Long Duration Response in Parkinson's Disease: Levodopa Revisited

Werner Poewe; Alberto J. Espay


Brain. 2020;143(8):2332-2335. 

In This Article

There is no Decline in the Response to Levodopa Over Time

Many patients and even some neurologists may still have reservations about initiating levodopa early in the disease because of the concern that the benefit may be limited and therefore best saved for later stages. That this is clearly not the case is again illustrated in this study from Africa: the first ever dose of levodopa produced an improvement of 40% in the motor UPDRS score and this response progressively increased over the 2 years of follow-up. The design of this study provides further impressive evidence for the persistence of the levodopa effect: the authors found no difference between the mean UPDRS motor scores in the ON condition after the first ever dose of levodopa and the corresponding practically defined OFF scores after 12 h of levodopa withdrawal at the 1-year follow-up—i.e. a strong 'long-duration' component of the levodopa response (Figure 1).

Figure 1.

'Natural' versus overnight OFF. The long-duration response (LDR) effect contributes to a lower baseline motor severity after an overnight (~12 h) levodopa withdrawal than the baseline motor severity prior to levodopa initiation ('natural OFF'). (A) The cohort studied by Cilia etal. received no treatment until ~7 years had elapsed, with levodopa treatment there was marked decrease in the motor severity, almost immediately generating a robust LDR. (B) Schematic depiction of two single-dose levodopa challenges after initiation and after ~4 years of levodopa showing the relative changes in SDR and LDR components as well as the early and persistent dyskinesia burden.