J020 Antidepressants are associated with slower clinical, imaging and fluid biomarkers of progression in Huntington’s disease

<h3>Background</h3> Antidepressants are frequently prescribed in HD. Previous studies have raised concern that antidepressants may be associated with more rapid disease progression in HD, but have not accounted for causality, and did not measure the effects of antidepressants on non-clinical biomarkers. <h3>Aims</h3> 1. Determine the commonest indications for antidepressant prescription in HD 2. Sample participants with common incident indications for antidepressants, and compare clinical disease progression between those starting antidepressants versus those not 3. Sample participants with common incident indications for antidepressants, and compare imaging and fluid biomarkers of disease progression between those starting antidepressants versus those not. <h3>Methods</h3> Leveraging data from ENROLL-HD and TRACK-HD, we first categorised the indication for antidepressant prescription into common psychiatric symptoms, then selected incident cases and used propensity scoring to account for baseline risk factors. We used linear mixed models to measure disease progression in ENROLL-HD and generalised linear models to compare change from baseline in TRACK-HD. <h3>Results</h3> Anxiety and depression accounted for &gt;80% of prescription indications. Antidepressant-naive, Incident cases of depression and anxiety, were selected for the analysis in ENROLL-HD and TRACK-HD. Participants starting an antidepressant before the next follow-up visit had slower deterioration in the composite disease score and the UHDRS motor score in ENROLL-HD. Participants in TRACK-HD starting an antidepressant before the next follow-up had smaller change in NfL, larger putamen volume at final follow-up and larger putamen:ICV ratio at final follow-up. <h3>Conclusions</h3> Antidepressants are associated with slower disease progression on clinical, imaging and fluid biomarkers.