Timely levodopa (LD) administration prolongs survival in Parkinson's disease

Levodopa (LD) is the most effective drug for symptomatic control of Parkinsonism (PS). As prolonged LD therapy leads to response failure; is associated with adverse effects; may accelerate disease process, and its impact on life expectancy is controversial, delaying LD use has been recommended. We studied 934 PS cases including 859 Parkinson's disease (PD) patients over twenty-two years (1968-1990) to identify: (i) survival change coincident with widespread LD use and (ii) the critical level of disease severity when LD influences survival. Survival was measured from the date of first assessment until the last evaluation for a cumulative 3563 person- years of follow-up and compared with that expected in the general population of the same age, sex and year of birth. A Cox regression model was used to identify independent clinical predictors of survival. The observed to expected survival was reduced significantly in PS. Dementia and advanced disability at initial assessment and the final non-PD diagnosis, each was independently associated with poor survival. Survival improved significantly coincident with the widespread unrestricted access to LD (p = 0.024 -< 0.001) compared to pre-levodopa era cases. Life expectancy was longest in the more recent non-demented PD cases. When the major disease and treatment related factors were considered the timely use of levodopa in the recent cases resulted in improved survival compared to the earlier cases who received LD later in the course of illness. When LD naive cases were considered, survival was significantly reduced if the drug was delayed until Stage 3 Hoehn and Yahr, but not so if the patients remained untreated during Stages 1 and 2 Hoehn and Yahr [1]. Life expectancy in PD has increased significantly since the widespread use of LD. This benefit is evident only if LD therapy is initiated before the patient reaches Stage 2.5 disability [2].