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

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: , identifier NCT02385799.

Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis

“…We did not find an effect of trial duration, yet shorter-term trials have been associated with larger placebo response in psychiatry [ 50 ]. However, in longer-term trials including young children, anticipated developmental trajectories could also explain placebo effects and subsequently mask drug-placebo differences [ 101 ]. Therefore, developmentally based scales might be necessary to overcome this challenge [ 82 ] as well as trial designs could include additional follow-up assessments in order to confirm stability of improvement [ 101 ].…”

Molecular Biomarkers Predictive of Sertraline Treatment Response in Young Children With Autism Spectrum Disorder

“…The amount that was used at each 3 months visit was measured to document compliance. More details are described in Potter et al (2019). Biological samples collected at baseline and post-treatment were approved by the UC Davis Institutional Review Board.…”

“…Thus, evidence suggests that sertraline could be useful in young children with ASD since the serotonergic system is disrupted in early development of ASD children. Based on these findings, a 6-month randomized, placebo-controlled, doubleblind clinical trial of low-dose sertraline in children ages 39-71 months old with ASD was conducted at the UC Davis MIND Institute to evaluate the efficacy and benefit with respect to early expressive and receptive language development and global clinical improvement (Potter et al, 2019). In the present study, we further investigated the participants to identify molecular biomarkers predictive of efficacy and responsiveness to sertraline treatment in ASD.…”

Predictors of Anxiety in a Sample of Preschoolers with ASD

“…Ghanbari et al (2011) in their research on irainian children showed that ubscales of PAS had moderate to high internal consistency and good reliabiity. Validity evaluations also yielded positive results (29) The PAS has previously been employed and indicated to be a valid measure of anxiety levels in preschoolers with ASD (30,31). The score of obsessive-compulsive subscale was not included, because children with ASD serve this behavior for self-soothing or regulation of emotions (32) and it is not related to anxiety.…”

“…Another limitation is that lack of psychometric characteristics for the ASD preschoolers of the PAZ may lead to an unreliable evaluation of anxiety. However, this scale has previously been used to measure anxiety in preschoolers with ASD and indicated to be a valid measure of anxiety levels in this population (30,31).…”