In this study we set out to examine medication use in people with FXS and to determine community priorities for future clinical trials. We found that over half of respondents were already prescribed medication, these were predominantly SSRIs, stimulants, melatonin and antiepileptic drugs. There was a greater percentage of people prescribed medication in USA/Canada than in other countries with stimulant prescriptions primarily accounting for this. These results are similar to those from trials looking at other neurodevelopmental conditions showing that people in the USA/ Canada are more likely to be prescribed medication than those from other parts of the world (11, 12). Just under half of those not taking medicine highlighted that they would like to have access to medicines, particularly to help with anxiety and difficult behaviour, and 29% of participants reported not being able to access medicine due to an unwillingness from healthcare professionals to prescribe – notably all of these responses came from the UK. Common co-occurring mental disorders (e.g. anxiety and ADHD) should be considerd in FXS and treated where they exist (13), but the current study shows clear geographical variation in prescription habits, as well as a perceived difficulty in accessing medication in the UK. While some studies do exist (7–9) the development of an evidence base in regard to the efficacy of existing treatments in fragile X syndrome is required in order to guide clinicians and ensure that treatments are received or withheld appropriately.
With regard to trials, it was interesting to note that only half of respondents had heard about medication trials in FXS despite almost two thirds being interested in taking part in a trial of an already available medicine. There therefore appears to be a clear appetite within the FXS community for medication trials to take place and highlights the need for trials to be well advertised, so that those who would like to take part can be given the opportunity. The reasons for not wanting to take part in trials were mainly not being aware of any, travel, concern about coming off current medication and side effects, findings which are similar to previous studies carried out in this area (10, 14, 15)
Anxiety and ability to learn were the two most frequently endorsed priorities highlighted for targeting by future trials, with language, attention and social behaviour also highlighted by more than half of participants. It is interesting that two of these five priorities (anxiety and attention) are areas for which medications already exist but, as mentioned above, there is a lack of strong evidence for their use in fragile X syndrome (16). A search of clinicaltrials.gov for fragile X syndrome shows 58 registered treatment trials for medication (8 of which are currently ongoing) (17); of these none employed existing treatments to target either anxiety or attention, suggesting that this is an unconsidered area in fragile X. The other priorities (learning, language and social behaviour) are more usually regarded as ‘core’ features of fragile X and do tend to be addressed by the identified studies on clinicaltrials.gov (which are primarily of treatments targeted at the underlying pathophysiology of the condition).
In summary, this study demonstrates that medication use is common within the fragile X community and that there is an appetite for clinical trials, especially targeting anxiety and learning. Almost all recent medication trials are targeted at core features of the condition, suggesting that there is a need for more studies to guide clinicians around the effective use of existing treatments for associated features.
While there are responses from 10 countries worldwide, the results are still limited by a relatively small sample size. The survey was advertised via several routes, however there may be a degree of ascertainment bias, with those more actively engaged with FXS communities and thus more likely to see the adverts not being fully representative of the wider fragile X communities. We were unable to collect a representative sample of genders, which may have an impact on results as we know males with FXS are often more affected. The study did not specifically ask about side effects of medications - while side effects were not reported as a specific reason for not taking medications this would be interesting to study further.