Dementia Risk Among Patients with Major Depressive Disorder: Does Antidepressant Class Matter?

The association between the risk of dementia and different classes of antidepressants, as well as the potential influence of treatment resistance or response, remains unexplored in individuals with major depressive disorder (MDD).

Using the Taiwan National Health Insurance Research Database, 30,390 patients with MDD and 24,312 well-matched controls were enrolled between 2002 and 2004. We stratified the antidepressant-resistant depression (ART, n = 6,078) and antidepressant-responsive depression (ARP, n = 24,312) groups. Selective serotonin reuptake inhibitors (SSRIs) versus non-SSRIs, was included as a stratification factor. The risks of dementia were examined using a Cox regression model (reported as hazard ratio with 95% confidence interval).

Both the ART and ARP groups had a 5-24 fold higher risk of developing dementia than the controls. ART appeared to be associated with a higher risk of developing dementia than ARP, including any dementia (13.02 [11.08-15.31] versus 7.70 [6.63-8.94] and unspecified dementia 12.81 [10.52-15.59] versus 7.33 [6.11-8.79]). Subsequent analysis demonstrated that in the ART group, individuals who were resistant to SSRIs only (12.01 [10.02-14.40]) or both SSRIs and non-SSRIs (13.87 [11.67-16.47]) appeared to have a higher risk of developing any dementia than the ARP group (7.70 [6.63-8.94]). With the ARP as reference group, patients who were only resistant to SSRIs and those who were resistant to both SSRIs and non-SSRIs had a higher risk of developing any dementia.

In elderly patients with MDD, the risk of dementia is higher among those who are resistant to any type of antidepressant medication.