Comparative effects of 15 antidepressants on the risk of withdrawal syndrome: A real-world study using the WHO pharmacovigilance database

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.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.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.The limitations of this study stem from the case-reporting process.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.