title: Levodopa improves physical fatigue in Parkinson's disease: a double-blind, placebo-controlled, crossover study.
abstract: We quantitatively investigated the effect of carbidopa/levodopa (25/100) on physical fatigue during finger tapping and force generation in a double-blind, placebo-controlled crossover study. Parkinson's disease (PD) subjects were randomly assigned to carbidopa/levodopa or placebo for Visit 1 or 2 and participated in the following two studies: (1) Finger tapping. Twenty-five PD patients used their index fingers to strike two keys 20 cm apart on a musical instrument digital interface (MIDI) keyboard. The slopes of the regression line of dwell time and movement time were used to assess the rate of fatigue development. (2) Force generation. Twelve PD patients contracted the wrist extensors maximally to obtain a baseline maximum voluntary contraction (BMVC) force. Then they repetitively contracted the wrist extensors at 50% of the BMVC for 7 seconds and rested for 3 seconds. An interval maximum voluntary contraction (IMVC) was measured every three repetitions. Fatigue was defined as an IMVC of less than 60% of the BMVC. The slope of the regression line of IMVC was used to assess the rate of force decline. These two studies were repeated 1 hour after carbidopa/levodopa (25/100) or placebo. Subjects filled out the Multidimensional Fatigue Inventory (MFI) at the beginning of the first visit. Results showed that the slope of dwell time decreased with levodopa but not with placebo (P = 0.004). The rate of force decline also decreased with levodopa but not with placebo (P = 0.01). The subscores in the dimension of physical fatigue in the MFI did not correlate with the rate changes in dwell time or the rate changes in force decline. We concluded that (1) levodopa improves physical fatigue in finger tapping and force generation, (2) physical fatigue in Parkinson's disease is at least partially related to dopamine deficiency, and (3) the MFI measures different aspects of physical fatigue compared with those measured by finger tapping and force generation.
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, Oregon 97239, USA. louja@ohsu.edu
authors.forename: Jau-Shin
authors.initials: JS
authors.lastname: Lou
authors.forename: Greg
authors.initials: G
authors.lastname: Kearns
authors.forename: Theodore
authors.initials: T
authors.lastname: Benice
authors.forename: Barry
authors.initials: B
authors.lastname: Oken
authors.forename: Gary
authors.initials: G
authors.lastname: Sexton
authors.forename: John
authors.initials: J
authors.lastname: Nutt
mesh_terms: D000368:Aged; D018592:Cross-Over Studies; D015259:Dopamine Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005385:Fingers / Q000502:physiology; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D009068:Movement / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy; D011597:Psychomotor Performance / Q000187:drug effects; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D015259:Dopamine Agents; D004338:Drug Combinations; D007980:Levodopa