Behavioural difficulties in fragile X syndrome: current pharmacological options and potential future developments

Fragile X Syndrome (FXS) is the most frequent inherited form of intellectual disability and a common cause of autism spectrum disorders and other neurodevelopmental conditions. It is commonly associated with hyperarousal, anxiety, and behavioral difficulties such as agitation, self-injurious behavior, and aggression.

This narrative review covers the physical, cognitive, and behavioral phenotype associated with FXS and the evidence for pharmacological interventions for behavioral difficulties, including those prescribed on the basis of symptoms and those aimed at the pathophysiological mechanisms of FXS ('targeted' interventions). Consideration is then given to the evidence for novel targeted treatments currently in later stages of clinical development.

The first-line management of behavioral difficulties are non-pharmacological interventions, and there are only a few studies in FXS to guide pharmacological approaches. Identification and management of anxiety and ADHD, which contribute to behavioral difficulties, are important steps before considering antipsychotic treatment for agitation, aggression, or self-injurious behavior. The evidence for repurposed targeted treatments remains based on small RCTs or open-label studies; therapeutic trials of these interventions therefore need close monitoring. Multiple novel medications are in clinical development; genetic therapies remain preclinical but are likely to be important in the coming years.