Fluoxetine for the Symptomatic Treatment of Multiple System Atrophy: The MSA-FLUO Trial

Olivier J. Rascol (1, 2, 3) , Valérie Cochen de Cock (4, 5) , Anne Pavy-Le Traon (6, 1, 2) , Alexandra Foubert-Samier (7, 1) , Claire Thalamas (1, 8) , Agnes Sommet (1, 8) , Vanessa Rousseau (1, 8) , Santiago Perez-Lloret (9, 10) , Margherita Fabbri (1, 2, 8) , Jean Philippe Azulay (11, 2) , Jean-Christophe Corvol (12, 13, 2) , Philippe Couratier (14, 2) , Philippe Damier (15, 16) , Luc Defebvre (17, 18, 2) , Franck Durif (19, 20, 2) , Christian Geny (4, 21) , Jean-Luc Houeto (14, 2) , Philippe Remy (22, 23, 2) , Christine Tranchant (24, 2, 25, 26) , Marc Verin (27, 28, 2) , François Tison (29, 7, 2) , Wassilios G Meissner (29, 7, 2, 30)

1 CIC 1436 - Centre d'investigation clinique de Toulouse
2 NS-Park/FCRIN Network
3 NeuroToul - Centre d’Excellence en Maladies Neurodégénératives
4 Euromov DHM - EuroMov - Digital Health in Motion
5 Clinique Beau Soleil [Montpellier]
6 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
7 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
8 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
9 CONICET - Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires]
10 UCA - Pontifical Catholic University of Argentina
11 TIMONE - Hôpital de la Timone [CHU - APHM]
12 ICM - Institut du Cerveau = Paris Brain Institute
13 CHU Pitié-Salpêtrière [AP-HP]
14 CHU Limoges
15 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
16 Hôpital Nord Laennec [CHU Nantes]
17 LilNCog - Lille Neurosciences & Cognition - U 1172
18 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
19 CHU Clermont-Ferrand
20 NPsy-Sydo - Neuro-Psycho Pharmacologie des Systèmes Dopaminergiques sous-corticaux
21 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
22 IMRB - Institut Mondor de Recherche Biomédicale
23 CHU Henri Mondor [Créteil]
24 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
25 FMTS - Fédération de Médecine Translationnelle de Strasbourg
26 HUS - Les Hôpitaux Universitaires de Strasbourg
27 Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes]
28 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
29 IMN - Institut des Maladies Neurodégénératives [Bordeaux]
30 University of Otago [Dunedin, Nouvelle-Zélande]

BACKGROUND: There are no effective treatments for multiple system atrophy (MSA). OBJECTIVE: The objective of this study was to assess the efficacy and safety of the serotonin reuptake inhibitor fluoxetine (40 mg/d) for the symptomatic treatment of MSA. METHODS: This was a double-blind, parallel-group, placebo-controlled, randomized trial in patients with "probable" MSA. The primary outcome was the change from baseline to week 12 in the mean total score of the Unified MSA Rating Scale (UMSARS Parts I + II). Secondary outcomes included change from baseline to week 6 in total UMSARS, and change from baseline to week 12 in the Scales for Outcomes in Parkinson Disease-Autonomic Dysfunction, Beck Depression Inventory, and different domains of the MSA-Quality of Life Questionnaire. Exploratory outcomes included change from baseline to week 12 in the UMSARS Parts I and II separately and change from baseline to week 24 in the total UMSARS score. RESULTS: A total of 81 patients were randomly assigned, with no significant difference in the primary outcome (-2.13 units [95% confidence interval, CI, -4.55 to 0.29]; P = 0.08). There was a greater reduction on fluoxetine in the change from baseline to 12-week in UMSARS Part II (exploratory outcome: -1.41 units [95% CI, -2.84; 0.03]; p = 0.05) and in MSA-QoL emotional/social dimension (secondary outcome: -6.99 units [95% CI, -13.40; -0.56]; p < 0.03). A total of 5 deaths occurred (3 on fluoxetine and 2 on placebo). CONCLUSION: The MSA-FLUO failed to demonstrate fluoxetine superiority over placebo on the total UMSARS score, whereas trends in motor and emotional secondary/exploratory outcomes deserve further investigation. © 2021 International Parkinson and Movement Disorder Society.

Mots clés: fluoxetine; multiple system atrophy; clinical trial; placebo; symptomatic treatment

Domaines: Sciences du Vivant [q-bio]

Olivier J. Rascol, Valérie Cochen de Cock, Anne Pavy-Le Traon, Alexandra Foubert-Samier, Claire Thalamas, et al.. Fluoxetine for the Symptomatic Treatment of Multiple System Atrophy: The MSA-FLUO Trial. Movement Disorders, 2021, 36 (7), pp.1704-1711. ⟨10.1002/mds.28569⟩. ⟨hal-03190779⟩