Table 1 Objectives and hypotheses of the study. Table stating study objectives and hypothesis in a generic way and in a drug-specific way

Primary objective

To investigate the antidepressant efficacy of the 6-week combined treatment of MDD with antidepressant plus anti-inflammatory

To investigate the antidepressant efficacy of the 6-week combined treatment of MDD with vortioxetine plus celecoxib 400 mg

Primary hypothesis

A higher efficacy and larger reduction in symptoms of depression will be observed after 6 weeks when treatment is combined (antidepressant and anti-inflammatory) in individuals with baseline inflammation

A higher efficacy and larger reduction in symptoms of depression will be observed after 6 weeks when treatment is combined (vortioxetine and celecoxib 400 mg) in individuals with baseline inflammation

Secondary objective 1

To investigate the anti-inflammatory effects of a combined treatment of MDD with antidepressant and anti-inflammatory in individuals with baseline inflammation (CRP levels > 3 mg/L) over a 6-week period

To investigate the anti-inflammatory effects of a combined treatment of MDD with vortioxetine and celecoxib 400 mg in individuals with baseline inflammation (CRP levels > 3 mg/L) over a 6-week period

Secondary hypothesis

A larger reduction of circulating levels of the inflammatory marker CRP will be observed in the group of depressed patients who are treated with antidepressant plus anti-inflammatory medication

A larger reduction of circulating levels of the inflammatory marker CRP will be observed in the group of depressed patients who are treated with vortioxetine plus celecoxib 400 mg

Secondary objective 2

To test whether there is evidence of a different effect of the combined treatment in the two inflammation strata

To test whether there is evidence of a different effect of the combined treatment with vortioxetine and celecoxib 400 mg in the two inflammation strata

Secondary objective 3

To investigate the safety of the anti-inflammatory treatment when combined with antidepressant

To investigate the safety celecoxib 400 mg treatment when combined with vortioxetine

Secondary objective 4

To investigate the effects of the antidepressant on cognition, psychosocial and workplace performance measures in MDD

To investigate the effects of vortioxetine on cognition, psychosocial and workplace performance measures in MDD