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Journal of the Neurological Sciences 248 (2006) 78 – 83
www.elsevier.com/locate/jns

Rasagiline-associated motor improvement in PD occurs without worsening

of cognitive and behavioral symptoms B

*
L. Elmer , S. Schwid, S. Eberly, C. Goetz, S. Fahn, K. Kieburtz, D. Oakes, K. Blindauer,
P. Salzman, S. Oren, U.L. Prisco, M. Stern, I. Shoulson

Parkinson Study Group TEMPO and PRESTO Investigators 1
Medical College of Ohio, Department of Neurology, 3120 Glendale Ave., Toledo, OH 43614, United States
Available online 7 July 2006

Abstract
Background: Cognitive and behavioral adverse events (AEs) such as hallucinations, confusion, depression, somnolence and other sleep
disorders commonly limit effective management of motor symptoms in PD. Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a novel,
second-generation, selective, irreversible monoamine oxidase type B inhibitor, demonstrated in monotherapy and adjunctive trials to be
effective for PD with excellent tolerability.
Methods: The occurrence of cognitive and behavioral AEs and the change from baseline in the Unified Parkinson’s Disease Rating Scale
(UPDRS) part I mental subscores were reviewed in two multicenter, randomized, placebo-controlled, 26-week trials of rasagiline for early
and moderate-to-advanced patients with PD. The UPDRS is a multi-item rating scale specific to PD; part I rates the patient’s intellectual
impairment, thought disorders, depression and motivation/initiative.
Results: The TEMPO study evaluated rasagiline monotherapy in early PD patients (n =404). The PRESTO study evaluated rasagiline as
adjunctive therapy in moderate-to-advanced PD patients with motor complications who were receiving optimized levodopa/carbidopa
(n =472). In the analysis of adverse event reporting for both studies, no cognitive and behavioral AE in either the rasagiline 1 mg or placebo
groups exceeded 10% of the study population and the frequency differences between rasagiline 1 mg and placebo never exceeded 3%. There
was no adverse effect on the UPDRS mental subscore relative to placebo in either of the two studies.
Conclusion: Rasagiline 1 mg once daily improves PD symptoms and motor fluctuations in early and moderate-to-advanced PD patients
without causing significant cognitive and behavioral AE or adverse changes in mentation, behavior and mood.
D 2006 Elsevier B.V. All rights reserved.

Keywords: Parkinson’s disease; Rasagiline; Tolerability; Efficacy

1. Introduction

i
TEMPO and PRESTO studies were supported in the United States by Parkinson’s disease is a progressive, neurodegenerative
Teva Neuroscience, Inc., in partnership with Eisai, Inc., and by TEVA disorder characterized by bradykinesia, rigidity, rest tremor
Pharmaceutical Industries Ltd. and Lundbeck A/S. No additional funding and postural instability. Treatment of the underlying
was provided for the data analysis pertinent to this report.
* Corresponding author. Tel.: +1 419 383 3544; fax: +1 419 383 3093. neurochemical deficit, dopamine deficiency, is largely
E-mail address: lelmer@meduohio.edu (L. Elmer). successful for most patients due to long-standing therapies
1
The Parkinson Study Group investigators are listed in the appendix. such as levodopa and multiple new pharmacological
From Medical University of Ohio (L.E.), Toledo, OH; University of alternatives [3,4]. However, drug-induced cognitive and
Rochester (S.S., S.E., K.K., D.O., I.S.), Rochester, NY; Rush University
behavioral adverse events such as hallucinations, confusion,
Medical Center (C.G.), Chicago, IL; Columbia University (S.F.), New
depression, somnolence, and other sleep disorders com-
York, NY; Medical College of Wisconsin (K.B.), Milwaukee, WI; TEVA
monly limit effective management of motor symptoms in
Neuroscience (P.S., U.L.P.) Kansas City, MO; TEVA Pharmaceuticals
(S.O.) Netanya, Israel; University of Pennsylvania (M.S.), Philadelphia, PA. Parkinson’s disease (PD) [5–7].
0022-510X/$ - see front matter D 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jns.2006.05.014