Affiliations: [a] Department of Neurology, Hadassah Medical Center and the Hebrew University, Jerusalem, Israel
| [b] School of Pharmacy, Faculty of Medicine, the Hebrew University, Jerusalem, Israel
| [c] Department of Medical Neurobiology (Physiology), Institute of Medical Research – Israel-Canada, the Hebrew University - Hadassah Medical School and the Edmond and Lily Safra Center for Brain Research, the Hebrew University, Jerusalem, Israel
| [d] Jerusalem Mental Health Center, Hebrew University Medical School, Jerusalem, Israel
| [e] Department of Neurosurgery, Hadassah Medical Center and the Hebrew University, Jerusalem, Israel
Correspondence to: David Arkadir, MD, PhD, Department of Neurology, Hadassah Medical Center and the Hebrew University, Jerusalem, Israel. Tel.: +972 2 6777111; Fax: +972 2 6437782; E-mail: [email protected].
Note:  These authors contributed equally to this work.
Abstract: Background:A wide variety of conversion factors for a levodopa-equivalent-dose (LED) have been proposed for each Parkinson’s disease (PD) medication. The currently-used set of conversion factors is based on studies that relied on subjective experience or theoretical assumptions. This set was never validated in patients receiving polytherapy. Objectives:To use real-life data to identify an optimal set of conversion factors independent of prior assumptions regarding clinical efficacy of different medications. Methods:Retrospective analysis of data from 206 cognitively-preserved patients with advanced PD receiving polytherapy before deep brain stimulation (DBS) surgery. A nonlinear automated problem solver was used to find a set of conversion factors that, when applied, minimized the coefficient of variation of LEDs in a relatively homogenous cohort of patients. Results:Independent and model-free evaluation of a wide range of possible sets of conversion factors to LED suggested a set of normalized conversion factors for immediate release levodopa (1.00), controlled release levodopa (0.88), and amantadine (1.23). A minimal clinical benefit of entacapone was observed for patients with motor fluctuations. Our analysis could not detect conversion factors for dopamine agonists and MAO-B inhibitors, possibly because their clinical contribution when added to levodopa is limited. Conclusions:Independent from previous studies and prior assumptions we show that the currently-used LED conversion factors for immediate release levodopa, controlled release levodopa and amantadine are largely correct and that dopamine agonists, MAO-B inhibitors and entacapone, given in addition to levodopa, have little additional clinical value for PD patients with motor fluctuations.