Pattern separation in major depressive disorder: adding memantine to an SSRI

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This early-phase trial explores whether combining an SSRI (escitalopram or sertraline) with extended-release memantine, compared to SSRI plus placebo, improves pattern separation performance and related brain activity in the dentate gyrus as measured by fMRI, along with changes in depressive symptoms. Participants will receive open-label SSRI treatment while being randomized to memantine or placebo in a double-blind fashion. The study focuses on adults with MDD, uses neuropsychological testing and brain imaging to assess effects, and aims to clarify whether memantine adds benefit beyond SSRI therapy. Safety and eligibility criteria center on stable health, non-pregnant status, and capacity to consent.

Why it matters

Who can join: the full rules

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

Where it's running

• New York State Psychiatric Institute (NYSPI)
  New York, New York, United States Recruiting

Study contacts

• Principal investigator: Jeffrey M Miller, MD — New York State Psychiatric Institute (NYSPI)
• Study coordinator: Jeffrey Miller, MD
• Email: HDRFstudy@nyspi.columbia.edu
• Phone: 646-774-7613

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.