Title: Antidepressants in Huntington’s Disease: A Meta Analysis of Mood and Motor Outcomes with Placebo-controlled Trials
Authors: Jorge Patino, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, Andrew McGarry, Ian Walker, N. Rocha, Andrew Duker, and Erin Furr Stimming
Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea
Objective
To evaluate the antidepressant efficacy for depression in Huntington’s disease (HD).
Background
Depression is highly prevalent in HD. Despite frequent clinical use of antidepressants, evidence from trials remains limited and fragmented. A consolidated analysis of available trials data is needed to guide treatment decisions.
Design/Methods
PubMed was searched for trials evaluating antidepressant drugs in HD. The primary endpoint was depression (HAM‑D). Secondary endpoints included anxiety (SAS), motor function (UHDRS‑TMS), cognition (MMSE, NPI), functional capacity (UHDRS‑TFC), executive function (Trails‑B), and adverse events. Mean differences (MDs) were synthesized using inverse‑variance models, and SMD with REML.
Results
A total of 4 trials studying fluoxetine, venlafaxine, citalopram, and bupropion were found. For bupropion, only data about side effects were available. Antidepressants significantly improved depression versus control (MD −4.52, 95% CI −8.85 to −0.20; I² = 86%) [Figure 1]. Subgroup effects varied by medication (fluoxetine MD −2.87; venlafaxine MD −9.08; citalopram MD −1.90). Anxiety improved modestly (SMD −0.62, 95% CI −1.17 to −0.08) [Figure 2]. No significant effects were observed for functional (MD –0.27, 95% CI –1.37 to 0.82) [Figure 3], executive (SMD -0.12, 95% CI –1.11 to 0.88), motor (SMD –0.37, 95% CI –0.91 to 0.17), or cognitive (SMD –0.21, 95% CI –0.75 to 0.32) outcomes. Adverse event rates were similar between antidepressant and placebo groups (RR 1.86, 95% CI 0.73–4.75). Agitation (RR 0.71, 95% CI 0.17–3.01), hypomania (RR 0.95, 95% CI 0.25–3.65), fatigue (RR 0.31, 95% CI 0.01–6.85), and weight loss (RR 2.77, 95% CI 0.12–61.65) occurred at comparable frequencies.
Conclusions
Evidence indicates antidepressants yield a modest yet significant reduction in depressive symptoms in HD, though effects differ by drug class. Benefits seem confined to mood outcomes, with no consistent improvement in motor, cognitive, or functional measures. Larger, adequately powered trials are needed to guide optimal treatment strategies.
Citation
Patino J, Rissardo JP, Caprara AL, McGarry A, Walker I, Rocha N, Duker A, Furr Stimming E. Antidepressants in Huntington’s Disease: A Meta Analysis of Mood and Motor Outcomes with Placebo-controlled Trials. Mov Disord 2026;41(Suppl_1):S433-S434.
Figure 1. Forest plot of pooled MD of depressive outcomes.
Figure 2. Forest plot of pooled MD of anxiety outcomes.
Figure 3. Forest plot of pooled MD of functional capacity outcomes.