Fluoxetine for the Symptomatic Treatment of Multiple System Atrophy: The MSA-FLUO Trial
Mov Disord. 2021-04-01; 36(7): 1704-1711
DOI: 10.1002/mds.28569
Read on PubMed
Rascol O(1), Cochen de Cock V(2)(3), Pavy-Le Traon A(4), Foubert-Samier A(5), Thalamas C(6), Sommet A(6), Rousseau V(6), Perez-Lloret S(7)(8), Fabbri M(9), Azulay JP(10), Corvol JC(11), Couratier P(12), Damier P(13), Defebvre L(14), Durif F(15), Geny C(16), Houeto JL(17), Remy P(18), Tranchant C(19), Verin M(20), Tison F(21)(22), Meissner WG(21)(22)(23); MSA-FLUO Study Group.
Author information:
(1)French Reference Center for MSA, Centre d’Investigation Clinique de Toulouse
CIC1436, Departments of Neurosciences and Clinical Pharmacology, NS-Park/FCRIN
Network, NeuroToul COEN Center, University Hospital of Toulouse, INSERM,
University of Toulouse 3, Toulouse, France.
(2)Department of Neurology, Beau Soleil Clinic, Montpellier, France.
(3)EuroMov Digital Health in Motion, University of Montpellier IMT Mines Ales,
Montpellier, France.
(4)French Reference Center for MSA, Department of Neurosciences, Centre
d’Investigation Clinique de Toulouse CIC1436, UMR 1048, Institute of
Cardiovascular and Metabolic Diseases (I2MC), University Hospital of Toulouse,
INSERM, University of Toulouse 3, Toulouse, France.
(5)French Reference Centre for MSA, NS-Park/FCRIN Network, University Hospital
Bordeaux, Bordeaux, France.
(6)Centre d’Investigation Clinique de Toulouse CIC 1436, Department of Clinical
Pharmacology, University Hospital of Toulouse, INSERM, University of Toulouse 3,
Toulouse, France.
(7)Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS),
Universidad Abierta Interamericana (UAI)-Consejo Nacional de Investigaciones
Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
(8)Faculty of Medicine, Pontifical Catholic University of Argentina, Buenos
Aires, Argentina.
(9)Department of Neurosciences, Toulouse Parkinson Expert Center, Centre
d’Investigation Clinique de Toulouse CIC1436, NS-Park/FCRIN Network, University
Hospital of Toulouse, INSERM, University of Toulouse 3, Toulouse, France.
(10)Aix-Marseille Université et Assistance Publique-Hôpitaux de Marseille;
Movement Disorders Unit, NS-Park/FCRIN Network, La Timone Hospital, Marseille,
France.
(11)Sorbonne Université, Assistance Publique Hôpitaux de Paris, Inserm, CNRS,
Paris Brain Institute-ICM, Department of Neurology, Centre d’Investigation
Clinique Neurosciences, NS-Park/FCRIN Network, Pitié-Salpêtrière Hospital, Paris,
France.
(12)Centre de compétence AMS, NS-Park/FCRIN Network, CHU Limoges, Limoges,
France.
(13)CHU Nantes, Inserm, Centre d’investigation clinique 0004, Hôpital Laennec,
Nantes, France.
(14)Service de Neurologie et Pathologie du Mouvement, NS-Park/FCRIN Network, CHU
Lille, INSERM 1172, University of Lille, Lille, France.
(15)Neurology Department, University Hospital Center, Clermont-Ferrand, France;
NS-Park/FCRIN Network, Equipe d’Accueil 7280 Clermont Auvergne University,
Clermont-Ferrand, France.
(16)Department of Neurology, EuroMov, University of Montpellier, CHRU
Montpellier, Montpellier, France.
(17)Service de Neurologie, Centre Expert Parkinson, centre de compétence AMS,
NS-Park/FCRIN Network, CHU de Limoges, Limoges cedex, France.
(18)Centre Expert Parkinson, NS-Park/FCRIN Network, CHU Henri Mondor, AP-HP,
Equipe NPI, IMRB, INSERM et Faculté de Santé UPE-C, Créteil, France.
(19)Service de Neurologie, NS-Park/FCRIN Network, Hôpitaux Universitaires de
Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire,
INSERM-U964/CNRS-UMR7104; Fédération de Médecine Translationnelle de Strasbourg,
Université de Strasbourg, Strasbourg, France.
(20)Centre Expert Parkinson-Bretagne, NS-Park/FCRIN Network, University Hospital
of Rennes, EA 4712 “Behavior and Basal Ganglia”, University of Rennes 1, Institut
des Neurosciences Cliniques de Rennes, Rennes, France.
(21)Service de Neurologie des Maladies Neurodégénératives, French Reference
Center for MSA, NS-Park/FCRIN Network, CHU Bordeaux, Bordeaux, France.
(22)University of Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, France.
(23)Department of Medicine, University of Otago, Christchurch, and New Zealand
Brain Research Institute, Christchurch, New Zealand.
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.
© 2021 International Parkinson and Movement Disorder Society.