Abstract | IMPORTANCE: OBJECTIVE: DESIGN, SETTING, AND PARTICIPANTS: The ADAGIO study was a double-blind, placebo-controlled, delayed-start trial of rasagiline in de novo PD. In this exploratory post hoc analysis, we analyzed patients taking an antidepressant during the 36-week phase 1 period, in which patients were randomized to rasagiline (1 or 2 mg/d) or placebo. MAIN OUTCOMES AND MEASURES: We evaluated the change in NMSs in patients taking an antidepressant and rasagiline compared with those taking placebo. The NMSs were assessed by Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Nonmotor Experiences of Daily Living, the original Unified Parkinson's Disease Rating Scale, and the Parkinson Fatigue Scale. RESULTS: A total of 191 of the 1174 patients (16.3%) were treated with antidepressants during phase 1 and provided efficacy data. Depression and cognition scores revealed significantly less worsening in the rasagiline group compared with the placebo group (differences in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale item-adjusted means [SEs], -0.19 [0.10], P = .048, and -0.20 [0.05], P < .001, respectively). Parkinson Fatigue Scale (mean [SE] difference, -0.42 [0.09], P < .001) and daytime sleepiness (mean [SE] difference, -0.24 [0.09], P = .006) scores also revealed significantly less worsening in the rasagiline group compared with placebo. There was a nonsignificant trend toward less worsening in apathy and no significant between-group differences in anxiety or sleep. The effect on depression remained significant after controlling for improvement in motor symptoms (mean [SE] difference, -0.23 [0.09], P = .009). There were no serious adverse events in the combined rasagiline- antidepressant group suggestive of serotonin syndrome. CONCLUSIONS AND RELEVANCE: The combination of rasagiline and antidepressants in patients with de novo PD is associated with reduced worsening of a range of NMSs in preliminary analyses. Adverse effects appear uncommon with this combination. These findings suggest a role for dopamine-enhancing therapies in NMSs in early PD and encourage further study and confirmation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00256204.
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Authors | Kara M Smith, Eli Eyal, Daniel Weintraub, ADAGIO Investigators |
Journal | JAMA neurology
(JAMA Neurol)
Vol. 72
Issue 1
Pg. 88-95
(Jan 2015)
ISSN: 2168-6157 [Electronic] United States |
PMID | 25420207
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antidepressive Agents
- Indans
- Neuroprotective Agents
- rasagiline
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antidepressive Agents
(therapeutic use)
- Apathy
- Depression
(drug therapy, etiology)
- Disease Progression
- Double-Blind Method
- Drug Therapy, Combination
- Fatigue
- Female
- Humans
- Indans
(therapeutic use)
- Male
- Middle Aged
- Neuroprotective Agents
(therapeutic use)
- Parkinson Disease
(complications, drug therapy)
- Psychiatric Status Rating Scales
- Severity of Illness Index
- Sleep
- Treatment Outcome
- Wakefulness
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