title: Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson' s disease.
abstract: Putative neuroprotective agents for Parkinson's disease can be assessed in untreated patients using progression of clinical disability as an index of disease progression. To avoid the confound associated with symptomatic therapy, progression of the underlying disease can be assessed by evaluating the progression of clinical disability from an untreated baseline to a final visit following wash-out of symptomatic medication. In this type of analysis it is critical to use a washout of sufficient duration to ensure elimination of symptomatic effects. To assess the time course of resolution of symptomatic effects, we evaluated 31 patients at days 1, 8, and 15 following discontinuation of levodopa/carbidopa and bromocriptine. Mean total Unified Parkinson's Disease Rating Scale scores (+/- standard error) increased (worsened) by 7.4+/-1.5 from day 1 to day 15 (p <0.0001), 4.5+/-1.2 from day 1 to day 8 (p = 0.0009), and 2.9+/-1.0 from day 8 to day 15 (p = 0.01). We conclude that a wash-out of at least 2 weeks is required to eliminate the symptomatic effects of levodopa/carbidopa and bromocriptine in patients with early Parkinson's disease.
authors.affiliation: Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa 33606, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Hauser
authors.forename: W C
authors.initials: WC
authors.lastname: Koller
authors.forename: J P
authors.initials: JP
authors.lastname: Hubble
authors.forename: T
authors.initials: T
authors.lastname: Malapira
authors.forename: K
authors.initials: K
authors.lastname: Busenbark
authors.forename: C W
authors.initials: CW
authors.lastname: Olanow
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001971:Bromocriptine / Q000009:adverse effects* / Q000627:therapeutic use; D002230:Carbidopa / Q000009:adverse effects* / Q000627:therapeutic use; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D012642:Selegiline / Q000009:adverse effects / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis*
chemical_list: D000978:Antiparkinson Agents; D012642:Selegiline; D001971:Bromocriptine; D007980:Levodopa; D002230:Carbidopa