Pattern Separation in Major Depressive Disorder

Prior treatment

• Currently taking an antidepressant medication at study enrollment
• 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)
• 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

Other illness

• Evidence of current unstable medical illness, including liver or renal impairment, or unstable cardiovascular or respiratory illness
• 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 substance use disorder other than tobacco use disorder
• 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
• Any condition or material in the body that is a contraindication for MRI procedures

Lab values

• QTc interval greater than 500 ms

Other

• Pregnant or breastfeeding at time of enrollment
• Current active suicidal ideation
• Current use of disulfiram with oral concentrate, MAOIs (including linezolid or IV methylene blue), or pimozide
• Weight that exceeds 300 lbs or inability to fit into MRI scanner
• MST LDI score greater than 0.5

• 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