While levodopa is the most effective symptomatic treatment for Parkinson’s disease (PD), it is associated with an increased MC risk in the first five years of treatment compared to DA first therapy which is less effective/has side effects. 

We performed a large retrospective cohort study of 1627 PD patients attending DBS clinic at Toronto Western Hospital, Canada (03/2004-02/2022). PD patients who underwent globus pallidus interna (GPi)/subthalamic nucleus (STN) DBS in  ≥2005 to address disabling MC were included.

438 patients met the inclusion criteria (352 STN/86 GPi DBS). The median disease duration was 9 years (2-30). 312 received levodopa first/126 a DA (no significant difference in the target selection/amantadine use). The duration from the first treatment-DBS assessment (L-dopa median 8, IQR 4; DA median 9, IQR 4, p=0.64) or DBS surgery (L-dopa median 10, IQR 5; DA median 10, IQR 5, p=075), did not differ (adjusted for age-at-diagnosis, gender, amantadine).

In two longest studies, only 1/5-1/3 of the original cohort after 14-15 years of follow-up was available for an assessment (conducted before DBS was an established MC treatment in PD). Large studies including younger patients at greater risk of MC/with intermediate disease duration, are lacking. 49% of our patients was diagnosed at age ≤ 50, had a long follow up, sufficient to allow the development of disabling MC, but without major mortality/morbidity. Our final sample size was >2x larger than three of the longest studies combined (Hely;2005/Hauser;2007/Katzenschlager;2008)

This is the only study to date to evaluate the duration between L-dopa/DA first treatment and the MC development of sufficient severity to warrant DBS consideration. The results suggests these are independent of the first treatment type.