Multicenter retrospective study on perceived effectiveness, reported side effects, and cognitive outcomes of SSRIs in 22q11.2 deletion syndrome
Abstract
22q11.2 deletion syndrome (22q11DS) markedly increases risk of psychiatric disorders, including anxiety and mood disorders, and is associated with a spectrum of cognitive impairment, from borderline functioning to intellectual disability, with cognitive decline frequently reported. Despite widespread use of selective serotonin reuptake inhibitors (SSRIs) in 22q11DS, evidence regarding their safety, effectiveness, and potential effects on cognitive trajectories remains limited. We conducted a retrospective, observational multicenter study across nine international centers, including cross-sectional and longitudinal analyses. In the cross-sectional sample of 190 SSRI-treated individuals with 22q11DS (6-56 years), retrospective data on SSRI type, indication, perceived effectiveness, and side effects were analyzed descriptively (40-190 cases across variables). In the longitudinal analyses, intellectual quotient (IQ) trajectories were compared between 101 SSRI-treated and 213 SSRI-untreated participants (4-34 years) using mixed-model regression analyses. SSRIs were mainly prescribed for mood and/or anxiety disorders (94%) and were rated as overall effective in 71% of cases with available data, with side effects reported in 25%. SSRI-treated participants exhibited stable or modestly increasing IQ trajectories, whereas SSRI-untreated participants showed decreasing trajectories over time. In exploratory analyses, concomitant psychostimulant treatment was associated with the most favorable IQ trajectories. Treatment duration, but not dosage, was positively associated with IQ change. These findings suggest that the effects of SSRI treatment in individuals with 22q11DS may extend beyond symptom management. Controlled prospective studies are needed to confirm these findings and determine underlying mechanisms.
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Authors: Caren Latrèche, Valentina Mancini, Marija Dvojakovska, Leila Kushan, Fatouma Mchangama, Feryal Tairi, Tal Cohen, J. Spapens, Lieke Reijn, Covadonga M. Díaz‐Caneja, Hayford Acheampong, Lotte Troch, Elfi Vergaelen, Annick Vogels, Ann Swillen, Claudia Vingerhoets, Erik Boot, Celso Arango, Fleur Velders, Ania Fiksinski, Thérèse van Amelsvoort, Doron Gothelf, Carrie E. Bearden, Boris Chaumette, Maude Schneider, Stéphan Eliez
Institutions: University of California, Los Angeles, KU Leuven, University of Oxford, University Health Network, Inserm, Instituto de Salud Carlos III, Maastricht University, Université Paris Cité, Sorbonne Paris Cité, University of Geneva, Délégation Paris 5, Centre National de la Recherche Scientifique, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Salud Mental, Hospital Universitario La Paz, Tel Aviv University, McGill University, Toronto General Hospital, Sheba Medical Center, Foundation for laboratory medicine, 's Heeren Loo, NeuroDiderot, University Medical Center Utrecht, MRC Brain Network Dynamics Unit, Centre Hospitalier Sainte-Anne, Wilhelmina Children's Hospital, Hospital General Universitario Gregorio Marañón, Institut de Psychiatrie et Neurosciences de Paris