Recruiting
Phase 1

Escitalopram with Memantine

Sponsor:

Jeffrey Miller

Code:

NCT07139834

Conditions

Major Depressive Disorder (MDD)

Eligibility Criteria

Sex: All

Age: 18 - 50

Healthy Volunteers: Not accepted

Interventions

SSRI (escitalopram or sertraline)

Extended-Release Memantine

Placebo

Study Details

Brief 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 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.

Conditions

Major Depressive Disorder (MDD)

Study ID

NCT07139834

Start date

Jun 1, 2026

Status verified date

Jul, 2026

Completion date

Jun 30, 2027

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 50

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • 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

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: SSRI + Memantine

placebo comparator: SSRI + Placebo

Interventions

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.

Extended-Release Memantine

6 weeks of treatment with extended-release memantine as augmentation to ongoing escitalopram treatment

Placebo

6 weeks of treatment with placebo as augmentation to ongoing escitalopram treatment

Primary outcome measure

  • Pattern Separation Performance [ Time Frame: At baseline (week 0) and after completing the medication trial (week 11) ]

Central Contacts and Locations

Central contacts

Gabriella F Restifo-Bernstein, BA

646-774-8138gabriella.restifo@nyspi.columbia.edu

Jeffrey M Miller, MD

646-774-7613jeffrey.miller@nyspi.columbia.edu

Locations

New York State Psychiatric Institute (NYSPI)

Recruiting

New York, New York, United States, 10032

Contacts

Jeffrey M Miller, MD

646-774-7613jeffrey.miller@nyspi.columbia.edu

Gabriella F Restifo-Bernstein, BA

646-774-8138gabriella.restifo@nyspi.columbia.edu

Principal Investigator:

Jeffrey M Miller, MD

More Information

Sponsor

Jeffrey Miller

Last update posted

Jul 14, 2026

Last verified

Jul, 2026

Keywords

  • Depression
  • Major depressive disorder
  • MDD
  • Pattern separation
  • Memantine

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-12. This information was provided to ClinicalTrials.gov by Jeffrey Miller on 2026-07-14.