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| Sponsor: | University of California, Los Angeles |
|---|---|
| Information provided by: | University of California, Los Angeles |
| ClinicalTrials.gov Identifier: | NCT00628914 |
Purpose
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 mechanism(s) 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Major Depressive Disorder Insomnia |
Drug: escitalopram and eszopiclone Drug: Escitalopram, eszopiclone, and placebo Drug: Escitalopram |
Phase IV |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | Brain Mechanisms and Targeting Insomnia in Major Depression |
| Estimated Enrollment: | 60 |
| Study Start Date: | May 2008 |
| Estimated Study Completion Date: | February 2010 |
| Estimated Primary Completion Date: | November 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
Open label escitalopram plus eszopiclone for 8 weeks
|
Drug: escitalopram and eszopiclone
escitalopram 10mg tabs QD and eszopiclone 3 mg tabs QD for 8 weeks
Other Names:
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2
Escitalopram and eszopiclone for initial 4 weeks, then switch to escitalopram and placebo for final 4 weeks.
|
Drug: Escitalopram, eszopiclone, and placebo
Escitalopram 10mg tabs QD for 8 weeks; Eszopiclone 3mg tabs QD for initial 4 weeks then placebo tabs QD for final 4 weeks
Other Names:
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Placebo Comparator: 3
Escitalopram plus placebo for 8 weeks
|
Drug: Escitalopram
Escitalopram 10mg tabs QD and placebo tabs QD for 8 weeks
Other Name: Lexapro
|
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 mechanism(s) 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 (e.g., 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 (e.g., 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.
Eligibility| Ages Eligible for Study: | 18 Years to 64 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| United States, California | |
| Semel Institute for Neuroscience and Human Behavior at UCLA | |
| Los Angeles, California, United States, 90024 | |
| Principal Investigator: | Ian A Cook, MD | Semel Institute for Neuroscience and Human Behavior at UCLA |
More Information
| Responsible Party: | Ian A. Cook, M.D., University of California Los Angeles |
| ClinicalTrials.gov Identifier: | NCT00628914 History of Changes |
| Other Study ID Numbers: | ESRC973, 07-11-013 |
| Study First Received: | February 25, 2008 |
| Last Updated: | August 19, 2010 |
| Health Authority: | United States: Institutional Review Board |
|
Major Depressive Disorder Insomnia Escitalopram Lexapro |
Eszopiclone Lunesta Cordance |
|
Depression Depressive Disorder Depressive Disorder, Major Sleep Initiation and Maintenance Disorders Behavioral Symptoms Mood Disorders Mental Disorders Sleep Disorders, Intrinsic Dyssomnias Sleep Disorders Nervous System Diseases Dexetimide Citalopram Eszopiclone Antiparkinson Agents |
Anti-Dyskinesia Agents Central Nervous System Agents Therapeutic Uses Pharmacologic Actions Parasympatholytics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Muscarinic Antagonists Cholinergic Antagonists Cholinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Antidepressive Agents, Second-Generation Antidepressive Agents |
