Combined treatment with escitalopram and memantine increases gray matter volume and cortical thickness compared to escitalopram and placebo in a pilot study of geriatric depression

Abstract

Background: Geriatric depression with subjective cognitive complaints increases the risk of Alzheimer's Disease (AD). Memantine is a cognitive enhancer used to treat AD. In a 6-month double-blind randomized placebo-controlled trial of escitalopram and memantine (ESC/MEM), ESC/MEM improved cognition at 12 month in geriatric depression (NCT01902004). We now investigated structural neuroplastic changes at 3 months.

Methods: Forty-one older depressed adults (mean age=70.43, SD=7.33, 26 female) were randomized to receive ESC/MEM or ESC/PBO. Mood scores (Hamilton Depression Rating Scale, HAMD) and high-resolution structural T1-weighted images were acquired at baseline and 3 months. Freesurfer 6.0 for image processing and General Linear Models was used to examine group differences in symmetrized percent change gray matter volume (GMV) and cortical thickness, controlling for age and intracranial volume. Nonparametric tests were used to investigate group differences in mood and subcortical volume change.

Results: Among 27 completers (ESC/MEM n = 13; ESC/PBO n = 14), 62% achieved remission (HAMD≤6) with ESC/MEM and 43% with ESC/PBO (Fisher's exact p=.45). Change in HAMD did not differ between groups (F(1,23)=0.14, p=.7). GMV and thickness increased more with ESC/MEM than with ESC/PBO in the left middle and inferior temporal lobe, right medial, and lateral orbito-frontal cortex (OFC).

Limitations: included small sample size, dropout, and the lack of cognitive data at 3 months.

Conclusions: Although significant group differences in mood improvement were not observed, ESC/MEM resulted in increased GMV and cortical thickness in several brain regions compared to placebo. Larger longitudinal clinical trials can further examine the neuroprotective effect of memantine in geriatric depression.

Conflict of interest statement

Declaration of Competing Interest Dr Lavretsky has received research grants from Allergan, NIMH, NCCIH, PCORI and the Alzheimer's Research & Prevention Foundation. The other authors report no conflicts of interest.

Copyright © 2020 Elsevier B.V. All rights reserved.

Figures

Figure 1.

Consort diagram.

Figure 2.. Between-group differences in GMV changes after three months of memantine treatment.

GMV (top panel) and cortical thickness (bottom panel) in the left inferior and middle temporal lobe and the right medial (and for GMV also the lateral OFC) cortices increased significantly more in the memantine compared to the placebo group.