- Design
- Analysis of two prospective multicentre cohorts
- Population
- 25,602 patients (NS-Park) and 1,441 (PPMI) with Parkinson disease
- Primary outcome
- Freezing-of-gait severity and incidence by levodopa exposure
- Effect
- Adjusted odds ratios 1.84 (95% CI 0.94-3.61) and 0.76 (0.38-1.51), both non-significant
Whether levodopa exposure contributes to freezing of gait in Parkinson disease has long been debated, confounded by the fact that patients on more levodopa tend to have longer, more severe disease. This analysis of two large prospective cohorts, NS-Park and PPMI, totalling over 27,000 patients, tried to separate the two.
In unadjusted analysis, levodopa looked associated with more freezing. After adjustment for disease duration, Hoehn and Yahr stage and motor score, that association disappeared: the effect of levodopa on freezing severity was non-significant in both cohorts, and there was no significant link with new-onset freezing. What remained strongly associated were disease duration and severity.
The practical reassurance is that there is no good evidence to withhold or limit levodopa out of fear of causing freezing. Freezing tracks the disease, not the drug, and under-treating motor symptoms to avoid it is not supported.
- Two prospective Parkinson cohorts, NS-Park and PPMI, over 27,000 patients combined.
- An apparent link between levodopa and freezing disappeared after adjustment.
- Adjusted odds ratios for freezing severity were non-significant in both cohorts.
- Disease duration and severity were the consistent drivers of freezing.
- Do not withhold or limit levodopa to avoid freezing of gait.
Why it matters
It removes a common reason clinicians under-dose levodopa, which risks leaving motor symptoms undertreated.
Don't overread it
These are observational cohorts; a non-significant association after adjustment is reassurance, not proof that levodopa has no effect in any patient.
The statistics, in plain English
The adjusted odds ratios (1.84 in one cohort, 0.76 in the other) point in opposite directions and both cross 1.0, so no consistent effect survived adjustment. Meanwhile disease duration carried odds ratios of 4 to 7, showing where the real signal lies.
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