A Randomized, Double-Blind, Placebo-Controlled Trial of Low-Dose Sertraline in Young Children With Fragile X Syndrome.

The trial was exploratory and smaller than planned: it required 60 participants but randomized 57, and 52 completed six months. Many secondary and post hoc analyses were performed, increasing the chance that a significant result is spurious. Children and caregivers were unblinded when they finished the study with their child, not at the end of the overall trial, which could bias parent and clinician ratings. Only nine girls were included, so possible differences between boys and girls could not be assessed. More than 93% of each group also received speech and language therapy and occupational therapy, and both groups had expected developmental gains over six months, so the contribution of sertraline cannot be separated from these therapies and normal development. Many standard scores were floored at the lowest score of 20, so the authors used post hoc age-equivalent scores, which changes the measure being reported. The positive ASD subgroup finding was post hoc, and the non-ASD subgroup was very small.

Do not read the significant fine motor, visual reception, combined MSEL, social participation, or ASD subgroup findings as proof that low-dose sertraline improves development in young children with fragile X. The three pre-specified primary outcomes were not significant, these other results were secondary or post hoc, and the children also received speech and language therapy and occupational therapy, so the contribution of sertraline cannot be separated.