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

Human Psychopharmacology

Volumn 29, Issue 6, 2014, Pages 568-577

  Ball, William A ^a   Snavely, Duane B ^a   Hargreaves, Richard J ^a   Szegedi, Armin ^a   Lines, Christopher ^a   Reines, Scott A ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

aprepitant; combination treatment; major depressive disorder; NK1; paroxetine; SSRI

Indexed keywords

APREPITANT; PAROXETINE; PLACEBO; ANTIDEPRESSANT AGENT; MORPHOLINE DERIVATIVE; NEUROKININ 1 RECEPTOR ANTAGONIST; SEROTONIN UPTAKE INHIBITOR;

ADULT; AGED; AKATHISIA; ANTIDEPRESSANT ACTIVITY; ANXIETY; APPETITE DISORDER; AREA UNDER THE CURVE; ARTICLE; ASTHENIA; BLURRED VISION; CLINICAL GLOBAL IMPRESSION SCALE; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG POTENTIATION; DRUG SAFETY; DRUG WITHDRAWAL; EJACULATION DISORDER; EVENING DOSAGE; FATIGUE; FEMALE; FLU LIKE SYNDROME; HAMILTON ANXIETY SCALE; HEADACHE; HUMAN; INSOMNIA; LIBIDO DISORDER; MAJOR CLINICAL STUDY; MAJOR DEPRESSION; MALE; MAXIMUM PLASMA CONCENTRATION; MENTAL DISEASE; MONOTHERAPY; NAUSEA; NERVOUSNESS; ORGASM DISORDER; OUTCOME ASSESSMENT; PARALLEL DESIGN; PARESTHESIA; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PSYCHOPHARMACOTHERAPY; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SOMNOLENCE; SWEATING; TINNITUS; TREMOR; UPPER RESPIRATORY TRACT INFECTION; XEROSTOMIA; CLINICAL TRIAL; DEPRESSIVE DISORDER, MAJOR; DRUG COMBINATION; PSYCHOLOGICAL RATING SCALE; TREATMENT OUTCOME;

ADULT; ANTIDEPRESSIVE AGENTS; DEPRESSIVE DISORDER, MAJOR; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; MALE; MORPHOLINES; NEUROKININ-1 RECEPTOR ANTAGONISTS; PAROXETINE; PSYCHIATRIC STATUS RATING SCALES; SEROTONIN UPTAKE INHIBITORS; TREATMENT OUTCOME;

EID: 84912141942     PISSN: 08856222     EISSN: 10991077     Source Type: Journal    
DOI: 10.1002/hup.2444     Document Type: Article

References (25)

1. Claghorn JL,. 1992. The safety and efficacy of paroxetine compared with placebo in a double-blind trial of depressed outpatients. J Clin Psychiatry 53 (Suppl): 33-35.
2. Curran MP, Robinson DM,. 2009. Aprepitant: a review of its use in the prevention of nausea and vomiting. Drugs 69: 1853-1878.
3. Davidson JR,. 2010. Major depressive disorder treatment guidelines in America and Europe. J Clin Psychiatry 71 (Suppl E1): e04.
4. Dechant KL, Clissold SP,. 1991. Paroxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness. Drugs 41: 225-253.
5. Detke MJ, Wiltse CG, Mallinckrodt CH, et al., 2004. Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Neuropsychopharmacol 14: 457-470.
6. Ebner K, Singewald N,. 2006. The role of substance P in stress and anxiety responses. Amino Acids 31: 251-272.
7. EMEND (aprepitant) capsules, for oral use [product label]. 2012. Merck & Co., Inc.: Whitehouse Station, NJ.
8. Feighner JP, Cohn JB, Fabre LF, Jr, et al., 1993. A study comparing paroxetine placebo and imipramine in depressed patients. J Affect Discord 28: 71-79.
9. Gelenberg AJ, Freeman MP, Markowitz JC,. 2010. American Psychiatric Association practice guideline for the treatment of patients with major depressive disorder. Am J Psychiatry 167 (suppl): e10.
10. Hafizi S, Chandra P, Cowen J,. 2007. Neurokinin-1 receptor antagonists as novel antidepressants: trials and tribulations. Br J Psychiatry 191: 282-284.
11. Hargreaves R, Ferreira JC, Hughes D, et al., 2011. Development of aprepitant, the first neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Ann N Y Acad Sci 1222: 40-48.
12. Holmes A, Heilig M, Rupniak NM, et al., 2003. Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders. Trends Pharmacol Sci 24: 580-588.
13. Katzman MA, Tricco AC, McIntosh D, et al., 2007. Paroxetine versus placebo and other agents for depressive disorders: a systematic review and meta-analysis. J Clin Psychiatry 68: 1845-1859.
14. Keller M, Montgomery S, Ball W, et al., 2006. Lack of efficacy of the substance P (neurokinin1 receptor) antagonist aprepitant in the treatment of major depressive disorder. Biol Psychiatry 59: 216-223.
15. Kessler RC, Berglund P, Demler O, et al., 2003. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 289: 3095-3105.
16. Kramer MS, Cutler N, Feighner J, et al., 1998. Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281: 1640-1645.
17. Kramer MS, Winokur A, Kelsey J, et al., 2004. Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression. Neuropsychopharmacology 29: 385-392.
18. Marks DM, Park MH, Ham BJ, et al., 2008. Paroxetine: safety and tolerability issues. Expert Opin Drug Saf 7: 783-794.
19. Ratti E, Bettica P, Alexander R, et al., 2013. Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies. J Psychopharmacol 27: 424-434.
20. Ruhe HG, Booij J, Weert HC, et al., 2009. Evidence why paroxetine dose escalation is not effective in major depressive disorder: a randomized controlled trial with assessment of serotonin transporter occupancy. Neuropsychopharmacology 34: 999-1010.
21. Rupniak NM,. 2002. New insights into the antidepressant actions of substance P (NK1 receptor) antagonists. Can J Physiol Pharmacol 80: 489-494.
22. Ryckmans T, Balancon L, Berton O, et al., 2002a. First dual NK(1) antagonists-serotonin reuptake inhibitors: synthesis and SAR of a new class of potential antidepressants. Bioorg Med Chem Lett 12: 261-264.
23. Ryckmans T, Berton O, Grimee R, et al., 2002b. Dual NK(1) antagonists-serotonin reuptake inhibitors as potential antidepressants. Part 2: SAR and activity of benzyloxyphenethyl piperazine derivatives. Bioorg Med Chem Lett 12: 3195-3198.
24. Santarelli L, Gobbi G, Blier P, et al., 2002. Behavioral and physiologic effects of genetic or pharmacologic inactivation of the substance P receptor (NK1). J Clin Psychiatry 63 (Suppl 11): 11-17.
25. Trist DG, Ratti E, Bye A,. 2013. Why receptor reserve matters for neurokinin1 (NK1) receptor antagonists. J Recept Signal Transduct Res 33: 333-337.