Addition of an NK1receptor 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

Objective Aprepitant 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. Methods Outpatients with major depressive disorder were randomized to aprepitant 200 mg + paroxetine 20 mg, paroxetine + placebo, or aprepitant + placebo for 6 weeks. 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. Results A 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. Conclusion Concomitant use of aprepitant + paroxetine for 6 weeks did not provide greater antidepressant benefit compared with paroxetine + placebo in patients with major depression. Copyright © 2014 John Wiley & Sons, Ltd.