Safety and tolerability of vortioxetine versus serotonin reuptake inhibitors in late life depression: A systematic review and meta-analysis.

Introduction: Late-life depression (LLD) is a significant yet often under-recognized health concern. While selective serotonin reuptake inhibitors (SSRIs) are widely used, their adverse effects remain a challenge. Vortioxetine, a multimodal antidepressant, has gained attention for its potentially better tolerability. However, data on its safety in older adults are limited. This meta-analysis assessed the safety and tolerability of Vortioxetine compared to serotonin reuptake inhibitors in LLD.

Methods: A systematic search of PubMed, EMBASE, and Cochrane Central identified randomized controlled trials (RCTs) evaluating Vortioxetine's safety in ≥ 60-year-old patients. Primary outcomes included adverse events and withdrawal rates. Statistical analyses were conducted using Review Manager.

Results: Three studies, involving 714 patients were included. There were no statistical differences between groups for nausea (RR 0.54; 95 % CI 0.22, 1.34; p = 0.18; I2 =75 %), diarrhea (RR 0.92; 95 % CI 0.20, 4.13; p = 0.91; I2 =59 %), constipation (RR 0.54; 95 % CI 0.28,1.02; p = 0.06; I2 =0 %) and loss of appetite (RR 1.00; 95 % CI 0.25, 4.05; p = 1.00; I2 =40 %). The total number of dropouts after randomization did not show a statistical significance with Vortioxetine use (RR 1.10; CI 95 % 0.82, 1.48; p = 0.52; I2 = 0 %), nor did the number of withdrawals (RR 1.09, CI 95 % 0.77, 1.55; p = 0.64; I2 = 0 %).

Conclusion: This meta-analysis suggests Vortioxetine is safe for LLD, with no significant increase in adverse effects. While reassuring, these findings emphasize the need for careful evaluation, as Vortioxetine showed no clear tolerability advantage over other serotonin reuptake inhibitors.