Addition of an NK1 receptor antagonist to an SSRI did not enhance the antidepressant effects of SSRI monotherapy: results from a randomized clinical trial in patients with major depressive disorder

ObjectiveAprepitant is a neurokinin 1 receptor antagonist approved for prevention of chemotherapy-induced and post-operative nausea and vomiting. Early studies demonstrated promising antidepressant activity as monotherapy, although this was unsupported by subsequent phase 3 trials. This phase 2 study evaluated whether aprepitant potentiated the antidepressant effects of paroxetine. MethodsOutpatients with major depressive disorder were randomized to aprepitant 200mg+paroxetine 20mg, paroxetine+placebo, or aprepitant+placebo for 6weeks. The primary endpoint was change in HAMD-17 total score. Secondary/exploratory endpoints included changes in HAMA, CGI-S, CGI-I, and HAMD Item-1 scores at week 6. ResultsA total of 79, 78, and 79 patients received aprepitant+paroxetine, paroxetine+placebo, and aprepitant+placebo, respectively. At week 6, mean changes in HAMD-17 were -11.0 (95% confidence interval [CI]: -12.7, -9.4), -11.7 (95% CI: -13.3, -10.0), and -9.5 (95% CI: -10.9, -8.1), respectively. Pairwise comparisons of HAMD-17 change with combination therapy versus paroxetine alone demonstrated no significant difference (p=0.567). Changes in CGI-S, CGI-I, and HAMD Item-1 scores were also comparable, although there was a greater reduction in anxiety (HAMA) with paroxetine alone than aprepitant+paroxetine (p=0.045). Adverse events were generally more common with the combination than either monotherapy. ConclusionConcomitant use of aprepitant+paroxetine for 6weeks did not provide greater antidepressant benefit compared with paroxetine+placebo in patients with major depression. Copyright (c) 2014 John Wiley & Sons, Ltd.