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An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder.
J Clin Psychopharmacol 2008; 28(6):631-7JC

Abstract

This randomized, placebo-controlled, double-blind study was the first to evaluate the antidepressant efficacy, safety, and tolerability of an NR2B subunit-selective N-methyl-D-aspartate receptor antagonist, CP-101,606. Subjects had major depression, according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and a history of treatment refractoriness to least 1 adequate trial of a selective serotonin reuptake inhibitor. The study had 2 treatment periods. In period 1, subjects first received a 6-week open-label trial of paroxetine and a single-blind, intravenous placebo infusion. Period 1 nonresponders (n = 30) then received a randomized double-blind single infusion of CP-101,606 or placebo plus continued treatment with paroxetine for up to an additional 4 weeks (period 2). Depression severity was assessed using the Montgomery-Asberg Depression Rating Scale and 17-item Hamilton Depression Rating Scale. On the prespecified main outcome measure (change from baseline in the Montgomery-Asberg Depression Rating Scale total score at day 5 of period 2), CP-101,606 produced a greater decrease than did placebo (mean difference, 8.6; 80% confidence interval, -12.3 to -4.5) (P < 0.10). Hamilton Depression Rating Scale response rate was 60% for CP-101,606 versus 20% for placebo. Seventy-eight percent of CP-101,606-treated responders maintained response status for at least 1 week after the infusion. CP-101,606 was safe, generally well tolerated, and capable of producing an antidepressant response without also producing a dissociative reaction. Antagonism of the NR2B subtype of the N-methyl-D-aspartate receptor may be a fruitful target for the development of a new antidepressant with more robust effects and a faster onset compared with those currently available and capable of working when existing antidepressants do not.

Authors+Show Affiliations

Clinical Research Institute, Wichita, KS 67204, USA. spreskorn@cri-research.netNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19011431

Citation

Preskorn, Sheldon H., et al. "An Innovative Design to Establish Proof of Concept of the Antidepressant Effects of the NR2B Subunit Selective N-methyl-D-aspartate Antagonist, CP-101,606, in Patients With Treatment-refractory Major Depressive Disorder." Journal of Clinical Psychopharmacology, vol. 28, no. 6, 2008, pp. 631-7.
Preskorn SH, Baker B, Kolluri S, et al. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. J Clin Psychopharmacol. 2008;28(6):631-7.
Preskorn, S. H., Baker, B., Kolluri, S., Menniti, F. S., Krams, M., & Landen, J. W. (2008). An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. Journal of Clinical Psychopharmacology, 28(6), pp. 631-7. doi:10.1097/JCP.0b013e31818a6cea.
Preskorn SH, et al. An Innovative Design to Establish Proof of Concept of the Antidepressant Effects of the NR2B Subunit Selective N-methyl-D-aspartate Antagonist, CP-101,606, in Patients With Treatment-refractory Major Depressive Disorder. J Clin Psychopharmacol. 2008;28(6):631-7. PubMed PMID: 19011431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. AU - Preskorn,Sheldon H, AU - Baker,Bryan, AU - Kolluri,Sheela, AU - Menniti,Frank S, AU - Krams,Michael, AU - Landen,Jaren W, PY - 2008/11/18/pubmed PY - 2009/2/3/medline PY - 2008/11/18/entrez SP - 631 EP - 7 JF - Journal of clinical psychopharmacology JO - J Clin Psychopharmacol VL - 28 IS - 6 N2 - This randomized, placebo-controlled, double-blind study was the first to evaluate the antidepressant efficacy, safety, and tolerability of an NR2B subunit-selective N-methyl-D-aspartate receptor antagonist, CP-101,606. Subjects had major depression, according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and a history of treatment refractoriness to least 1 adequate trial of a selective serotonin reuptake inhibitor. The study had 2 treatment periods. In period 1, subjects first received a 6-week open-label trial of paroxetine and a single-blind, intravenous placebo infusion. Period 1 nonresponders (n = 30) then received a randomized double-blind single infusion of CP-101,606 or placebo plus continued treatment with paroxetine for up to an additional 4 weeks (period 2). Depression severity was assessed using the Montgomery-Asberg Depression Rating Scale and 17-item Hamilton Depression Rating Scale. On the prespecified main outcome measure (change from baseline in the Montgomery-Asberg Depression Rating Scale total score at day 5 of period 2), CP-101,606 produced a greater decrease than did placebo (mean difference, 8.6; 80% confidence interval, -12.3 to -4.5) (P < 0.10). Hamilton Depression Rating Scale response rate was 60% for CP-101,606 versus 20% for placebo. Seventy-eight percent of CP-101,606-treated responders maintained response status for at least 1 week after the infusion. CP-101,606 was safe, generally well tolerated, and capable of producing an antidepressant response without also producing a dissociative reaction. Antagonism of the NR2B subtype of the N-methyl-D-aspartate receptor may be a fruitful target for the development of a new antidepressant with more robust effects and a faster onset compared with those currently available and capable of working when existing antidepressants do not. SN - 1533-712X UR - https://www.unboundmedicine.com/medline/citation/19011431/An_innovative_design_to_establish_proof_of_concept_of_the_antidepressant_effects_of_the_NR2B_subunit_selective_N_methyl_D_aspartate_antagonist_CP_101606_in_patients_with_treatment_refractory_major_depressive_disorder_ L2 - http://Insights.ovid.com/pubmed?pmid=19011431 DB - PRIME DP - Unbound Medicine ER -