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Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression
Authors
Kramer, Mark S.Winokur, Andrew
Kelsey, Jeffrey
Preskorn, Sheldon H.
Rothschild, Anthony J.
Snavely, Duane
Ghosh, Kalyan
Ball, William A.
Reines, Scott A.
Munjack, Dennis
Apter, Jeffrey T.
Cunningham, Lynn
Kling, Mitchel
Bari, Mohammed
Getson, Albert
Lee, Yih
UMass Chan Affiliations
Department of PsychiatryDocument Type
Journal ArticlePublication Date
2003-12-11Keywords
AdolescentAdult
Antidepressive Agents
Depressive Disorder, Major
Double-Blind Method
*Drug Evaluation
Drug Tolerance
Female
Humans
Male
Middle Aged
Personality Inventory
Psychiatric Status Rating Scales
Receptors, Neurokinin-1
Time Factors
Treatment Outcome
Psychiatry
Metadata
Show full item recordAbstract
The efficacy and safety of a selective NK(1) antagonist, L-759274, was investigated in outpatients with diagnosis of major depressive disorder with melancholic features, following evidence obtained with the novel compound aprepitant that Substance P (NK(1)) antagonists may provide a unique mechanism of antidepressant activity. A randomized, double-blind placebo-controlled study was carried out. Patients, male or female, aged 18-60, scoring >/=25 points on total of first 17 items of 21-item Hamilton Depression Scale (HAMD), and scoring >/=4 (moderately ill) on Clinical Global Impressions-Severity Scale were randomized to oral L-759274 40 mg daily (n=66) or placebo (n=62) for 6 weeks. For patients receiving L-759274, improvement (mean decrease from baseline) in HAMD-17 total score was 10.7 points, compared with a mean 7.8 point improvement in patients receiving placebo (p<0.009). Mean scores for item 1 of HAMD-17 (depressed mood) also improved to a greater extent in the active group compared with the placebo group (0.3 points, p<0.058). Compared with placebo, mean scores on Clinical Global Impressions-Improvement Scale improved significantly by the end of the trial (p=0.009). L-759274 was generally safe and well-tolerated. The incidence of sexual side effects was on par with that observed in patients receiving placebo, and the incidences of gastrointestinal effects were low. Antidepressant actions have now been observed with two different highly selective NK(1) antagonists (aprepitant and L-759274). NK(1) antagonism is a replicated and generally well-tolerated antidepressant mechanism.Source
Neuropsychopharmacology. 2004 Feb;29(2):385-92. Link to article on publisher's siteDOI
10.1038/sj.npp.1300260Permanent Link to this Item
http://hdl.handle.net/20.500.14038/46059PubMed ID
14666114Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/sj.npp.1300260