Antidepressants and Slower Disease Progression in Huntington’s Disease

AbstractImportanceAntidepressants are the most frequently prescribed medication in Huntington’s disease; this study examines the effect of antidepressants on disease progression.ObjectivesDetermine the effects on disease progression (composite score, brain atrophy, neurofilament light chain) in Huntington’s disease of (1) psychiatric symptoms and (2) accounting for (1) antidepressant use.DesignComparison of disease progression between individuals taking antidepressants and non-users, matching for other characteristics via propensity scores.SettingGlobal observational cohort studies. Enroll-HD (recruitment 2012-present, annual follow-up) TRACK-HD (recruitment 2008-2013, annual follow-up for 36 months).ParticipantsAdult with genetically-confirmed repeat expansion for Huntington’s disease not on antidepressants at baseline visit.Exposures(1) An episode of psychiatric symptoms (depression or anxiety occurring after baseline: problem behaviours assessment score >4 or hospital anxiety and depression score >7) (2) antidepressant use (WHO ATC code N06A) following a new episode of psychiatric symptoms.Main Outcome(s) and Measure(s)The clinical outcome measure was the annual change in composite score of disease progression (two cognitive task scores, a functional score and the motor score, derived from the unified HD rating scale). Biomarker outcomes were change from baseline to 3-year follow-up in a) neurofilament light chain b) brain atrophy in caudate, putamen, whole brain, gray matter, white matter and ventricles.ResultsPsychiatric symptoms (3131/6166 Enroll-HD: respective age&sex 47.93(13.81) 56% female,47.37(14.5) 50% female; 115/165 TRACK-HD: age&sex 47.1(9.63) 55% female,48.82(11.6) 48% female) were associated with faster disease progression, increasing composite score decline from 0.38 to 0.58/year (95%CI 0.15,0.25;p=1.2×10-14) and increased rise in neurofilament light chain by 5.3pg/ml (95%CI 1.58,9.024;p=0.007). Antidepressant naive HD participants with new depression or anxiety who started antidepressants (Enroll-HD 194/1877; respective age&sex 52.13(11.77) 57% female, 49.91(13.62) 55% female, TRACK-HD 6/55; respective age&sex 46(3.02) 67% female, 47.22(10.17) 35% female) had reduced composite score decline from 0.89 to 0.53/yr (95%CI 0.13-0.6; p=0.002); a smaller increase of neurofilament light chain by 6.77pg/ml (95%CI 1.8-11.6; p=0.011) and reduced brain atrophy across multiple regions (caudate, putamen, whole brain, gray matter).Conclusions and RelevanceAntidepressant use is associated with slower disease progression in HD on both clinical measures and biomarkers of disease progression. This may have relevance to other neurodegenerative diseases.