Sex Differences in Levodopa‐Sparing Effect of Safinamide: Post‐hoc Findings from a Multicenter, Longitudinal, Case‐Control Study
BACKGROUND: Female sex increases the risk of levodopa-induced dyskinesias in Parkinson's disease (PD). While levodopa-sparing effects of monoamine oxidase-B inhibitors (iMAO-B) are established, sex differences in response to safinamide remain unexplored. OBJECTIVES: To evaluate sex differences in longitudinal (9 ± 3 months) changes in levodopa dose and total levodopa-equivalent daily dose (LEDD) with safinamide 100 mg. METHODS: We included 259 PD patients treated with safinamide 100 mg (cases, n = 130) or never exposed to iMAO-B (controls, n = 129). The primary outcome was the sex × treatment interaction on the change in levodopa daily dose adjusted for body weight. RESULTS: Safinamide 100 mg improved UPDRS-III scores and reduced OFF-time independently of sex. A significant sex × treatment interaction emerged for change in weight-adjusted levodopa dose and total LEDD, with greater reduction in women (p = 0.025 and 0.045, respectively). CONCLUSIONS: Safinamide 100 mg provides a larger levodopa-sparing effect in women, supporting sex-specific optimization of dopaminergic therapy in PD management.
Authors
- Margherita Canesi (ORCID: https://orcid.org/0000-0002-2642-6195)
- Emanuele Cereda (ORCID: https://orcid.org/0000-0002-0747-1951)
- Maurizio Zibetti (ORCID: https://orcid.org/0000-0002-2939-343X)
- Francesca Pistoia (ORCID: https://orcid.org/0000-0003-0790-4240)
- Andrea Pilotto (ORCID: https://orcid.org/0000-0003-2029-6606)
- Francesca Mancini (ORCID: https://orcid.org/0000-0003-4246-173X)
- Roberta Zangaglia (ORCID: https://orcid.org/0000-0002-0962-1845)
- Maria Teresa Pellecchia (ORCID: https://orcid.org/0000-0002-6217-313X)
- Nicola Modugno (ORCID: https://orcid.org/0000-0001-5243-1775)
- Salvatore Bonvegna (ORCID: https://orcid.org/0000-0003-1772-5801)
- Cristoforo Comi (ORCID: https://orcid.org/0000-0002-6862-9468)
- Chiara Sorbera (ORCID: https://orcid.org/0000-0002-5872-3119)
- Maria Chiara Sensi
- Marco Piatti
- Roberto Ceravolo
- Rosa De Micco
- Roberto Cilia
- Roberto Eleopra
- Alessio Di Fonzo (ORCID: https://orcid.org/0000-0001-6478-026X)
- Fabiana Colucci
Institutions
- University of Pisa (IT)
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- University of Salerno (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- University of Ferrara (IT)
- University of L'Aquila (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Karolinska Institutet (SE)
- Istituto Neurologico Mediterraneo (IT)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- San Salvatore Hospital (IT)
- Moriggia Pelascini Hospital (IT)
- Azienda Ospedaliera San Gerardo (IT)
- Istituto Ortopedico Gaetano Pini (IT)
- Arcispedale Sant'Anna (IT)
- IRCCS Istituto Auxologico Italiano (IT)
- Policlinico San Matteo Fondazione (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Centro Neurolesi Bonino Pulejo (IT)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- University of Turin (IT)
- University of Brescia (IT)
Publication Details
- Journal
- Movement Disorders Clinical Practice
- Published
- 2026-04-21
- DOI
- https://doi.org/10.1002/mdc3.70642
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00