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Are Antidepressants Carcinogenic? A Review of Preclinical and Clinical Studies

J Clin Psychiatry 2003;64(10):1153-1162

Background: Antidepressants are widely prescribed for mood and anxiety disorders, though reports in the oncology and epidemiology literature have suggested these agents may possess tumor initiating and/or promoting properties, raising questions about safe long-term use in patients. The author conducted a review of the preclinical and clinical literature on the connection between antidepressants and carcinogenesis.

Method: A MEDLINE search was conducted for English-language articles published from 1966 to 2002 using the search terms antidepressants, tumors, carcinogenesis, and cancer, as well as specific antidepressant names. Additional studies were ascertained through cross-references.

Results: Preclinical studies found evidence for both tumor promotion and suppression, though the majority of studies predominantly examined tricyclic antidepressants (TCAs), with 1 report suggesting that TCAs with a nitrogen atom in the central ring are genotoxic. Of 13 clinical studies, 3 found a significant increase, 4 noted a trend increase, and 6 found no increase in risk for cancer with antidepressant (mostly TCA) use. Methodologic differences could account for some of the discrepancies found in the clinical studies, while questions about the validity for humans of the preclinical models raise doubt about the significance of those findings.

Conclusion: While there is some suggestive evidence of an association between antidepressant use and cancer, the link is, at this time, questionable but deserving of further study, especially with newer agents. Clinicians should not withhold antidepressant medication when indicated, as the risks of untreated depressive and anxiety disorders exceed the as yet unsubstantiated risk of tumor formation in such patients.