Vortioxetin (1) – Brintellix®

• Clinical trials
  • The LuAA21004_318 trial comprises a randomised, double-blind, head-to-head comparison between vortioxetine and the SSRI escitalopram.

a) Mild episode of major depression

• The additional benefit is not proven.
• According to the generally accepted state of medical knowledge, pharmacological intervention is not usually medically indicated for the condition ‘mild episode of major depression’.
• As these patients were not included in the studies presented, no data are available to assess the additional benefit of vortioxetine in mild episodes of major depression.

b) Moderate episode of major depression

• The additional benefit is not proven.
• To demonstrate additional benefit in moderate and severe episodes of major depression compared with an appropriate comparator therapy, the pharmaceutical manufacturer selected the active ingredient citalopram from the SSRI class.
• Due to the methodologically unclear approach taken in the selection of studies for the indirect comparison, the analyses submitted by the pharmaceutical manufacturer cannot be used to establish any additional benefit of vortioxetine compared with citalopram.
• Overall, therefore, the additional benefit for the entire course of treatment of an episode of major depression is not proven.

c) Severe episode of major depression

• An additional benefit is not proven.
• To demonstrate additional benefit in moderate and severe episodes of major depression compared with an appropriate comparator therapy, the pharmaceutical manufacturer selected the active ingredient citalopram from the SSRI class.
• Due to the methodologically unclear approach taken in the selection of studies for the indirect comparison, the analyses submitted by the pharmaceutical manufacturer cannot be used to establish any additional benefit of vortioxetine compared with citalopram.
• Overall, therefore, the additional benefit for the entire course of treatment of an episode of major depression is not proven.
• Side effects – Sexual dysfunction
  • The study shows no clinically relevant differences between vortioxetine and escitalopram with regard to sexual dysfunction.
  • However, the continuous data from the CSFQ-14 (Sexual Functioning Questionnaire Short-Form) reveal a statistically significant difference between the treatment groups (between-group difference in the mean change from baseline to week 8 in the total score: 2.2; 95% CI [0.48–4.02], p = 0.013).
  • However, an assessment of the effect size based on Hedges’ g does not suggest that the effect is clinically relevant, as the 95% confidence interval does not lie entirely above the irrelevance threshold of 0.2 (standardised mean difference 0.26, 95% CI [0.5–0.48], p = 0.016).
  • Responder analyses of patients who did not report sexual dysfunction at the end of the study (OR 1.37; 95% CI [0.93–2.03]; p = 0.112) or of patients who showed a pre-specified improvement in the total score of ≥ 3 points, defined by the pU as relevant (OR 1.50; 95% CI [0.99–2.29]; p = 0.057) showed no statistically significant difference between the treatment groups.
  • The LuAA21004_318 study therefore provides no overall hints of additional benefit, in particular no hints of additional benefit from vortioxetine in relation to the sexual side effects of antidepressant treatment with SSRIs.

Courtesy translation only, please refer to the German original.