Objective:To report five-year outcomes from the subthalmic nucleus (STN) deep brain stimulation (DBS) in early-stage Parkinson’s disease (PD) pilot clinical trial.Methods:The pilot was a prospective, single-blind clinical trial that randomized early-stage PD subjects (Hoehn & Yahr II off medications) to receive bilateral STN DBS plus optimal drug therapy (ODT) versus ODT alone (IDEG050016, NCT0282152, IRB040797). Subjects who completed the two-year trial participated in this observational follow-up study which included annual outpatient visits through five years. This analysis includes 28 subjects who were taking PD medications six months–four years at enrollment. Outcomes were analyzed using both proportional odds logistic regression and linear mixed effects models.Results:Early STN DBS+ODT subjects required lower levodopa equivalent daily doses (P=0.04, β = -240mg, 95%CI: -471 to -8) and had 0.06 times the odds of requiring polypharmacy at five years compared to early ODT subjects (P=0.01, OR=0.06, 95%CI: 0.00 to 0.65). The odds of having worse rest tremor for early STN DBS+ODT subjects were 0.21 times those of early ODT subjects (P<0.001, OR=0.21, 95%CI: 0.09 to 0.45). The safety profile was similar between groups.Conclusions:These results suggest that early DBS reduces the need for and complexity of PD medications while providing long-term motor benefit over standard medical therapy. Further investigation is warranted, and the FDA has approved the conduct of a prospective, multicenter, pivotal clinical trial of DBS in early-stage PD (IDEG050016).Classification of Evidence:This study provides Class II evidence that DBS implanted in early-stage Parkinson disease decreases the risk of disease progression and polypharmacy compared to optimal medical therapy alone.

This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor.