A Randomized Controlled Trial of Sertraline in Young Children With Autism Spectrum Disorder.

Laura A Potter,Susan M Rivera,Akash Rajaratnam,Yanjun Chen,Danielle A Scholze,Randi J Hagerman,Reem R Al Olaby,Danh V Nguyen,Hazel Maridith B Biag,Flora Tassone,Patrick S Dwyer,Nimrah S Choudhary,Maria J Salcedo-Arellano,Andrea Schneider

doi:10.3389/fpsyt.2019.00810

Abstract

Objective: Selective serotonin reuptake inhibitors like sertraline have been shown in observational studies and anecdotal reports to improve language development in young children with fragile X syndrome (FXS). A previous controlled trial of sertraline in young children with FXS found significant improvement in expressive language development as measured by the Mullen Scales of Early Learning (MSEL) among those with comorbid autism spectrum disorder (ASD) in post hoc analysis, prompting the authors to probe whether sertraline is also indicated in nonsyndromic ASD. Methods: The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 58 children with ASD aged 24 to 72 months. Results: 179 subjects were screened for eligibility, and 58 were randomized to sertraline (32) or placebo (26). Eight subjects from the sertraline arm and five from the placebo arm discontinued. Intent-to-treat analysis showed no significant difference from placebo on the primary outcomes (MSEL expressive language raw score and age equivalent combined score) or secondary outcomes. Sertraline was well tolerated, with no difference in side effects between sertraline and placebo groups. No serious adverse events possibly related to study treatment occurred. Conclusion: This randomized controlled trial of sertraline treatment showed no benefit with respect to primary or secondary outcome measures. For the 6-month period, treatment in young children with ASD appears safe, although the long-term side effects of low-dose sertraline in early childhood are unknown. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02385799.

Highlights

Autism spectrum disorder (ASD) is a behaviorally defined developmental disorder characterized by deficits in social communication and interaction in conjunction with the presence of restricted, repetitive patterns of behavior [1]
The 58 participants were randomized to the sertraline arm (n = 32) or placebo arm (n = 26)
Case reports of children aged 6 to 12 years treated with lowdose fluoxetine cited rapid and significant improvement in selfinjurious behavior, hyperactivity, irritability, and impulsivity [36]

Summary

Introduction

Autism spectrum disorder (ASD) is a behaviorally defined developmental disorder characterized by deficits in social communication and interaction in conjunction with the presence of restricted, repetitive patterns of behavior [1]. ASD is understood to have many causes, including an estimated over 1,000 gene mutations that can lead to deficits in synaptic plasticity, neuronal migration, transcription and translation changes, and many other processes important for synapse development and central nervous system (CNS) connectivity [2]. Known specific causes accounting for more than 2 to 3% of all ASD cases include fragile X syndrome (FXS) and tuberous sclerosis, many more single gene mutations, duplications, or deletions can cause 1% or less of cases. In individuals with ASD compared to neurotypical controls, higher rates of putative functional de novo mutations are observed [1], and whole genome sequencing can identify genetic mutations in up to 30% of those with ASD [4]. As many as 50% of de novo mutations resulting in ASD appear to occur in genes regulated by or associated with FMRP, the protein lacking in patients with FXS due to methylation of the FMR1 gene on the X chromosome, suggesting a potential overlap in beneficial treatments between FXS and ASD [5]

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Results

Discussion

Conclusion