Optimizing Treatment in Undertreated Late-Stage Parkinsonism: A Pragmatic Randomized Trial.

BACKGROUND Treatment of patients with late-stage parkinsonism is often sub-optimal. OBJECTIVE To test the effectiveness of recommendations by a movement disorder specialist with expertise in late-stage parkinsonism. METHODS Ninety-one patients with late-stage parkinsonism considered undertreated were included in apragmatic multi-center randomized-controlled trial with six-month follow-up. The intervention group received a letter with treatment recommendations to their primary clinician based on an extensive clinical assessment. Controls received care as usual. The primary outcome was the Unified Parkinson Disease Rating Scale (UPDRS)part-II (Activities of Daily Living).Other outcomes included quality-of-life (PDQ-8), mental health (UPDRS-I), motor function (UPDRS-III), treatment complications (UPDRS-IV), cognition (Mini-mental-state-examination), non-motor symptoms (Non-Motor-Symptoms-scale), health status (EQ-5D-5L) and levodopa-equivalent-daily-dose (LEDD). We also assessed adherence to recommendations. In addition to intention-to-treat analyses, aper-protocol analysis was conducted. RESULTS Sample size calculation required 288 patients, but only 91 patients could be included. Treating physicians followed recommendations at least partially in 37(64%) patients. The intention-to-treat analysis showed no difference in primary outcome (between-group difference = -1.2, p = 0.45), but there was greater improvement for PDQ-8 in the intervention group (between-group difference = -3.7, p = 0.02). The per-protocol analysis confirmed these findings, and showed less deterioration in UPDRS-part I, greater improvement on UPDRS-total score and greater increase in LEDD in the intervention group. CONCLUSIONS The findings suggest that therapeutic gains may be reached even in this vulnerable group of patients with late-stage parkinsonism, but also emphasize the need for better strategies to implement specialist recommendations to further improve outcomes.