Please use this identifier to cite or link to this item:
https://doi.org/10.1177/0269881113480990
DC Field | Value | |
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dc.title | Full central neurokinin-1 receptor blockade is required for efficacy in depression: Evidence from orvepitant clinical studies | |
dc.contributor.author | Ratti, E. | |
dc.contributor.author | Bettica, P. | |
dc.contributor.author | Alexander, R. | |
dc.contributor.author | Archer, G. | |
dc.contributor.author | Carpenter, D. | |
dc.contributor.author | Evoniuk, G. | |
dc.contributor.author | Gomeni, R. | |
dc.contributor.author | Lawson, E. | |
dc.contributor.author | Lopez, M. | |
dc.contributor.author | Millns, H. | |
dc.contributor.author | Rabiner, E.A. | |
dc.contributor.author | Trist, D. | |
dc.contributor.author | Trower, M. | |
dc.contributor.author | Zamuner, S. | |
dc.contributor.author | Krishnan, R. | |
dc.contributor.author | Fava, M. | |
dc.date.accessioned | 2014-11-26T09:04:09Z | |
dc.date.available | 2014-11-26T09:04:09Z | |
dc.date.issued | 2013-05 | |
dc.identifier.citation | Ratti, E., Bettica, P., Alexander, R., Archer, G., Carpenter, D., Evoniuk, G., Gomeni, R., Lawson, E., Lopez, M., Millns, H., Rabiner, E.A., Trist, D., Trower, M., Zamuner, S., Krishnan, R., Fava, M. (2013-05). Full central neurokinin-1 receptor blockade is required for efficacy in depression: Evidence from orvepitant clinical studies. Journal of Psychopharmacology 27 (5) : 424-434. ScholarBank@NUS Repository. https://doi.org/10.1177/0269881113480990 | |
dc.identifier.issn | 02698811 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/110538 | |
dc.description.abstract | Full, persistent blockade of central neurokinin-1 (NK1) receptors may be a potential antidepressant mechanism. The selective NK1 antagonist orvepitant (GW823296) was used to test this hypothesis. A preliminary positron emission tomography study in eight male volunteers drove dose selection for two randomized six week studies in patients with major depressive disorder (MDD). Displacement of central [11C]GR205171 binding indicated that oral orvepitant doses of 30-60 mg/day provided >99% receptor occupancy for ≥24 h. Studies 733 and 833 randomized patients with MDD and 17-item Hamilton Depression Rating Scale (HAM-D)≥22 to double-blind treatment with orvepitant 30 mg/day, orvepitant 60 mg/day or placebo (1:1:1). Primary outcome measure was change from baseline in 17-item HAM-D total score at Week 6 analyzed using mixed models repeated measures. Study 733 (n=328) demonstrated efficacy on the primary endpoint (estimated drug-placebo differences of 30 mg: -2.41, 95% confidence interval (CI) (-4.50 to -0.31) p=0.0245; 60 mg: -2.86, 95% CI (-4.97 to -0.75) p=0.0082). Study 833 (n=345) did not show significance (estimated drug-placebo differences of 30 mg: -1.67, 95% CI (-3.73 to 0.39) p=0.1122; 60 mg: -0.76, 95% CI (-2.85 to 1.32) p=0.4713). The results support the hypothesis that full, long lasting blockade of central NK1 receptors may be an efficacious mechanism for the treatment of MDD. © The Author(s) 2013. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1177/0269881113480990 | |
dc.source | Scopus | |
dc.subject | clinical trials | |
dc.subject | Depression | |
dc.subject | neurokinin | |
dc.subject | receptor occupancy | |
dc.subject | substance P | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE | |
dc.description.doi | 10.1177/0269881113480990 | |
dc.description.sourcetitle | Journal of Psychopharmacology | |
dc.description.volume | 27 | |
dc.description.issue | 5 | |
dc.description.page | 424-434 | |
dc.description.coden | JOPSE | |
dc.identifier.isiut | 000319010100003 | |
Appears in Collections: | Staff Publications |
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