Εfficacy and safety of vortioxetine (Lu AA21004) in the treatment of adult patients with major depressive disorder: A systematic review and a meta‑analysis of randomized controlled trials.

Vortioxetine is a novel drug for the treatment of major depressive disorder (MDD). It has been reported that vortioxetine exhibits positive effect on the acute stage of MDD, while it can effectively prevent the recurrence of MDD during the maintenance period. Currently, the results of systematic reviews on vortioxetine are insufficient since several efficacy measures, such as the 24-Items Hamilton Rating Scale for Depression (HADRS-24) total score and other safety factors have not been evaluated. Therefore, the present study aimed to evaluate the efficacy and safety of different doses of vortioxetine on the treatment of adult patients with MDD via assessing more efficacy and safety indicators. The clinical, double-blind, parallel and randomized controlled trials (RCTs) on the effect of vortioxetine on MDD were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and clinical trial registration websites from database inception to November 2022. A total of two investigators independently screened the included references and independently evaluated their quality. The meta-analysis was performed using Revman 5.0 software. The present systematic review was registered in PROSPERO (registration no. CRD42018106343). In the present study 11 RCTs were included, with a total of 4,908 adult patients with MDD. More specifically, 1,158 patients were included in the 5-mg vortioxetine group, 736 in the 10-mg group, 298 in the 15-mg group, 864 in the 20-mg group and 1,852 in the placebo group. All 11 studies were randomized, double-blinded and parallel control trials, and all publications were evaluated as high quality. The meta-analysis results showed that patients in the 5-, 10- and 20-mg vortioxetine groups exhibited significantly higher Montgomery-Asberg Depression Rating Scale (MADRS) response (≥50%) and remission (≤10%) rates compared with the placebo group (P<0.05). The pooled analysis also revealed a statistically significant change in the total score of HADRS-24, MADRS, Sheehan Disability Scale (SDS), Clinical Global Impression Scale-Improvement (CGI-I) and HADRS-24 response rate in the 10- and 20-mg vortioxetine groups compared with the placebo group (P<0.05). However, no statistically significant changes in the total score of HADRS-24, MADRS, SDS, CGI-I and HADRS-24 response rate were obtained in the 5-mg group compared with the placebo group (P>0.05). Furthermore, the most common adverse events were nausea, hyperhidrosis, insomnia and vomiting, the incidence of which was increased with higher doses of vortioxetine. Overall, the results suggested that vortioxetine administration at doses of 5-20 mg was significantly effective and safe compared with placebo in the treatment of MDD. However, 5 mg vortioxetine displayed no difference in the HADRS-24, MADRS, SDS and CGI-I total scores, and HADRS-24 response rate. Furthermore, patient treatment with increasing vortioxetine doses was associated with good tolerance and high safety. Nevertheless, more multi-center, high-quality and long-term RCTs are still needed to support the aforementioned findings.