Research on animal models of fragile X syndrome suggests that STX209, a γ-aminobutyric acid type B (GABA B ) agonist, might improve neurobehavioral function in affected patients. We evaluated whether STX209 improves behavioral symptoms of fragile X syndrome in a randomized, double-blind, placebo-controlled crossover study in 63 subjects (55 male), ages 6 to 39 years, with a full mutation in the FMR1 gene (>200 CGG triplet repeats). We found no difference from placebo on the primary endpoint, the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. In the other analyses specified in the protocol, improvement was seen on the visual analog scale ratings of parent-nominated problem behaviors, with positive trends on multiple global measures. Post hoc analysis with the ABC-Social Avoidance scale, a newly validated scale for the assessment of fragile X syndrome, showed a significant beneficial treatment effect in the full study population. A post hoc subgroup of 27 subjects with more severe social impairment showed improvements on the Vineland II-Socialization raw score, on the ABC-Social Avoidance scale, and on all global measures. STX209 was well tolerated, with 8% incidences of sedation and of headache as the most frequent side effects. In this exploratory study, STX209 did not show a benefit on irritability in fragile X syndrome. Nonetheless, our results suggest that GABA B agonists have potential to improve social function and behavior in patients with fragile X syndrome.

Objective Pediatric inflammatory bowel disease (IBD) is associated with high rates of depression. This study compared the efficacy of cognitive behavioral therapy (CBT) to supportive non-directive therapy (SNDT) in treating youth with comorbid IBD and depression. Method Depressed youth (51% female; ages 9–17 years; mean age 14.3 years) with Crohn’s disease (n=161) or ulcerative colitis (n=56) were randomly assigned to a 3-month course of CBT or SNDT. The primary outcome was comparative reduction in depressive symptom severity; secondary outcomes were depression remission, increase in depression response, and improved health-related adjustment and IBD activity. Results 178 participants (82%) completed the 3-month intervention. Both psychotherapies resulted in significant reductions in total Children’s Depression Rating Scale Revised score (37.3% for CBT and 31.9% for SNDT), but the difference between the two treatments was not significant (p=0.16). There were large pre-post effect sizes for each treatment (d=1.31 for CBT and d=1.30 for SNDT). Over 65% of youth had a complete remission of depression at 3 months with no difference between CBT and SNDT (67.8% and 63.2%, respectively). Compared to SNDT, CBT showed a greater reduction in IBD activity (p=0.04) but no greater improvement on the Clinical Global Assessment Scale (p=0.06) and health-related quality of life (the IMPACT-III scale) (p=0.07). Conclusion This is the first randomized controlled study to suggest improvements in depression severity, global functioning, quality of life, and disease activity in a physically ill pediatric cohort treated with psychotherapy. Clinical trial registration information—Reducing Depressive Symptoms in Physically Ill Youth; URL: http://clinicaltrials.gov/; NCT00534911.

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