The Antidepressant Therapy Selective Norepinephrine Reuptake Inhibitors (SNRIs) Reduces the Risk of Alzheimer’s Disease

Abstract Background Depression has been established as a risk factor for developing Alzheimer’s Disease (AD). Further, depression is a common symptom of the prodromal phase of the disease and acts as an accelerating factor for cognitive decline before and after dementia diagnosis. Based on this association, analyses of real‐world medical data were conducted to determine the impact of anti‐depressive pharmacological therapy, Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), on risk of AD diagnosis. This study aimed to determine the effect of SNRI therapy on AD incidence, as well as determining responder vs non‐responder phenotypes on demographic characteristics, comorbidity burden, and co‐treatment profile. Method A retrospective analysis was conducted using the Mariner insurance claims dataset and included patients 60 years of age and older with a diagnosis of depression. To minimize bias, a propensity score matching was conducted to adjust for age, gender, cci and comorbidities. The propensity score matched population was surveyed for a diagnosis of AD after at least 1 year of SNRI drug exposure, and different durations of SNRI therapy were analyzed. Responders were detected through sensitivity analyses based on comorbidities and drug combinations. Result The propensity score matched group included 307,671 patients exposed to SNRIs and 307,671 patients with no exposure to any antidepressant therapy. SNRI therapy was associated with a significant decrease in risk of AD diagnosis (RR [95%CI]: 0.73 [0.70–0.76]; P<.0001), with women (RR [95%CI]: 0.66 [0.63–0.70]; P<.0001) exhibiting greater risk reduction compared to men (RR [95%CI]: 0.88 [0.82–0.95]; P<.0001). Long‐term SNRI treatment (>6 years) was associated with the greatest AD risk reduction (RR [95%CI]: 0.50 [0.47–0.53]; P<.0001). Responders exhibited higher incidence of obesity and greater use of anti‐inflammatories. Conclusion SNRI therapy was associated with a significant reduction in AD risk. Furthermore, increased duration of SNRI therapy was associated with greater AD risk reduction. Responders displayed fewer comorbidities and co‐treatments although they had a higher incidence of obesity. Clinically, these findings, based on real‐world psychiatric care, provide data regarding long‐term neurological health outcomes of SNRI anti‐depressant therapy. From a mechanistic perspective, data reported herein indicate that sustaining noradrenergic function is a key pathway involved in preventing AD.