Major Depressive Disorder (MDD)Phase 1NCT07139834
Pattern Separation in Major Depressive Disorder
A Phase 1 study testing SSRI (escitalopram or sertraline) and Extended-Release Memantine in people with Major Depressive Disorder (MDD), run by Jeffrey Miller at 1 site in United States.
Trial summary
This study seeks to examine the effects of treatment with a selective serotonin reuptake inhibitor (SSRI), escitalopram, a first-line treatment for depression, in combination with placebo or with extended-release memantine, on neuropsychological function, regional brain activity assessed by functional magnetic… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Major Depressive Disorder (MDD)
- What is being tested?
- SSRI (escitalopram or sertraline) and Extended-Release Memantine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2026to 30 Jun 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18-50
- Current diagnosis of MDD without psychotic features assessed within three weeks of study enrollment
- 17-item Hamilton Depression Rating Scale score ≥17 assessed within 3 weeks of study enrollment
- Using an effective form of contraception at study enrollment and agrees to continue throughout study participation for individuals of child-bearing potential
- Capacity to provide informed consent
- Proficient in English
- Willing to provide emergency contact
Who cannot join
- Currently taking an antidepressant medication at study enrollment
- Pregnant or breastfeeding at time of enrollment
- Evidence of current unstable medical illness, including liver or renal impairment, or unstable cardiovascular or respiratory illness
- QTc interval greater than 500 ms
- Current genitourinary conditions that raise urine pH such as a) renal tubular acidosis or b) severe infection of the urinary tract.
- Clinically significant neurological conditions, including a) history of stroke, b) previous head injury with evidence of cognitive impairment, c) history of malignancy or d) history of seizure disorder. (headache, migraines, pain disorders, and other conditions not exclusionary)
Show all 18Show fewer
- Lifetime diagnosis of a) bipolar disorder, b) psychotic disorder, or c) dementia
- Current active suicidal ideation
- Current substance use disorder other than tobacco use disorder
- Current or recent (past 6 months) treatment with antipsychotics; current or recent (past 1 month) treatment with benzodiazepines; current use of prescribed stimulant medication; current use of other NMDA antagonists (amantadine, ketamine, dextromethorphan)
- Current use of disulfiram with oral concentrate, MAOIs (including linezolid or IV methylene blue), or pimozide
- History of hypersensitivity or allergic reaction to a) memantine hydrochloride or any of its components/excipients, b) citalopram, escitalopram, or any other component of the product, or c) sertraline or any other component of the product
- Concurrent or recent (past 6 months) participation in another clinical trial for mental illness involving an investigational product or device
- Lack of response to or intolerable side-effects from trials of two or more selective serotonin reuptake inhibitors of adequate dose and duration at study enrollment
- Electroconvulsive therapy (ECT) in the past 6 months
- Any condition or material in the body that is a contraindication for MRI procedures
- Weight that exceeds 300 lbs or inability to fit into MRI scanner
- MST LDI score greater than 0.5
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Abigail Byrnes contact
United States1 site, 1 recruiting
- Recruiting
New York State Psychiatric Institute (NYSPI)
New York, New York, 10032
Jeffrey M Miller, MD, 646-774-7613, HDRFstudy@nyspi.columbia.edu
Abigail Byrnes, BA, HDRFstudy@nyspi.columbia.edu
About this study
Official title: Examining the Effects of Escitalopram and Memantine on Pattern Separation in Major Depressive Disorder
This study seeks to examine the effects of treatment with a selective serotonin reuptake inhibitor (SSRI), escitalopram, a first-line treatment for depression, in combination with placebo or with extended-release memantine, on neuropsychological function, regional brain activity assessed by functional magnetic resonance imaging, and depressive symptoms, in participants with Major Depressive Disorder. Escitalopram is administered in an open-label fashion in this study; extended release memantine is administered in a double-blind, randomized, placebo-controlled manner.
Read the detailed description
Pattern separation is the process of separating overlapping sensory information, contexts, or experiences into distinct neural representations. In humans, deficits in pattern separation are believed to underlie overgeneralization seen in depression and post-traumatic stress disorder (PTSD). Cross-sectional data support the effects of SSRI medications on pattern separation. Specifically, a recent paper demonstrated patients with depression who responded to SSRI medication had improved pattern separation performance (mnemonic discrimination) of emotionally neutral stimuli than SSRI non-responders, and that the findings were reversed with respect to emotionally negative stimuli (Phillips et al., 2023). These data are consistent with the negative cognitive bias in depression (Beevers et al., 2019), and provide indirect evidence of SSRI effects on pattern separation in humans. However, there is a dearth of longitudinal, within-subject analyses of SSRI effects on pattern separation performance, and associated neural activity quantified by BOLD signal from fMRI.
In the current study, we seek to examine the individual effect of SSRI treatment (in combination with placebo) as compared to the combined effect of treatment with SSRI and memantine, an NMDA-antagonist, on pattern separation, both in terms of behavioral performance and activity in the dentate gyrus as assessed by fMRI, and on depression severity. We propose to study individuals with major depressive disorder in a current major depressive episode who are currently unmedicated, who will undergo baseline medical and psychiatric assessment and fMRI scanning, followed by standardized treatment with escitalopram combined with either placebo or memantine in the context of a double-blind, placebo-controlled, randomized clinical trial.
- Conditions
- Major Depressive Disorder (MDD)
- Being tested
- SSRI (escitalopram or sertraline), Extended-Release Memantine, Placebo
- Keywords
- Depression, Major depressive disorder, MDD, Pattern separation, Memantine
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SSRI (escitalopram or sertraline)Drug
11 weeks of open-label treatment with an SSRI, of which the last 6 weeks are augmented with memantine vs placebo. Primary SSRI for the study is escitalopram. In cases of prior intolerance or non-response to escitalopram, individuals will be treated with sertraline instead of escitalopram.
Extended-Release MemantineDrug
6 weeks of treatment with extended-release memantine as augmentation to ongoing escitalopram treatment
PlaceboDrug
6 weeks of treatment with placebo as augmentation to ongoing escitalopram treatment
| Study group | Role | What they receive |
|---|---|---|
| SSRI + Memantine | Experimental | Not described Receives: Drug: SSRI (escitalopram or sertraline); Drug: Extended-Release Memantine |
| SSRI + Placebo | Placebo comparator | Not described Receives: Drug: SSRI (escitalopram or sertraline); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pattern Separation Performance
Participants will complete a pattern separation task
Measured: At baseline (week 0) and after completing the medication trial (week 11)
Secondary outcomes (1)
Depression Severity
Depression severity will be assessed using the Montgomery-Asberg Depression Rating Scale (MADRS)
Measured: At screening, baseline (week 0) and after completing the medication trial (week 11)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2025
- Study start1 Jun 2026
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Major Depressive Disorder (MDD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jeffrey Miller
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jeffrey Miller, New York State Psychiatric Institute
- Investigators
- Jeffrey M Miller, MD, Principal investigator, New York State Psychiatric Institute (NYSPI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07139834
- Sponsor's protocol ID
- 00081503
- Status last verified
- Sep 2026
- First submitted
- 15 Aug 2025
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data from this study may be shared with other investigators, including neuroimaging, neurocognitive, diagnostic, demographic, and clinical ratings data.
Publications
Beevers CG, Mullarkey MC, Dainer-Best J, Stewart RA, Labrada J, Allen JJB, McGeary JE, Shumake J. Association between negative cognitive bias and depression: A symptom-level approach. J Abnorm Psychol. 2019 Apr;128(3):212-227. doi: 10.1037/abn0000405. Epub 2019 Jan 17.
PubMed 30652884Phillips TO, Castro M, Vas RK, Ferguson LA, Harikumar A, Leal SL. Perceived antidepressant efficacy associated with reduced negative and enhanced neutral mnemonic discrimination. Front Hum Neurosci. 2023 Aug 28;17:1225836. doi: 10.3389/fnhum.2023.1225836. eCollection 2023.
PubMed 37701502
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Examining the Effects of Escitalopram and Memantine on Pattern Separation in Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT07139834
- Acronym / sponsor ID
- 00081503
- Conditions
- Major Depressive Disorder (MDD)
- Keywords
- Depression, Major depressive disorder, MDD, Pattern separation, Memantine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Jeffrey MillerUniversity, hospital or other
- Study start
- 1 Jun 2026 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 24 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study seeks to examine the effects of treatment with a selective serotonin reuptake inhibitor (SSRI), escitalopram, a first-line treatment for depression, in combination with placebo or with extended-release memantine, on neuropsychological function, regional brain activity assessed by functional magnetic resonance imaging, and depressive symptoms, in participants with Major Depressive Disorder. Escitalopram is administered in an open-label fashion in this study; extended release memantine is administered in a double-blind, randomized, placebo-controlled manner.
Detailed description
Pattern separation is the process of separating overlapping sensory information, contexts, or experiences into distinct neural representations. In humans, deficits in pattern separation are believed to underlie overgeneralization seen in depression and post-traumatic stress disorder (PTSD). Cross-sectional data support the effects of SSRI medications on pattern separation. Specifically, a recent paper demonstrated patients with depression who responded to SSRI medication had improved pattern separation performance (mnemonic discrimination) of emotionally neutral stimuli than SSRI non-responders, and that the findings were reversed with respect to emotionally negative stimuli (Phillips et al., 2023). These data are consistent with the negative cognitive bias in depression (Beevers et al., 2019), and provide indirect evidence of SSRI effects on pattern separation in humans. However, there is a dearth of longitudinal, within-subject analyses of SSRI effects on pattern separation performance, and associated neural activity quantified by BOLD signal from fMRI.
In the current study, we seek to examine the individual effect of SSRI treatment (in combination with placebo) as compared to the combined effect of treatment with SSRI and memantine, an NMDA-antagonist, on pattern separation, both in terms of behavioral performance and activity in the dentate gyrus as assessed by fMRI, and on depression severity. We propose to study individuals with major depressive disorder in a current major depressive episode who are currently unmedicated, who will undergo baseline medical and psychiatric assessment and fMRI scanning, followed by standardized treatment with escitalopram combined with either placebo or memantine in the context of a double-blind, placebo-controlled, randomized clinical trial.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SSRI + Memantine | Experimental | Drug: SSRI (escitalopram or sertraline), Drug: Extended-Release Memantine |
| SSRI + Placebo | Placebo comparator | Drug: SSRI (escitalopram or sertraline), Drug: Placebo |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Age 18-50
- Current diagnosis of MDD without psychotic features assessed within three weeks of study enrollment
- 17-item Hamilton Depression Rating Scale score ≥17 assessed within 3 weeks of study enrollment
- Using an effective form of contraception at study enrollment and agrees to continue throughout study participation for individuals of child-bearing potential
- Capacity to provide informed consent
Key exclusion criteria (18 listed)
- Currently taking an antidepressant medication at study enrollment
- Pregnant or breastfeeding at time of enrollment
- Evidence of current unstable medical illness, including liver or renal impairment, or unstable cardiovascular or respiratory illness
- QTc interval greater than 500 ms
- Current genitourinary conditions that raise urine pH such as a) renal tubular acidosis or b) severe infection of the urinary tract.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SSRI (escitalopram or sertraline)11 weeks of open-label treatment with an SSRI, of which the last 6 weeks are augmented with memantine vs placebo. Primary SSRI for the study is escitalopram. In cases of prior intolerance or non-response to escitalopram, individuals will be treated with sertraline instead of escitalopram. | Drug | SSRI + Memantine, SSRI + Placebo |
| Extended-Release Memantine6 weeks of treatment with extended-release memantine as augmentation to ongoing escitalopram treatment | Drug | SSRI + Memantine |
| Placebo6 weeks of treatment with placebo as augmentation to ongoing escitalopram treatment | Drug | SSRI + Placebo |
Primary outcome
Pattern Separation Performance
Time frame: At baseline (week 0) and after completing the medication trial (week 11)
Participants will complete a pattern separation task
1 secondary outcome
Depression Severity
Time frame: At screening, baseline (week 0) and after completing the medication trial (week 11)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Background: PubMed 30652884Beevers CG, Mullarkey MC, Dainer-Best J, Stewart RA, Labrada J, Allen JJB, McGeary JE, Shumake J. Association between negative cognitive bias and depression: A symptom-level approach. J Abnorm Psychol. 2019 Apr;128(3):212-227. doi: 10.1037/abn0000405. Epub 2019 Jan 17.
- Background: PubMed 37701502Phillips TO, Castro M, Vas RK, Ferguson LA, Harikumar A, Leal SL. Perceived antidepressant efficacy associated with reduced negative and enhanced neutral mnemonic discrimination. Front Hum Neurosci. 2023 Aug 28;17:1225836. doi: 10.3389/fnhum.2023.1225836. eCollection 2023.
- Individual participant dataSharing planned: Yes. De-identified individual participant data from this study may be shared with other investigators, including neuroimaging, neurocognitive, diagnostic, demographic, and clinical ratings data.
Related trials for Major Depressive Disorder (MDD)
Enrolling by invitationObservational study
Digital Phenotypes for Predicting Depression_Validation
Major Depressive Disorder, Bipolar I Disorder
Recruiting
Understanding the Neural Underpinnings of Risk-Taking Behavior in Psychiatric Disease
Depression - Major Depressive Disorder
RecruitingPhase 2
Cognitive Dysfunction and Inflammation in Depression: Experimental Inhibition Via Infliximab
Depressive Disorder, Major, Inflammation
RecruitingObservational study
Tracking Response to Antidepressants in Advance of Investigational Trials
Major Depressive Disorder
Not yet recruiting
Sedation and Guided Education for Depression Study
Major Depressive Disorder (MDD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Abigail Byrnes contact
Jeffrey M Miller, MD principal investigator
New York State Psychiatric Institute (NYSPI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SSRI (escitalopram or sertraline) and Extended-Release Memantine in people with Major Depressive Disorder (MDD), run by Jeffrey Miller at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jeffrey Miller, MD (646-774-7613, HDRFstudy@nyspi.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pattern Separation Performance (time frame: At baseline (week 0) and after completing the medication trial (week 11)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07139834, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.