Jean-Baptiste Quilichini1, Alexis Revet2, Philippe Garcia1, Régis Bouquié3, Jacques Hamard1, Antoine Yrondi4, François Montastruc5. 1. Department of Medical and Clinical Pharmacology, Centre of PharmacoVigilance and Pharmacoepidemiology, Toulouse University Hospital (CHU), Faculty of Medicine, Toulouse, France; Centre d'Investigation Clinique 1436, Team PEPSS « Pharmacologie En Population cohorteS et biobanqueS », Toulouse University Hospital, France. 2. Centre d'Investigation Clinique 1436, Team PEPSS « Pharmacologie En Population cohorteS et biobanqueS », Toulouse University Hospital, France; Department of Child and Adolescent Psychiatry, Faculty of Medicine, Toulouse University Hospital (CHU), Toulouse, France. 3. Laboratoire de Biologie Médicale, Centre Hospitalier Léon-Jean Grégory, avenue du Roussillon, 66330, Thuir, France. 4. Department of Medical Psychiatry, Toulouse University Hospital (CHU), Faculty of Medicine, Toulouse, France; Treatment Resistant Depression Expert Center, FondaMental, Toulouse, France; ToNIC Toulouse NeuroImaging Center, University Paul Sabatier Toulouse, INSERM, Toulouse, France. 5. Department of Medical and Clinical Pharmacology, Centre of PharmacoVigilance and Pharmacoepidemiology, Toulouse University Hospital (CHU), Faculty of Medicine, Toulouse, France; Centre d'Investigation Clinique 1436, Team PEPSS « Pharmacologie En Population cohorteS et biobanqueS », Toulouse University Hospital, France. Electronic address: francois.montastruc@univ-tlse3.fr.
Abstract
BACKGROUND: While case reports and clinical trials reported withdrawal syndrome after reduction and/or discontinuation of antidepressant drugs, no large study has been conducted to compare the risk between the different antidepressants. METHODS: Using data recorded from January 1st, 1988, and December 31st, 2020 in VigiBase®, the World Health Organization's Global Individual Case Safety Reports database, we performed disproportionality analysis to investigate the risk of reporting withdrawal syndrome in patients treated by short half-life antidepressants compared with patients treated by long half-life antidepressants. In addition, we aimed to better inform clinical practice by comparing 15 antidepressants for the risk of reporting withdrawal syndrome. RESULTS: Among the 338,498 reports with antidepressants of interest, we found 15,507 cases of withdrawal syndrome. Short half-lives antidepressants were associated with an increased risk of reporting a withdrawal syndrome compared to long half-life antidepressants (ROR 5.38; 95% CI 5.16-5.61). The risk was higher for 18-44 years old (ROR 6.88; 95% CI 6.17-7.62), women (ROR 1.38; 95% CI 1.33-1.43) and patients treated with Paroxetine, Desvenlafaxine, Venlafaxine and Duloxetine. LIMITATIONS: The limitations of this study stem from the case-reporting process. CONCLUSIONS: This large observational study in a real-world setting suggests that the use of short half-life antidepressants increases the risk of reporting withdrawal syndrome compared to long half-life antidepressants. Among the most common antidepressants, paroxetine and serotonin-noradrenaline reuptake inhibitors are associated with a greater risk of reporting withdrawal syndrome, while agomelatine and vortioxetine present a lower risk. Additional studies are needed to corroborate our results.
BACKGROUND: While case reports and clinical trials reported withdrawal syndrome after reduction and/or discontinuation of antidepressant drugs, no large study has been conducted to compare the risk between the different antidepressants. METHODS: Using data recorded from January 1st, 1988, and December 31st, 2020 in VigiBase®, the World Health Organization's Global Individual Case Safety Reports database, we performed disproportionality analysis to investigate the risk of reporting withdrawal syndrome in patients treated by short half-life antidepressants compared with patients treated by long half-life antidepressants. In addition, we aimed to better inform clinical practice by comparing 15 antidepressants for the risk of reporting withdrawal syndrome. RESULTS: Among the 338,498 reports with antidepressants of interest, we found 15,507 cases of withdrawal syndrome. Short half-lives antidepressants were associated with an increased risk of reporting a withdrawal syndrome compared to long half-life antidepressants (ROR 5.38; 95% CI 5.16-5.61). The risk was higher for 18-44 years old (ROR 6.88; 95% CI 6.17-7.62), women (ROR 1.38; 95% CI 1.33-1.43) and patients treated with Paroxetine, Desvenlafaxine, Venlafaxine and Duloxetine. LIMITATIONS: The limitations of this study stem from the case-reporting process. CONCLUSIONS: This large observational study in a real-world setting suggests that the use of short half-life antidepressants increases the risk of reporting withdrawal syndrome compared to long half-life antidepressants. Among the most common antidepressants, paroxetine and serotonin-noradrenaline reuptake inhibitors are associated with a greater risk of reporting withdrawal syndrome, while agomelatine and vortioxetine present a lower risk. Additional studies are needed to corroborate our results.