title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  Concomitant use of aprepitant + paroxetine for 6 weeks did not provide greater antidepressant benefit compared with paroxetine + placebo in patients with major depression.
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Ball
authors.forename: Duane B
authors.initials: DB
authors.lastname: Snavely
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hargreaves
authors.forename: Armin
authors.initials: A
authors.lastname: Szegedi
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.forename: Scott A
authors.initials: SA
authors.lastname: Reines
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077608:Aprepitant; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009025:Morpholines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D064729:Neurokinin-1 Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017374:Paroxetine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D000077608:Aprepitant; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: NK1; SSRI; aprepitant; combination treatment; major depressive disorder; paroxetine