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Can SSRIs Slow Worsening of Mild Cognitive Impairment?

Information sourced from NEJM Journal Watch:

Can SSRIs Slow Worsening of Mild Cognitive Impairment?

In previously depressed individuals, long-term selective serotonin reuptake inhibitors delayed conversion from mild cognitive impairment to Alzheimer disease by about 3 years.

Controversial evidence has linked antidepressants to changes in risk for dementia owing to Alzheimer disease (AD; NEJM JW Psychiatry Jun 2017 and PLoS One 2017; 12:e0175187). Using data from 755 enrollees in a dementia study (mean age, 74), investigators studied antidepressants’ potential influence on the ongoing course of mild cognitive impairment (MCI).

Patients did not have depression at baseline; 223 had prior histories of depression: 60 were not receiving antidepressants at baseline, 116 were on selective serotonin reuptake inhibitors (SSRIs), and 47 were taking other antidepressant types (duration of treatment: 1–4 years, 52%; >4 years, 25%). At baseline, 161 participants were cognitively normal, 438 had MCI, and 156 had AD.

Past histories of depression were associated with MCI (odds ratio, 2.6) and AD (OR, 3.8). During the 2-year follow-up, prior history of depression was not associated with increased risk for conversion from MCI to AD. Compared with never-treated individuals, patients taking SSRIs had lower conversion rates, whereas patients taking other antidepressants had higher conversion rates. Patients with long-term SSRI treatment (>1610 treatment days) were less likely to convert to AD than those with shorter SSRI treatment or those receiving other antidepressants. In the first 3 years of observation, the long-term SSRI group showed less conversion than all other groups (including the never-depressed group), with a delay of AD onset of about 3 years in patients with MCI taking long-term SSRIs.


This study did not distinguish recurrent, early-onset depression from late-onset depression or examine why patients received SSRIs versus other antidepressants. SSRIs might affect amyloidogenic, neuroinflammatory, brain-derived neurotrophic factor–related, and acetylcholine regulatory processes. Clinically, these findings suggest that clinicians consider continuing long-term SSRI use, even after depressive symptoms resolve, because this treatment might substantially delay the onset of AD in patients with MCI.

Joel Yager, MD reviewing Bartels C et al. Am J Psychiatry 2017 Nov 28.


Bartels C et al. Impact of SSRI therapy on risk of conversion from mild cognitive impairment to Alzheimer’s dementia in individuals with previous depression. Am J Psychiatry 2017 Nov 28; [e-pub]. [PubMed® abstract]

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