Treatment-Resistant depression enhances risks of dementia and alzheimer's disease: A nationwide longitudinal study

Background: Previous evidence indicates late-onset depression or depression with greater severity are associated with subsequent risk of dementia or Alzheimer's disease (AD). However, whether treatment-resistant depression is associated with such risks remain elusive. Methods: Using the Taiwan Nationwide Health Insurance Research Database, 3,345 patients with newly-diagnosed major depressive disorder (MDD) and 13,380 well-matched controls were enrolled between 2002 and 2004. MDD patients were stratified according to their treatment response to adequate antidepressant trials, and all participants were followed up until the end of 2013. Those who developed dementia and AD were identified. Results: MDD patients were more likely to develop dementia and AD than controls. Difficult-to-treat patients (i.e., DTT; those who failed to respond to at least two adequate antidepressant trials) had the highest risk of developing dementia (hazard ratio [HR] = 5.19) and AD (HR 4.44), whereas easy-to-treat patients (i.e., ETT-1; those who had no prescription of antidepressants) had the lowest risk of developing dementia (HR 2.37) and AD (HR 2.59) compared with controls. Subsequent analysis demonstrated that only among patients with late-onset depression (age > 65 years), DTT patients consistently showed higher risks and faster development of dementia (HR 6.64, mean: 1.45 yr) and AD (HR 4.97, mean: 1.67 yr) than did ETT-1 patients and controls. Limitations: Subjects who have not received medical examination were not included as diagnosis were determined by ICD codes. Also, longer follow-up period might be needed for the younger group. Conclusions: Late-onset treatment-resistant depression is associated with an elevated risk of dementia and AD.