Abstract 3452: Antidepressant use and risk of central nervous system metastasis
Authors: Herr Megan , Mohile Nimish , van Wijngaarden Edwin , Brown Edward , Rich David Q. 
Published: July 2016

Abstract
CNS metastasis is the spread of a primary cancer to the CNS and occurs in up to 25% of cancer patients. Antidepressant therapy, used in 15-30% of cancer patients, affects the blood-brain barrier, potentially making patients more susceptible to CNS metastasis. This hypothesis is supported by an experimental study reporting increased CNS metastasis from breast cancer in mice receiving fluoxetine, an antidepressant in the class of selective serotonin reuptake inhibitors (SSRIs). However, no human studies have looked at this association. We conducted a case-control study to examine whether antidepressants, and specifically SSRIs, increased the relative odds of CNS metastasis.
We identified cancer patients diagnosed with breast cancer, melanoma, and non-Hodgkin lymphoma (NHL) at one academic cancer center in Rochester, NY between 2005 and 2013. We ascertained 189 patients with CNS metastasis (cases) and 945 patients without CNS metastasis (controls). Cases of CNS metastasis were identified by the ICD-9 code 198.3 secondary malignant neoplasm of brain and spinal cord. Cases and controls were classified with regard to their antidepressant use based on medical chart review. Using multivariable logistic regression, we estimated the relative odds of CNS metastasis associated with ‘any antidepressant use’ (any antidepressant irrespective of class), ‘any SSRI use’ (SSRI use, nonexclusively), and ‘exclusive SSRI use’ (only SSRI use and no other class of antidepressant), all compared to ‘no antidepressant use’. Subset analyses were planned a priori for breast cancer and melanoma; subset analyses could not be conducted for NHL due to the small sample size.
Both cases and controls had a median age of 53 years (range: 25-94 years and 15-89 years, respectively). The prevalence of ‘any antidepressant use’ was 28.6% in cases and 25.7% in controls, whereas SSRIs were used in 16.9% of cases and 15.6% of controls. Among all patients, ‘any SSRI use’ was not associated with CNS metastasis (odds ratio (OR) = 1.21; 95% confidence interval (CI) = 0.74, 1.97). However, among breast cancer patients, ‘any SSRI use’ was associated with a 1.73 times greater odds of CNS metastasis (95% CI = 0.75, 4.04). No consistent patterns of association were observed in the analyses of other cancer subsets or exposure measures.
This was the first study to examine the association between antidepressant use and CNS metastasis. We did not observe clear patterns of association which may be due in part to the small sample size in many of our analyses. However, we believe that the increased odds in the breast cancer subset warrants further investigation as this is consistent with the animal research.
Citation Format: Megan Herr, Nimish Mohile, Edwin van Wijngaarden, Edward Brown, David Q. Rich. Antidepressant use and risk of central nervous system metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3452.