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. 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 and AD . 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.