Orally disintegrating selegiline in Parkinson patients with dopamine agonist-related adverse effects.
OBJECTIVE
To determine whether adding orally disintegrating selegiline (ODS) while decreasing dopamine agonist (DA) dosages would reduce DA-related adverse effects (AEs) of excessive daytime sleepiness (EDS), pedal edema, hallucinations, and impulse control disorders (ICDs) without compromising efficacy in Parkinson disease (PD) patients.


METHODS
This was a 12-week open-label study of 60 PD patients with motor fluctuations and DA-related AEs of EDS, pedal edema, hallucinations, and ICDs. Orally disintegrating selegiline was initiated at 1.25 mg once daily, and down titration of the DA was started with a goal of a 50% reduction by 1 week. At week 6, ODS was increased to 2.5 mg, and further reductions of the DA were allowed if the AEs were not resolved.


RESULTS
The addition of ODS allowed a reduction in the mean daily dose of pramipexole from 2.3 to 0.5 mg and immediate-release ropinirole from 11.2 to 2.9 mg. Most subjects reported a reduction or resolution of DA-related AEs; 94% with EDS (n = 50), 73% with pedal edema (n = 26), 86% with hallucinations (n = 15), and 84% with ICDs (n = 25). Mean activities of daily living and motor scores from the Unified Parkinson's Disease Rating Scale as well as quality-of-life scores were significantly improved without an increase in daily "off" time. The most common AEs, most of which resolved after titration, were worsening of PD, nausea/vomiting, dyskinesia, increased off time, body aches, insomnia, orthostatic hypotension, and increased anxiety and depression.


CONCLUSIONS
In most subjects, the addition of ODS with decreasing dosages of DAs substantially reduced EDS, pedal edema, hallucinations, and ICDs without compromising efficacy.
Lyons
Kelly E
KE
University of Kansas Medical Center, Kansas City, KS 66160, USA. lyons.kelly@att.net
Friedman
Joseph H
JH
Hermanowicz
Neal
N
Isaacson
Stuart H
SH
Hauser
Robert A
RA
Hersh
Bonnie P
BP
Silver
Dee E
DE
Tetrud
James W
JW
Elmer
Lawrence W
LW
Parashos
Sotirios A
SA
Struck
Lynn K
LK
Lew
Mark F
MF
Pahwa
Rajesh
R
D000284:Administration, Oral; D000368:Aged; D052160:Benzothiazoles / Q000009:adverse effects / Q000627:therapeutic use; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000139:chemically induced / Q000517:prevention & control; D018491:Dopamine Agonists / Q000009:adverse effects* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D005534:Foot Diseases / Q000139:chemically induced / Q000517:prevention & control; D006212:Hallucinations / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D000077487:Pramipexole; D011788:Quality of Life; D012642:Selegiline / Q000008:administration & dosage*; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000139:chemically induced / Q000517:prevention & control; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D052160:Benzothiazoles; D018491:Dopamine Agonists; D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; C046649:ropinirole; D012642:Selegiline; D000077487:Pramipexole