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V1b receptor antagonist for use in the treatment of patients having an elevated avp level and/or an elevated copeptin level

Inactive Publication Date: 2015-06-04
MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN EV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to a vasopressin receptor antagonist for the treatment of depressive symptoms and anxiety symptoms in patients showing elevated levels of arginine vasopressin (AVP) and / or copeptin. The invention is based on the discovery that patients with elevated levels of AVP and copeptin in the blood or cerebrospinal fluid respond well to treatment with a vasopressin receptor antagonist. The invention also predicts that patients with specific polymorphic variants in the AVP receptor gene have a higher likelihood of responding to treatment. The invention provides a novel approach for identifying and treating patients with depressive and anxiety symptoms.

Problems solved by technology

However, so far clinical trials have been unsuccessful.

Method used

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  • V1b receptor antagonist for use in the treatment of patients having an elevated avp level and/or an elevated copeptin level
  • V1b receptor antagonist for use in the treatment of patients having an elevated avp level and/or an elevated copeptin level
  • V1b receptor antagonist for use in the treatment of patients having an elevated avp level and/or an elevated copeptin level

Examples

Experimental program
Comparison scheme
Effect test

example 1

Sample Description

[0280]Patients participating in the Munich Antidepressant Response Signature (MARS) project have been included. Selection criteria were:

[0281]150 inpatients suffering from unipolar major depression, who were divided into 75 patients with high vs. low HPA axis dysregulations, each, using matched extremes according to the results of a combined dex / CRH test at the time of admission 123 inpatients with two consecutive dex / CRH tests during hospitalisation, the first at admission, the second on average 60 days thereafter

[0282]Due to partial overlap between patients selected according to the two criteria, the total number of subjects included in this analysis is 202. Copeptin was measured in the plasma samples of the combined dex / CRH test using the first specimen, which was obtained under dex suppression, but prior to CRH stimulation.

Associations Between Copeptin and Dex / CRH Test Outcome

[0283]Patients of the MARS project have been divided into 75 with high and 75 with low...

example 2

[0290]Genetic polymorphisms that influence the extent of the ACTH response in the combined Dex / CRH test in patients with current moderate to severe depression were identified using genome-wide SNP analysis of epistasis with genetic variation in the AVPR1B gene, a key player in the pathways relating to the combined Dex / CRH test. These polymorphisms describe genetic variations that in interaction with genetic variation in the AVPR1B gene lead to major depression with CRH hyperdrive. Patients carrying the alleles / genotypes associated with a larger cortisol or ACTH response in the dex / CRH test should therefore profit from V1B antagonist treatment of depression and anxiety.

Patients:

[0291]Patients with unipolar or bipolar depression admitted as inpatients to the Max Planck Institute of Psychiatry (MPI), Munich, Germany, for treatment of a depressive episode were included in the study. Patients were diagnosed by psychiatrists according to the Diagnostic and Statistical Manual of Mental Dis...

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Abstract

The present invention relates to a vasopressin receptor 1B (V1B) antagonist for use in the treatment of depressive symptoms and / or anxiety symptoms in patients showing an elevated arginine vasopressin (AVP) level and / or an elevated copeptin level. The present invention further relates to a method for predicting the treatment response to a V1B antagonist in patients with depressive symptoms and / or anxiety symptoms.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a vasopressin receptor 1B (V1B) antagonist for use in the treatment of depressive symptoms and / or anxiety symptoms in patients showing an elevated arginine vasopressin (AVP) level and / or an elevated copeptin level. The present invention further relates to methods for predicting a treatment response to a V1B antagonist in patients with depressive symptoms and / or anxiety symptoms.BACKGROUND OF THE INVENTION[0002]Hypotheses as to the development of depression and anxiety disorders inter alia point to the role of neuropeptides, which are involved in the central regulation of stress hormones. Besides corticotropin releasing hormone, vasopressin may also play an important role in this respect (Griebel and Holsboer (2012); Neuropeptide receptor ligands as drugs for psychiatric diseases: the end of the beginning?; Nat Rev Drug Discov 11: 462-479).[0003]Vasopressin (also referred to as arginine vasopressin (AVP), vasopressin argipr...

Claims

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Application Information

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IPC IPC(8): A61K31/405C12Q1/68A61K45/06
CPCA61K31/405A61K45/06C12Q2600/106C12Q2600/156C12Q1/6883A61K31/404A61K31/573G01N2800/048G01N2800/301G01N2800/304G01N2800/52C07K14/723G01N33/57407G01N33/57434G01N33/68G01N33/6893A61P25/00A61P25/22A61P25/24A61P43/00A61K2300/00
Inventor HOLSBOER, FLORIAN
Owner MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN EV
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