SSRIs May Slow Depressed Patients’ Progression From MCI to Alzheimer Disease

By Will Boggs MD

NEW YORK (Reuters Health) - SSRI treatment is associated with slower progression from mild cognitive impairment (MCI) to Alzheimer's dementia (AD) in individuals with a history of depression, according to results from the prospective Alzheimer's Disease Neuroimaging Initiative (ADNI).

"It is most interesting and encouraging to us that long-term SSRI treatment may delay MCI to AD progression in patients with a history of depression, which may be a chance to decrease Alzheimer’s dementia prevalence,” Dr. Anja Schneider from the German Center for Neurodegenerative Diseases, Bonn, Germany, told Reuters Health by email.

Selective serotonin reuptake inhibitors (SSRIs) appear to reduce amyloid plaque burden and cognitive impairment in animal models, but evidence from clinical studies is less conclusive.

Dr. Schneider and colleagues used data from 755 currently nondepressed ADNI participants to evaluate the impact of SSRI treatment on cerebrospinal fluid (CSF) biomarkers and progression from MCI to AD. Findings were published online November 28 in the American Journal of Psychiatry.

A baseline diagnosis of MCI was associated with a 2.6-fold higher likelihood of a history of depression, and a baseline diagnosis of AD was associated with a 3.77-fold higher likelihood, compared with the cognitively normal group. However, a history of depression was not associated with an elevated rate of conversion of MCI to AD.

Overall, the cumulative probability of progression of MCI to AD was significantly lower among patients with a history of depression who had been treated with SSRIs than among those with a history of depression who had been treated with other antidepressants. The MCI-to-AD progression rate among people treated with other antidepressants was higher than that among those with no depression or untreated depression.

In further analyses, the probability of progression was significantly lower in patients with a history of depression and long-term SSRI treatment (>1610 days, the median), compared to treatment with other antidepressants or short-term (1610 days or less) SSRI treatment.

Long-term SSRI treatment appeared to delay MCI-to-AD conversion by a mean 891 days; the mean delay with short-term SSRI treatment was 884 days.

CSF biomarker levels did not differ between people with versus those without a history of depression, and SSRI treatment had no effect on CSF amyloid-beta(1-42), tau, p-tau(181), or soluble amyloid precursor protein (sAPP)-beta levels.

“It remains to be investigated whether SSRI treatment may also be beneficial in MCI patients without previous depression,” Dr. Schneider said. “Based on our results, we would not give a general recommendation to treat MCI patients with SSRIs. Our findings still need to be validated in independent cohorts or even better by a prospective intervention trial.”

“If there are no contraindications, I would probably prefer SSRI to non-SSRI antidepressants for MCI patients with depression and start treatment early,” she said.

SOURCE: https://bit.ly/2kEpV1x

Am J Psychiatry 2017.

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