Associations between antidepressant use and the risk of dementia or cognitive impairment
| Study | Study population | Results |
|---|---|---|
| Goveas et al., 2012 [89] | 6,998 women aged 65–79 without dementia | Antidepressant use is associated with a 70% increased risk of MCI over 7.5 years; risk similar for TCAs and SSRIs |
| Brodrick and Mathys, 2016 [88] | 605 patients with MDD aged > 65 | Antidepressant treatment for > 5 years is associated with a 4-fold decrease in dementia risk |
| Lee et al., 2016 [90] | 5,394 patients with MDD and subsequent dementia; 5,232 patients with MDD without dementia | All classes of antidepressants except TCAs are associated with a 1.5- to 2.5-fold increase in dementia risk |
| Jacob et al., 2017 [91] | 55,950 patients with MDD without dementia aged 60–80 | Antidepressant use protective against dementia (hazard ratio 0.8–0.9) only in patients with moderate or severe MDD |
| Lee et al., 2017 [92] | 1,774 patients with migraine and subsequent dementia and 1,774 patients with migraine and no dementia | SSRIs protective against dementia (hazard ratio 0.6); no change in risk with TCAs; increased risk with newer antidepressants (hazard ratio 4.2) |
| Then et al., 2017 [93] | 5,819 patients receiving antidepressants and 23,276 matched controls | All classes of antidepressants are associated with a 2- to 4-fold increase in dementia risk; a greater increase is seen in patients with diagnoses other than MDD |
| Bartels et al., 2018 [87] | 755 currently non-depressed patients with MCI | In MCI patients with a past history of MDD, > 4 years of SSRI treatment delayed progression to AD; no such effect for other antidepressants |
| Heath et al., 2018 [94] | 3,059 adults aged > 65 without dementia | Paroxetine, but not other antidepressants, associated with a significant increase in dementia risk over > 7 years |
| Heser et al., 2018 [95] | 3,239 elderly patients in primary care without dementia | Antidepressant use associated with a 1.5-fold increase in dementia risk over 12 years; effect significant only for certain drugs in subgroup analyses |
| Brauer et al., 2019 [96] | 4,596 users of trazodone and 22,980 users of other antidepressants | Trazodone is associated with a 1.8-fold increase in dementia risk compared to other antidepressants |
| Kodesh et al., 2019 [97] | 71,515 adults aged > 60 without dementia | Antidepressant monotherapy associated with a 3- to 4-fold increase in dementia risk |
| Kostev et al., 2019 [98] | 20,215 patients with MDD aged 70–90 | Reduced risk of dementia with fluoxetine, venlafaxine, and duloxetine compared to citalopram over 10 years |
| Lin et al., 2020 [99] | 550,230 patients aged > 50 receiving antidepressants with or without hypnotics and with no history of dementia | Both antidepressant monotherapy and combined antidepressant/hypnotic therapy are associated with a 2-fold increase in dementia risk; the possible protective effect of antidepressant monotherapy (hazard ratio 0.4) in the subgroup with MDD |
| Su et al., 2020 [100] | 563,918 patients with MDD aged > 60 in the period 1998–2013 | No evidence of increased or decreased risk of dementia with antidepressant use |
| Babulal et al., 2022 [101] | 8,168 participants recruited from 37 United States Alzheimer’s Disease Centers | Untreated MDD is associated with a 77% risk of AD; MDD treated with antidepressants is associated with a 45% risk of AD over those without MDD |
| Tournier et al., 2022 [102] | Healthcare claim data on all adults aged > 50 in the period 2006–2017 | No evidence of increased or decreased risk of dementia with antidepressant use |
| Yang et al., 2023 [103] | 354,313 participants aged 50–70 from the UK Biobank | MDD is associated with a 51% increase in dementia risk; antidepressant treatment lowered this risk (hazard ratio 0.7) |
MCI: mild cognitive impairment
