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Multicenter, randomized, double‐blind, active comparator and placebo‐controlled trial of a corticotropin‐releasing factor receptor‐1 antagonist in generalized anxiety disorder
Author(s) -
Coric Vladimir,
Feldman Howard H.,
Oren Dan A.,
Shekhar Anantha,
Pultz Joseph,
Dockens Randy C.,
Wu Xiaoling,
Gentile Kimberly A.,
Huang ShuPang,
Emison Eileen,
Delmonte Terrye,
D'Souza Bernadette B.,
Zimbroff Daniel L.,
Grebb Jack A.,
Goddard Andrew W.,
Stock Elyse G.
Publication year - 2010
Publication title -
depression and anxiety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.634
H-Index - 129
eISSN - 1520-6394
pISSN - 1091-4269
DOI - 10.1002/da.20695
Subject(s) - antagonist , anxiety , placebo , psychology , clinical psychology , medicine , psychiatry , pharmacology , receptor , alternative medicine , pathology
Abstract Background: Antagonism of corticotropin‐releasing factor (CRF) receptors has been hypothesized as a potential target for the development of novel anxiolytics. This study was designed to determine the safety and efficacy of pexacerfont, a selective CRF‐1 receptor antagonist, in the treatment of generalized anxiety disorder (GAD). Method: This was a multicenter, randomized, double‐blind, placebo‐controlled and active comparator trial. Two hundred and sixty patients were randomly assigned to pexacerfont 100 mg/day (after a 1 week loading dose of 300 mg/day), placebo or escitalopram 20 mg/day in a 2:2:1 ratio. The primary outcome was the mean change from baseline to end point (week 8) in the Hamilton Anxiety Scale total score. Results: Pexacerfont 100 mg/day did not separate from placebo on the primary outcome measure. The half‐powered active comparator arm, escitalopram 20 mg/day, demonstrated efficacy with significant separation from placebo at weeks 1, 2, 3, 6, and 8 ( P <.02). Response rates for pexacerfont, placebo, and escitalopram were 42, 42, and 53%, respectively. Genetic and psychometric rating scale data was obtained in 175 randomized subjects. There was a significant association between a single nucleotide polymorphism (SNP) of the gene encoding plexin A2 (PLXNA2‐2016) with the HAM‐A psychic subscale score for the entire cohort at baseline (FDR‐adjusted P =.015). Conclusions: Pexacerfont did not demonstrate efficacy compared to placebo for the treatment of GAD. Whether these findings are generalizable to this class of agents remains to be determined. Our preliminary genetic finding of an association between a SNP for the gene encoding plexin A2 and an anxiety phenotype in this study merits further exploration. The trial was registered at clinicaltrials.gov (NCT00481325) before enrollment. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.