Escitalopram-Memantine Combination Improves Cognitive Outcomes in Older Adults With MDD

The combination of memantine with escitalopram was linked to improved cognition in older patients with major depressive disorder.

Combination escitalopram and memantine improved cognitive and clinical outcomes in older patients with major depressive disorder (MDD) and subjective memory complaints, according to results from a study published in the American Journal of Geriatric Psychiatry.

Researchers conducted a double-blind, placebo-controlled, randomized study of 95 older adults with MDD and subjective memory complaints. Study patients were randomly assigned to receive either escitalopram plus memantine (n=48) or escitalopram plus placebo (n=47) for a total of 12 months. Participants were started on 5 mg memantine daily and 10 mg escitalopram daily, titrated to a maximum of 20 mg daily for both agents. The primary outcome measured was the change in depression severity, measured using the 24-item Hamilton Rating Scale for Depression.

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After analysis, the researchers found no significant difference in remission rates between the 2 groups at 3 and 6 months (P =.15).

In contrast, both groups saw significant improvements in 24-item Hamilton Rating Scale for Depression scores at 3, 6, and 12 months (All P <.0001), but no between-group differences were observed.

In addition, the escitalopram-memantine group showed significantly higher improvement in executive functioning and delayed recall vs the escitalopram-placebo group at 12 months (P =.01 and P =.02, respectively).

One key limitation of the study was the lack of heterogeneity in the sample.

“Our results suggest that this combination is safe and may improve symptoms of depression, anxiety and cognitive outcomes in this difficult-to-treat population,” the researchers wrote.

“Future reports will address the role of biomarkers of aging in treatment response,” they concluded.

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Lavretsky H, Laird KT, Krause-Sorio B, et al. A randomized double-blind placebo-controlled trial of combined escitalopram and memantine for older adults with major depression and subjective memory complaints [published online August 22, 2019]. Am J Geriatr Psychiatry. doi:10.1016/j.jagp.2019.08.011