QT Interval, Antipsychotics and Correlates Among Patients with Schizophrenia: Cross-Sectional Data from the Multicentric Real-World FACE-SZ.
Drug Saf. 2025-03-15; :
DOI: 10.1007/s40264-025-01526-9
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Gerentes M(1)(2), Lajnef M(1)(2), Szöke A(1)(2), Aouizerate B(1)(3)(4), Berna
F(1)(5), Cléry M(1)(2), Chéreau I(1)(6), Coulon N(1)(7), Clauss-Kobayashi
J(1)(5), Fakra E(1)(8), Dorey JM(1)(9)(10), Dubertret C(1)(11)(12)(13), Fond
G(1)(14), Godin O(1)(2), Goze T(1)(15), Lançon C(1)(14), Leboyer M(1)(2),
Leignier S(1)(7), Llorca PM(1)(6), Mallet J(1)(11)(12)(13)(16), Misdrahi
D(1)(3)(4), Oriol N(1)(8), Rey R(1)(9)(10), Roux P(1)(17), Schorr B(15), Urbach
M(1)(17), Véry E(1)(18); FACE-SZ (FondaMental Academic Centers of
Expertise-Schizophrenia) Group; Schürhoff F(1)(2), Pignon B(19)(20)(21).
Collaborators: Andre M, Andrieu-Haller C, Aouizerate B, Berna F, Blanc O,
Capdevielle D, Cléry M, Chereau-Boudet I, Clauss-Kobayashi J, Coulon N, Dassing
R, Dorey JM, Dubertret C, Esselin A, Fond G, Gabayet F, Jarroir M, Lacelle D,
Leboyer M, Leignier S, Llorca PM, Mallet J, Metairie E, Michel T, Misdrahi D,
Passerieux C, Pignon B, Peri P, Portalier C, Rey R, Roman C, Schorr B, Schürhoff
F, Szöke A, Tessier A, Urbach M, Zinetti-Bertschy A.
Author information:
(1)FondaMental Foundation, 94010, Créteil, France.
(2)Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires « H. Mondor »,
DMU IMPACT, INSERM, IMRB, Translational Neuropsychiatry, Créteil, France.
(3)General and University Psychiatry Department, Charles Perrens Hospital,
33076, Bordeaux, France.
(4)Univ. Bordeaux, CNRS, INCIA, UMR 5287, 33000, Bordeaux, France.
(5)Department of Psychiatry, University Hospitals of Strasbourg, University of
Strasbourg, Inserm U1114, Strasbourg, France.
(6)CHU Clermont-Ferrand, Service of Psychiatry B, University of Clermont
Auvergne, Clermont-Ferrand, France.
(7)Grenoble Alpes University, Inserm U1216, CHU Grenoble Alpes, Grenoble
Institute of Neurosciences, Grenoble, France.
(8)Department of Psychiatry, University Hospital of Saint-Etienne,
Saint-Etienne, France.
(9)Le Vinatier Hospital, Schizophrenia Expert Centre, 69500, Bron, France.
(10)INSERM, U1028, CNRS, UMR5292, University Lyon 1, Lyon Neuroscience Research
Center, PSYR2 Team, 69000, Lyon, France.
(11)AP-HP, Department of Psychiatry, Louis Mourier Hospital, Colombes, France.
(12)Inserm UMR1266, Institute of Psychiatry and Neuroscience of Paris,
University Paris Descartes, Paris, France.
(13)Université Paris Diderot, Sorbonne Paris Cité, Faculté de médecine, Paris,
France.
(14)APHM, Service de psychiatrie universitaire, Aix-Marseille université,
Marseille, France.
(15)Department of Psychiatry, Psychotherapies, Art-therapy, Toulouse University
HospitalEquipe de Recherche sur les Rationalités Philosophiques et les
Savoirs-EA3051, Université de Toulouse-Jean Jaurès, Toulouse, France.
(16)Department of Psychiatry, Centre Hospitalier Universitaire d’Orléans, EPSM
du Loiret, University of Orléans, Centre Hospitalier Universitaire d’Orléans,
Orléans, France.
(17)Versailles Hospital, Department of Adult Psychiatry and Addictology, Centre
Hospitalier de Versailles, Service universitaire de psychiatrie d’adultes et
d’addictologie, Le Chesnay, Université Paris-Saclay, Université de Versailles
Saint-Quentin-En-Yvelines, DisAP-DevPsy-CESP, INSERM UMR1018, Villejuif, France.
(18)Department of Psychiatry, Psychotherapies, Art-therapy, Toulouse University
Hospital, ToNIC, Toulouse Neuroimaging Center, INSERM UMR 1214, Toulouse,
France.
(19)FondaMental Foundation, 94010, Créteil, France. .
(20)Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires « H. Mondor »,
DMU IMPACT, INSERM, IMRB, Translational Neuropsychiatry, Créteil, France.
.
(21)Hôpital Albert Chenevier, Groupe hospitalier Henri-Mondor, CHU de Créteil,
Assistance Publique-Hôpitaux de Paris (AP-HP), 40 rue de Mesly, 94000, Créteil,
France. .
BACKGROUND: The life expectancy of patients with schizophrenia is reduced,
partly due to cardiovascular diseases. Antipsychotics are associated with QT
interval prolongation, which is a risk factor for arrhythmia and cardiac arrest.
The differences between antipsychotic with regard to QT interval prolongation
are not well understood.
OBJECTIVE: The aim was to compare the QT values associated with different
antipsychotics within a real-world population of subjects with clinically stable
forms of schizophrenia.
METHODS: The FACE-SZ cohort comprises subjects with psychotic disorders,
referred to schizophrenia expert cents. QT interval was measured, as well as all
treatments (psychotropic and others). The following maintenance treatment for
schizophrenia was analysed cross-sectionally: aripiprazole, clozapine,
haloperidol, amisulpride, olanzapine, quetiapine, risperidone. Age, sex, smoking
status, body mass index, blood potassium levels, and the co-prescription of
another QT-prolonging treatment were used as adjustment factors in multivariable
linear regression analyses.
RESULTS: Among 792 patients, the mean corrected QT (QTc) interval in the sample
of patients under monotherapy was 407 ms. The mean age was 31.7 years, and the
majority were male (73.3 %). In comparison to the rest of the sample, clozapine
was associated with a longer QTc interval (β = 0.012, 95% CI [0.006-0.018]),
while aripiprazole was significantly associated with a shorter QTc interval (β =
– 0.010, 95% CI [- 0.016 to – 0.005]). Other antipsychotics were not associated
with significant variations of the QTc.
CONCLUSIONS: The prescription of antipsychotics should always be accompanied by
close monitoring of the QTc interval to prevent the risk of severe cardiac
arrhythmia, particularly concerning clozapine.
© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland
AG.
DOI: 10.1007/s40264-025-01526-9
PMID: 40088341
Conflict of interest statement: Declarations. Funding: This work was supported
by the “Investissements d’Avenir” programmes managed by the ANR under references
ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01. The funding source had no further
involvement in study design; the collection, analysis and interpretation of
data; the writing of the report or in the decision to submit the article for
publication. Conflicts of interest: The Authors have declared that there are no
conflicts of interest in relation to the subject of this study. Availability of
data and materials: Data are not available. Code availability: The code is not
available. Author contributions: MG, MoLa, FS and BP devised the study design.
Data collection was conducted by the FACE-SZ collaborators. MG and MoLa
conducted data analysis, had full access to all of the data in the study and
take responsibility for the integrity of the data and the accuracy of the data
analysis. MG and BP wrote the first draft of the manuscript. MG, AS, BA, FB, MC,
IS, NC, JCK, EF, JMD, CD, GF, OG, TG, CL, MaLe, SL, PML, JM, DM, NO, RR, PR, BS,
MU, EV, FS and BP participated in interpreting the results, manuscript editing
and figure revision. All authors approved the final version of the manuscript.
Ethics approval: The assessment protocol was approved by the ethics review board
(CPP-Ile de France IX, January 18, 2010), which required providing all patients
with an informational letter but waived the requirement for written informed
consent. Consent to participate: This study was conducted using data collected
from Expert Centres as part of regular care evaluations. The research is
classified as observational and non-interventional. It received a favourable
opinion from the French Advisory Committee on Information Processing for Health
Research (CCTIRS) and authorization from the French National Commission on
Informatics and Liberty (CNIL). Patients were informed through an information
letter, and a non-opposition form was provided to them for the collection and
use of their data for research purposes. Consent for publication: Patients were
informed through an information letter, and a non-opposition form was provided
for the collection and use of their data for research purposes.