Antidepressants and Slower Disease Progression in Huntington’s Disease
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Abstract
Importance Antidepressants are the most frequently prescribed medication in Huntington’s disease; this study examines the effect of antidepressants on disease progression. Objectives Determine 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. Design Comparison of disease progression between individuals taking antidepressants and non-users, matching for other characteristics via propensity scores. Setting Global observational cohort studies. Enroll-HD (recruitment 2012-present, annual follow-up) TRACK-HD (recruitment 2008-2013, annual follow-up for 36 months). Participants Adult 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. Results Psychiatric 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 Relevance Antidepressant 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.
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Abstract
Importance Antidepressants are the most frequently prescribed medication in Huntington’s disease; this study examines the effect of antidepressants on disease progression.
Objectives
Determine 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.
Design Comparison of disease progression between individuals taking antidepressants and non-users, matching for other characteristics via propensity scores.
Setting Global observational cohort studies. Enroll-HD (recruitment 2012-present, annual follow-up) TRACK-HD (recruitment 2008-2013, annual follow-up for 36 months).
Participants Adult 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.
Results
Psychiatric 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 Relevance Antidepressant 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.
Competing Interest Statement
Acknowledgements
and Conflict of Interest Financial: Dr Drew has received financial honoraria for reviewing clinical trial protocols as part of the Enroll-HD clinical trials committee, Professor Holmans is paid an honorarium of $2000 per annum as part of the scientific review committee for Enroll-HD. Leadership: Dr McLauchlan is the chair of the SBAC committee of the EHDN a grant awarding body, Professor Holmans is a member of the SBAC. Professor Rosser is the previous President of the EHDN. Funding ENROLL-HD and TRACK-HD were funded by CHDI Foundation. Dr McLauchlan is funded by a Health and Care Research Wales Research Time award. Cheney Drew is funded by Health Care Research Wales, Michael J Fox Foundation and Jacques and Gloria Gossweiler Foundation. All other authors are funded by Cardiff University.
Funding Statement
ENROLL-HD and TRACK-HD were funded by CHDI Foundation. Dr McLauchlan is funded by a Health and Care Research Wales Research Time award. Cheney Drew is funded by Health Care Research Wales, Michael J Fox Foundation and Jacques and Gloria Gossweiler Foundation. All other authors are funded by Cardiff University.
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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
NHS Research Ethics Committee of Wales gave approval of this work (13/WA/0192)
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Data Availability
All data produced in the present study are available upon reasonable request to the authors
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