A Randomized Controlled Trial Comparing Efficacy and Safety of Antidepressant Monotherapy

Abstract

Background and objectives: The majority of mainstream antidepressants lack the promise of complete amelioration of symptoms. Other pitfalls include the latency period and side effects. These issues prompted investigations concerning the various roles of serotonin (5-HT) neurotransmissions in the etiology of depression. In this study, each study participant received vilazodone, vortioxetine, and escitalopram monotherapy for major depressive disorder (MDD) for 16 weeks. After that, the subject's scores on the Hamilton Depression Rating Scale (HDRS)-17 item version and the Montgomery Åsberg Depression Rating Scale (MADRS) were evaluated. In the study population, we kept track of the incidence of adverse events.

Methods: Ninety-six patients with MDD participated in this open-label, randomized, three-arm study. Participants were allotted into three groups according to a 1:1:1 ratio and given vilazodone (20-40 mg/day), vortioxetine (5-20 mg/day), or escitalopram (10-20 mg/day) for 16 weeks. Vortioxetine and vilazodone are test medications, with escitalopram serving as the control. After the baseline visit, follow-up appointments were scheduled every four weeks. Per-protocol (PP) and intent-to-treat (ITT) populations served as means for efficacy and safety evaluations, respectively. We prospectively registered this research in the Clinical Trial Registry, India (CTRI) (2022/07/043808).

Results: Out of the 134 patients we screened, 109 (81.34%) were eligible. Ninety-six (88.07%) of them completed the 16-week trial. In the PP population (n = 96), we analyzed efficacy. They had a mean age of 46.3 ± 6.2 years. At baseline, each group's median HDRS score was 30.0 (p = 0.964). Following 16 weeks of antidepressant therapy, these scores dropped to 15.0, 14.0, and 13.0 (p = 0.002). Baseline MADRS scores for all groups were 36.0 (p = 0.741). They had corresponding values of 20.0, 18.0, and 17.0 at 16 weeks (p < 0.001). Regarding both efficacy endpoints, the post-hoc analysis with the Bonferroni correction demonstrated statistically significant differences (p < 0.001). We performed the safety assessments within our ITT population (n = 109). Ninety-six adverse events were recorded. Nonetheless, none of them seemed serious. Still, five participants opted out because of their side effects. Vomiting and nausea were the most frequent side effects.

Conclusion: Compared to escitalopram and vilazodone, vortioxetine demonstrated a statistically significant reduction in HDRS and MADRS scores. It also had fewer and milder side effects. We recommend conducting studies involving a broader population to investigate the antidepressant effects of these medications further.

Keywords: adverse event; antidepressant drug; depressive disorder; escitalopram; hamilton depression rating scale; montgomery-asberg depression rating scale; randomized trial; serotonin dysfunction; vilazodone; vortioxetine.

Figure 1. CONSORT diagram

CONSORT: consolidated standards of reporting trials; ITT: intent-to-treat analysis; PP: per-protocol analysis

Figure 2. HDRS scores of participants at various time points of assessments

The HDRS scores for the three groups' participants are depicted through the box-whisker and jitter plots. During every visit, the Kruskal-Wallis test was applied to assess the groups collectively. HDRS: Hamilton Depression Rating Scale

Figure 3. Post-hoc analysis of the differences in HDRS scores from baseline

Changes in HDRS values from the baseline for the three groups' subjects are displayed via the box-whisker, jitter, and violin plots. The mean changes are highlighted through the red dots. The Bonferroni test was used after the Kruskal-Wallis test for the intergroup comparison. HDRS: Hamilton Depression Rating Scale

Figure 4. MADRS scores of participants at various time points of assessments

The MADRS scores for the three groups' participants are depicted through the box-whisker and jitter plots. During every visit, the Kruskal-Wallis test was applied to assess the groups collectively. MADRS, Montgomery Åsberg Depression Rating Scale

Figure 5. Post-hoc analysis of the differences in MADRS scores from baseline

Changes in MADRS values from the baseline for the three groups' subjects are displayed via the box-whisker, jitter, and violin plots. The mean changes are highlighted through the red dots. The Bonferroni test was used after the Kruskal-Wallis test for the intergroup comparison. MADRS, Montgomery Åsberg Depression Rating Scale

Figure 6. Adverse events noted in the study participants

The lower portion of the plot illustrates the three drug groups, and the upper portion describes the different types of adverse events noted by the participants. The bands between the lower and upper sections indicate all the events observed in each group. The number of adverse events associated with the three study groups correlates precisely with the bandwidths.