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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
30
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.
6 weeks of treatment with extended-release memantine as augmentation to ongoing escitalopram treatment
6 weeks of treatment with placebo as augmentation to ongoing escitalopram treatment
New York State Psychiatric Institute (NYSPI)
New York, New York, United States
Pattern Separation Performance
Participants will complete a pattern separation task
Time frame: At baseline (week 0) and after completing the medication trial (week 11)
Depression Severity
Depression severity will be assessed using the Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: At screening, baseline (week 0) and after completing the medication trial (week 11)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.