TOPLINE:

Depression and anxiety in patients with Huntington disease (HD) were associated with an increased risk for HD progression and all-cause mortality, but antidepressant initiation was linked to a reduced risk for both outcomes, new research showed.

METHODOLOGY:

• Researchers analyzed data from ENROLL-HD, an ongoing worldwide observational study, and identified more than 6000 adults with HD who were antidepressant-naive and free of psychiatric symptoms, identified with the Problem Behaviors Assessment Hospital Anxiety and Depression Scale, at baseline.
• Incident episodes of depression or anxiety occurred in more than 3000 participants during the study.
• Among the 1877 patients who developed symptoms while still antidepressant naive, 10% (mean age, 52 years; 57% women) initiated antidepressants before the next follow-up and nearly 90%(mean age, 50 years; 55% women) did not.
• Outcomes included disease progression, as measured with a composite disease score that combined Stroop word reading task and symbol digit modality task scores, total functional capacity, and unified HD rating scale motor score. All-cause mortality and suicide were also assessed.

TAKEAWAY:

• Depression and anxiety accounted for more than 80% of antidepressant indications. Overall, the composite disease score deteriorated by 0.46 per year, with a single episode of psychiatric symptoms associated with an additional decline of 0.06 per year (P = 3.1 × 10^-¹¹).
• Psychiatric symptoms were also linked to increased risk for all-cause mortality (hazard ratio [HR], 1.5; P = 9.4 × 10^-⁶).
• In patients with new-onset psychiatric symptoms, antidepressant initiation was associated with slowed disease progression, with a reduced annual composite score from 0.89 to 0.53 points (P = .002), and reduced all-cause mortality (HR,.38; P = .04). Treated patients survived a mean of 1180.9 days compared with 700.8 days for the untreated patients.
• In an exploratory analysis, tricyclic antidepressants and atypical agents were linked to significantly reduced risk for all-cause mortality, selective serotonin reuptake inhibitors to reduced risk for only suicide, and serotonin noradrenaline reuptake inhibitors to reduced risk for only nonsuicide-related mortality.

IN PRACTICE:

“In this work, we have shown reduced mortality risk and slower disease progression on clinical, imaging biomarker, and fluid biomarkers in HD patients treated with antidepressants compared to untreated patients,” the investigators wrote.

“This finding may be of wider applicability to other neurodegenerative diseases and raises the possibility of a second mechanism contributing to disease progression in HD,” they added.

SOURCE:

This study was led by Duncan McLauchlan, PhD, School of Medicine, Cardiff University, Cardiff, Wales. It was published online on January 21 in Brain.

LIMITATIONS:

The study’s observational design could not account for unobserved confounders despite propensity score matching. The use of two different scales to assess depression and anxiety, with only moderate correlation, introduced uncertainty in symptom measurement. Additionally, the small sample sizes in some antidepressant class groups warranted cautious interpretation of class-specific mortality effects.

DISCLOSURES:

ENROLL-HD was funded by Cure Huntington’s Disease Initiative Foundation. Some investigators reported having financial or other ties with various organizations, which are fully listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.