Short‐ and long‐duration responses to levodopa during the first year of levodopa therapy

We examined the response to 2–hour levodopa infusions in 18 Parkinson's disease subjects before starting long‐term levodopa treatment and after 6 and 12 months of treatment using tapping speed as an index of bradykinesia. The long‐duration response (LDR), measured as the increase in baseline (overnight without levodopa) tapping speed, increased by 29 ± 18 at 6 months and by 35 ± 24 at 12 months. The magnitude of the short‐duration response (SDR) to a 2‐hour levodopa infusion after an overnight levodopa withdrawal did not differ at 6 and 12 months (16 ± 18 and 20±13 taps/min) from that before long‐term levodopa (21±taps/min). However, when levodopa was withheld for 3 days, it was evident that the SDR magnitude was increasing in magnitude (19, 23, and 31 taps/min at 0, 6, and 12 months). Duration of SDR did not change. A diurnal motor pattern with faster tapping speeds in the morning and slower in the evening was apparent on the days no levodopa was administered. These observations indicate (1) the LDR is responsible for much of the sustained response to levodopa during the first year of treatment, (2) the SDR magnitude increases but is obscured by the LDR, and (3) a diurnal pattern of motor function is present that may be partially responsible for the poorer motor function in the afternoons and evenings.