Ignite Creation Date:
2024-05-05 @ 7:13 PM
Last Modification Date:
2024-10-26 @ 9:45 AM
Study NCT ID:
NCT00628914
Status:
UNKNOWN
Last Update Posted:
2010-08-20
First Post:
2008-02-25
Brief Title:
Brain Mechanisms and Targeting Insomnia in Major Depression
Sponsor:
University of California Los Angeles
Organization:
University of California Los Angeles
Study Overview
Official Title:
Brain Mechanisms and Targeting Insomnia in Major Depression
Status:
UNKNOWN
Status Verified Date:
2010-07
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Preliminary studies suggest that the response to antidepressant medication can be accelerated by targeting insomnia with adjunctive use of eszopiclone It is not yet known what mechanisms support this acceleration in response though preliminary findings support the hypothesis that early restoration of sleep may facilitate BDNF-based effects of antidepressant medications The optimal duration of co-treatment is also unknown This study will test specific hypotheses about brain mechanisms and evaluate the effects of continued eszopiclone beyond the time window when response acceleration should be observed
Detailed Description:
A critical challenge in the management of major depressive disorder MDD is the delay between initiating treatment with an antidepressant medication and clinical improvement Preliminary studies Fava et al 2006 Krystal et al 2007 suggest that targeting insomnia with eszopiclone ESZ in patients receiving fluoxetine may lead to more rapid resolution of symptoms Studies have not yet been able to differentiate between competing explanations of this phenomenon whether co-treatment with ESZ actually accelerates changes in the brain associated with antidepressant treatment response or if its effects on the insomnia component are confined to the symptomatic level masking As a non-benzodiazepine GABA-receptor agonist with FDA approval for long-term use in the treatment of sleep disturbances ESZ is an appropriate agent for targeting insomnia in MDD without major concerns around the development of tolerance Further research in co-treatment would be advanced by understanding the mechanisms underlying accelerated improvement
Our prior work Cook et al 2001 2002 2005 Leuchter et al 2002 has studied a new physiologic biomarker of response to SSRI and mixed-action antidepressants The EEG-based cordance biomarker can detect the physiologic effects of successful antidepressant treatment at 48 hours 1 week and 2 weeks of treatment in contrast symptom differences between responders and non-responders did not separate until 4 weeks of treatment in our placebo-controlled trials Additionally the magnitude of early physiologic change was associated with the completeness of clinical response Our biomarker has been independently studied and our findings replicated Bareš et al 2007 The cordance biomarker can be considered as a leading indicator or predictor of treatment outcome As a non-invasive probe of brain physiology it may detect early neurophysiologic changes associated with accelerated clinical response from eszopiclone
Other research has reported that brain derived neurotrophic factor BDNF is reduced in many patients with MDD Karege et al 2002 2005 Shimizu et al 2003 and may rise during the course of treatment with antidepressant medication eg Gonul et al 2005 Yoshimura et al 2007 Huang et al 2007 BDNF-related neuroplasticity has been suggested as a mechanism by which medications can lead to mood improvement Duman 2002 Manji et al 2003 Sleep patterns have also been shown to have an impact on neuroplasticity Taishi et al 2001 cf Benington Frank 2003 A simple acute phase-shift in sleep can impact BDNF levels Sei 2003 suggesting that a link between sleep and symptomatic recovery from depression might operate via a BDNF mechanism and reflect changes in brain physiology
While Krystal and colleagues 2007 previously reported that the beneficial clinical effects of 8 weeks of co-treatment did not diminish significantly in the two weeks following ESZ discontinuation controlled studies have not examined outcomes in clinically-likely scenarios employing shorter co-treatment periods eg 4 weeks during which much of the acceleration occurs
Based on these previous studies this study will assess patients with MDD during treatment with an SSRI antidepressant escitalopram ESC administered along with either ESZ or placebo PBO using a clinical symptom ratings b serum levels of BDNF c cognitive function and d brain physiology with EEG
Our prior work Cook et al 2001 2002 2005 Leuchter et al 2002 has studied a new physiologic biomarker of response to SSRI and mixed-action antidepressants The EEG-based cordance biomarker can detect the physiologic effects of successful antidepressant treatment at 48 hours 1 week and 2 weeks of treatment in contrast symptom differences between responders and non-responders did not separate until 4 weeks of treatment in our placebo-controlled trials Additionally the magnitude of early physiologic change was associated with the completeness of clinical response Our biomarker has been independently studied and our findings replicated Bareš et al 2007 The cordance biomarker can be considered as a leading indicator or predictor of treatment outcome As a non-invasive probe of brain physiology it may detect early neurophysiologic changes associated with accelerated clinical response from eszopiclone
Other research has reported that brain derived neurotrophic factor BDNF is reduced in many patients with MDD Karege et al 2002 2005 Shimizu et al 2003 and may rise during the course of treatment with antidepressant medication eg Gonul et al 2005 Yoshimura et al 2007 Huang et al 2007 BDNF-related neuroplasticity has been suggested as a mechanism by which medications can lead to mood improvement Duman 2002 Manji et al 2003 Sleep patterns have also been shown to have an impact on neuroplasticity Taishi et al 2001 cf Benington Frank 2003 A simple acute phase-shift in sleep can impact BDNF levels Sei 2003 suggesting that a link between sleep and symptomatic recovery from depression might operate via a BDNF mechanism and reflect changes in brain physiology
While Krystal and colleagues 2007 previously reported that the beneficial clinical effects of 8 weeks of co-treatment did not diminish significantly in the two weeks following ESZ discontinuation controlled studies have not examined outcomes in clinically-likely scenarios employing shorter co-treatment periods eg 4 weeks during which much of the acceleration occurs
Based on these previous studies this study will assess patients with MDD during treatment with an SSRI antidepressant escitalopram ESC administered along with either ESZ or placebo PBO using a clinical symptom ratings b serum levels of BDNF c cognitive function and d brain physiology with EEG
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 07-11-013 | None | None | None |