Examining the Effects of Escitalopram and Memantine on Pattern Separation in Major Depressive Disorder

Plain English Summary

Pattern Separation in Major Depressive Disorder is a Phase 1 clinical trial sponsored by Jeffrey Miller studying Major Depressive Disorder (MDD). This trial investigates how escitalopram (a common depression medication) combined with either memantine or a placebo affects memory function in people with major depressive disorder. It is for adults aged 18-50 diagnosed with major depressive disorder who are not currently taking antidepressant medication. Participants will take escitalopram for 11 weeks, with the last 6 weeks involving either memantine or a placebo, and undergo brain scans and memory tests. Standard treatments for depression include various antidepressants, psychotherapy, and lifestyle changes. The trial aims to enroll 30 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 18 and 50 years old and have been diagnosed with major depressive disorder. You must have a certain level of depression severity and be willing to use effective birth control if you can become pregnant. You cannot join if you are currently taking antidepressants, are pregnant or breastfeeding, have unstable medical conditions, or have certain neurological or psychiatric conditions. Specific heart rhythm (QTc interval) and urinary conditions, as well as recent use of certain other medications, will also exclude you. This trial is studying Major Depressive Disorder (MDD), so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how well participants can distinguish between similar memories after the treatment, indicating potential improvements in a specific type of memory function affected by dep The specific primary outcome measures are: Pattern Separation Performance (At baseline (week 0) and after completing the medication trial (week 11)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial aims to address the cognitive challenges, specifically memory, that often accompany major depressive disorder, a gap not always fully addressed by current treatments. This research targets Major Depressive Disorder (MDD), where improved treatment options are needed.

Investor Insight

This Phase 1 trial, while early stage, explores novel drug combinations for a large market (MDD), with potential for improved cognitive outcomes, signaling a possible future therapeutic advancement. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific medications being tested, potential side effects, and how participation might affect your daily routine. Be prepared for regular study visits for medication, brain imaging (MRI), and cognitive assessments. Ensure you understand the commitment to using effective contraception if applicable and providing emergency contact information. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 30 participants

Interventions

• DRUG: 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: Extended-Release Memantine — 6 weeks of treatment with extended-release memantine as augmentation to ongoing escitalopram treatment
• DRUG: Placebo — 6 weeks of treatment with placebo as augmentation to ongoing escitalopram treatment

Primary Outcomes

• Pattern Separation Performance (At baseline (week 0) and after completing the medication trial (week 11))

Secondary Outcomes

• Depression Severity (At screening, baseline (week 0) and after completing the medication trial (week 11))

Full Eligibility Criteria

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

Trial Locations

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

Frequently Asked Questions

Related Conditions

• Major Depressive Disorder (MDD)
• Cognitive Impairment
• Memory Disorders
• Neuropsychiatry
• Geriatric Psychiatry (though this trial is for younger adults, memantine is used in Alzheimer's)
• Neurology
• Psychopharmacology
• Mental Health
• Anxiety Disorders
• Bipolar Disorder (as an exclusion criterion, highlighting related conditions)

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