.33, low certainty), “obsessions, compulsions” (SMD − 0.30, 95% CI − 0.55 to − 0.06, moderate certainty). Antipsychotics were not effective on “self-harm” (SMD − 0.14, 95% CI − 0.58 to 0.30, very low certainty), “anxiety” (SMD − 0.38, 95% CI − 0.82 to 0.07, very low certainty). Antipsychotics were more acceptable in terms of dropout due to any cause (RR 0.61, 95% CI 0.48 to 0.78, moderate certainty), but were less safe in terms of patients experiencing adverse events (RR 1.19, 95% CI 1.07 to 1.32, moderate certainty), and serious adverse events (RR 1.07, 95% CI 0.48 to 2.43, low certainty). Conclusions Our systematic review and meta-analysis found antipsychotics for children and adolescents with ASD more efficacious than placebo in reducing stereotypies, hyperactivity, irritability and obsessions, compulsions, and in increasing social communication and global functioning. Antipsychotics were also found to be more acceptable, but less safe than placebo.

Section: Study Limitationsmentioning

confidence: 99%

Impact of antipsychotics in children and adolescents with autism spectrum disorder: a systematic review and meta-analysis

D’Alò¹,

Health Qual Life Outcomes

Amato³

et al. 2021

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“…Although the efficacy of PUFAs in children and adolescents with ASD is still controversial, PUFAs are administered to a portion of this population ranging from 18 to 51% [67,68], probably thanks to the fact that costs and difficulties of implementation appear negligible [69], and safety concerns seem small [65]. Also the rationale behind the administration of PUFAs in individuals with ASD, i.e.…”

Section: Discussionmentioning

confidence: 99%

Impact of polyunsaturated fatty acids on patient-important outcomes in children and adolescents with autism spectrum disorder: a systematic review

Health Qual Life Outcomes

D’Alò

Morgano

et al. 2020

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Background: Recent randomized controlled trials (RCTs) claimed PUFAs to be effective for autism spectrum disorder (ASD) but international guidelines have not considered yet this body of evidence. Our aim was to assess the effectiveness of PUFAs in children and adolescents with ASD, for the Italian national guidelines on the management of ASD in children and adolescents. Methods: We performed a systematic review and meta-analysis of RCTs comparing PUFAs versus placebo or a healthy diet for the treatment of ASD in children and adolescents. The outcomes considered were deemed by the guideline panel to be highly relevant to children and adolescents with ASD and to their caregivers. The outcomes included hyperactivity, quality of sleep, self-harm, aggression, irritability, anxiety, attention, adaptive functioning, social interaction, restricted and repetitive interests and behavior, communication, hyperactivity and disruptive behaviors coexistent with core symptoms. The risk of bias of the included studies was assessed with the Cochrane tool, and the rating of the confidence in the effect estimates according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: We included 9 studies with 405 participants. The strength of evidence ranged from low to very low. Six studies included preschoolers and school-age children, three studies included both children and adolescents. The majority of participants were males (83.8%), with a mean age of 6.7 years. PUFAs were superior compared to placebo in reducing anxiety in individuals with ASD (SMD-1.01, 95% CI − 1.86 to − 0.17; very low certainty of evidence). Moreover, PUFAs worsened quality of sleep compared to a healthy diet (SMD 1.11, 95% CI 0.21 to 2.00; very low certainty of evidence). PUFAs were not better than placebo in reducing aggression, hyperactivity, adaptive functioning, irritability, restricted and repetitive interests and behaviors and communication. Effects on some critical outcomes such as sleep, self-harm and disruptive behavior are currently unknown. The main limitations were the small number of participants included in the RCTs and the dosage which varied greatly (from 200 mg/day to 1540 mg/day), making it difficult to address causal inference.

“…The use of the EtD framework in general, and the evaluation of its domains relating to equity, acceptability and feasibility, requires the panel to be familiar with the tool [ 63 ], and this is a potential limitation for the process of developing recommendations. To overcome this potential limitation, about 2 months before the presentation of the body of evidence on antipsychotics, an EtD framework on a pilot question was presented to the panel [ 64 , 65 ]. In other experiences, panel members have reported that, when familiarity with the EtD framework is achieved, the tool helped them in structuring discussion, saving time, ensuring systematicity in the process of recommendation formulation [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Acceptability, equity, and feasibility of using antipsychotics in children and adolescents with autism spectrum disorder: a systematic review

D’Alò¹,

Amato³

et al. 2020

BMC Psychiatry

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Background It is unclear whether the administration of antipsychotics to children and adolescents with autism spectrum disorders (ASD) is acceptable, equitable, and feasible. Methods We performed a systematic review to support a multidisciplinary panel in formulating a recommendation on antipsychotics, for the development of the Italian national guidelines for the management of ASD. A comprehensive search strategy was performed to find data related to intervention acceptability, health equity, and implementation feasibility. We used quantitative data from randomized controlled trials to perform a meta-analysis assessing the acceptability and tolerability of antipsychotics, and we estimated the certainty of the effect according to the GRADE approach. We extracted data from systematic reviews, primary studies, and grey literature, and we assessed the risk of bias and methodological quality of the published studies. Results Antipsychotics were acceptable (dropouts due to any cause: RR 0.61, 95% CI 0.48–0.78, moderate certainty of evidence) and well tolerated (dropouts due to adverse events: RR 0.99, 95% CI 0.55–1.79, low certainty of evidence) by children and adolescents with ASD. Parents and clinicians did not raise significant issues concerning acceptability. We did not find studies reporting evidence of reduced equity for antipsychotics in disadvantaged subgroups of children and adolescents with ASD. Workloads, cost barriers, and inadequate monitoring of metabolic adverse events were indirect evidence of concerns for feasibility. Conclusion Antipsychotics in children and adolescents with ASD were likely acceptable and possibly feasible. We did not find evidence of concern for equity.