Objective: (i) To collect all the levodopa equivalent doses (LED) formulae and references used in clinical trials in Parkinson’s disease (PD) since the publication of Tomlinson’s LED in 2010 [1], (ii) to evaluate the frequency of utilization of Tomlinson’s LED among all the LED formulae during the last 7 years and (iii) to observe the major difference per antiparkinsonian drugs among all the formulae for which we drawn up an inventory of LEDs.

Background: LEDs provide a summary of the total daily antiparkinsonian medications with highly variable methods of calculation. In 2010, Tomlinson et al published a systematic review providing conversion formulae for the antiparkinsonian drugs, based on the mean of the previous LED proposed for each molecule. Seven years after the publication of this review, is this method consensual in clinical research ?

Methods: We conducted a search of the published articles between January 2010 and June 2017, in Pubmed electronic database. We chose three different associations of search terms: (i) “levodopa” or “L dopa” or “L-dopa” or “Ldopa” and “Parkinson” and clinical trials; (ii) “Apomorphine infusion” or “LCIG” (levodopa continuous intestinal gel) and “Parkinson”; (iii) “levodopa” and “equivalent” and “Parkinson”. We excluded non English written articles, articles in which LEDs were not used and articles using LEDs but without any available references allowing to find the conversion formula and to justify their calculation. If the formula was explained in a previous article published before 2010, the article was included.

Results: 472 articles were identified from our PubMed searches. 293 were excluded (196 did not use LEDs, 97 did not give references or calculation formulae). In the 179 remaining articles, from 2010 to 2017, Tomlinson’s LEDs became more cited (32% of analyzed articles in 2012 versus 86% in 2017). We identified 48 articles describing a calculation method either with a proper reference or without any reference to justify these formulae. Among these articles, 11 had adapted Tomlinson’s LED. Regarding the 37 other LEDs formulae, there is a variability for each LED drug compared to Tomlinson’s factors except for pramipexole, LCIG, bromocriptine and selegiline.

Conclusions: Although Tomlinson is largely cited, no consensus seems to be obtained for all the antiparkinsonian drugs. Another consensus may be needed, all the more as there are new antiparkinsonian drugs which are not referred in Tomlinson’s LEDs calculation.

References: [1] Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Movement disorders : official journal of the Movement Disorder Society 2010;25(15):2649-2653.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/7-years-later-are-the-tomlinsons-levodopa-dose-equivalencies-proposed-consensual/