Exploring the association between antidepressants, progression and mortality in Huntington's disease

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• Psychiatric symptoms are prevalent in Huntington's disease (HD), a neurodegenerative disorder.
• Concerns exist that antidepressants might accelerate disease progression in neurodegenerative conditions.
• Previous research in HD has been limited by methodological challenges.

Purpose of the Study:

• To investigate if symptoms prompting antidepressant use in HD are linked to faster disease progression.
• To determine the impact of antidepressants on disease progression and mortality in people with HD (pwHD).

Main Methods:

• Utilized data from the ENROLL-HD cohort (25,550 participants).
• Analyzed associations between antidepressant indication symptoms and disease progression/mortality using linear mixed models.
• Employed propensity score weighting to compare pwHD initiating antidepressants versus those remaining naive during symptom episodes.

Main Results:

• Depression and anxiety were the primary indications (>80%) for antidepressant prescriptions in pwHD.
• Episodes of depression/anxiety correlated with accelerated composite disease score progression and increased mortality.
• Antidepressant initiation in pwHD with new depression/anxiety significantly slowed disease progression and reduced all-cause mortality.

Conclusions:

• Depression and anxiety are associated with more rapid disease progression and higher mortality in HD.
• Antidepressant treatment in pwHD experiencing depression/anxiety slows disease progression and lowers mortality risk.
• Exploratory analysis suggests potential class-specific benefits of antidepressants on mortality in HD.