Risk of Thrombocytopenia by SSRIs or SNRIs in Patients With Depression Based on MID-NET: A Cohort Study in Japan

Risk assessment on thrombocytopenia by selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs) is limited. An observational study with cohort design was conducted based on the MID-NET for evaluating the risk of thrombocytopenia by SSRIs and SNRIs in patients with depression compared to paroxetine. The exposure group was categorized as each drug of SSRIs/SNRIs, SSRIs group (escitalopram, sertraline, fluvoxamine), SNRIs group (duloxetine, venlafaxine, milnacipran), or vortioxetine. We estimated the adjusted hazard ratio (aHR) of each drug compared to paroxetine for the risk of thrombocytopenia (platelet count < 100,000/mm³). More severe definitions were used in sensitivity analyses. In all, 4759 patients (median age: 49 years; 31.6% male) on SSRIs, 3440 patients (62 years; 38.6% male) on SNRIs, 12 patients (42.5 years; less than 83.4% male) on vortioxetine, and 2196 patients on paroxetine (62 years; 33.2% male) were included for analysis. Compared with paroxetine, the aHRs (95% confidence interval) of SSRIs group and SNRIs group were 1.14 (0.76-1.70) and 0.77 (0.48-1.21), respectively. Among SSRIs, sertraline and fluvoxamine showed a relatively higher point estimate of aHR > 1.0 (1.23 [95% confidence interval: 0.78-1.94] and 1.48 [0.87-2.51], respectively). The consistent results were also observed in the sensitivity analyses. The results suggest that the risk of thrombocytopenia by sertraline or fluvoxamine was comparable to that by paroxetine, known as having the risk of thrombocytopenia, leading to the revision of the sertraline package insert as a regulatory safety measure. Prescribers and clinicians may need to be vigilant to the possibility of sertraline-induced thrombocytopenia in clinical practice.