Adjunct Memantine May Protect Memory in Patients With Geriatric Depression

Geriatric depression is often accompanied by cognitive problems such as memory lapses that put seniors at greater risk of developing dementia. A study published in the American Journal of Geriatric Psychiatry reports that adding memantine (an NMDA receptor antagonist used in the treatment of Alzheimer’s symptoms) to an antidepressant regimen may help improve memory problems associated with geriatric depression.

This benefit of memantine was seen in a clinical trial of 95 adults aged 60 and up who were diagnosed with major depression and who complained of memory problems. None of the adults screened positive for dementia; 13 had mild cognitive impairment (MCI).

All the participants took 10 mg to 20 mg of escitalopram daily along with either memantine (5 mg to 10 mg) or placebo capsules twice daily for six months. The researchers assessed the participants’ depression severity, cognition, and other health measures periodically over the six-month period, and again at a six month-follow up (12 months total).

Sixty-two participants completed the six-month trial period (33 in the memantine group and 29 in the placebo group) and 44 completed the 12-month assessment (23 in the memantine group and 21 in the placebo group). Overall, memantine was well-tolerated and the average number of side effects did not differ between the two treatment groups.

Though no significant cognitive differences emerged between participants taking memantine versus placebo during the six-month study period, the adults taking memantine performed better on cognitive assessments than adults taking placebo at the 12-month follow-up. At 12 months, the participants taking memantine had slightly higher cognitive test scores (their cognitive Z-scores rose from 0.02 to 0.15, while scores in adults who had taken placebo dropped from -0.04 to -0.26; Z-scores reflect how much better or worse someone performs than an average test taker). In particular, recall ability and executive functioning (the ability to make multi-step decisions) scores were much higher in adults taking memantine compared with the adults taking placebo. These improvements in cognition were independent of any changes in depression.

Lead investigator Helen Lavretsky, M.D., a professor in residence in the Department of Psychiatry at the University of California, Los Angeles, told Psychiatric News that this clinical data was also supported by MRI scans, PET scans, and genetic data collected from these adults.

Lavretsky and her colleagues also compared various mood symptoms to see if memantine might produce a stronger and/or more rapid antidepressant response when added to escitalopram. There were no differences in depression scores between the memantine and placebo groups at any time point using the Hamilton Depression Rating Scale. A secondary assessment using the Montgomery-Åsberg Depression Rating Scale revealed greater improvements in the memantine group relative to placebo starting at about four weeks until six months, but these improvements were no longer evident at 12 months.

Though Lavretsky hoped the addition of memantine might accelerate or elevate the antidepressant response, she said the memory improvements seen in these patients at 12 months were an important gain.

“It is common for medications to take longer to reach their full benefit in older patients with depression than in younger patients,” noted Charles Reynolds III, M.D., the University of Pittsburgh Medical Center Endowed Professor of Geriatric Psychiatry. “However, this study shows that given time, supplementing a standard antidepressant treatment with memantine does offer distinct advantages without significant risk.” (Reynolds, who was not involved with the study, is the editor-in-chief of the American Journal of Geriatric Psychiatry.)

Reynolds led a clinical trial in 2011 testing another Alzheimer’s medication—donepezil (a cholinesterase inhibitor)—as an add-on maintenance therapy for geriatric depression. That study suggested that donepezil could boost cognitive performance, but also increased the risk of depression recurrence.

“In a clinical setting, I would start with just the antidepressant, and then consider adding memantine if a patient has residual cognitive problems after a few months. Since the effects may be slow, it’s important to talk about medication adherence with patients and family.”

Reynolds added that doctors should also be aware of other possible factors leading to depression-related memory issues. Sleep problems, especially sleep apnea, are common in older adults and associated with poorer brain health, he noted.

Lavretsky’s study was supported by grants from the National Institute of Mental Health and the National Center for Advancing Translational Science. ■