Antidepressants and Dementia Risk: Findings From a Retrospective Study on U.S. Veterans with Depression

In a nationwide retrospective study covering over two decades, researchers investigated the impact of antidepressant exposure on dementia risk among U.S. veterans diagnosed with major depressive disorder (MDD) during midlife. The study aimed to shed light on the conflicting evidence around the influence of antidepressants on the progression to Alzheimer's disease (AD) and AD-related dementias (AD/ADRD).

The study utilized data from the Veterans Affairs healthcare system, following 35,200 patients diagnosed with MDD from January 1, 2000, to June 1, 2022. Researchers employed complex inverse probability weighted (IPW) Cox models with time-varying covariates to account for fluctuations in drug treatments over time.

Surprisingly, the study found no link between exposure to antidepressants and an increased risk of developing AD/ADRD. This included the examination of specific antidepressant classes against non-exposure. Nonetheless, a notable finding was the observed reduction in AD/ADRD risk among female patients, although this was based on a smaller subset of cases.

The study's extensive sample size, focus on older veterans, and prolonged observation period provided a robust dataset. However, the cohort's relatively younger age at MDD diagnosis posed a limitation, restricting the study's capability to track a sufficiently high number of dementia cases. Moreover, the exclusion of supplemental insurance data after the age of 65, such as Medicare, might have led to under-recording of dementia diagnoses.

Researchers call for caution in interpreting the data, especially given the potential for antidepressant underutilization due to adherence challenges and side effects. They also indicate a need to further explore observed sex differences in antidepressant response, possibly related to the differential impact on microglial activation by gender.

To confirm the findings, replication in external populations with a more significant representation of female patients is advised. If validated, this study could have implications for the management of depression in midlife and the potential impact of antidepressant medication on long-term cognitive health.

The full study is available through open access at Wiley Online Library and can be found here: Antidepressants and Dementia Risk Study. Follow the link for more detailed information and access to additional supplementary materials.

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