Use of selective serotonin reuptake inhibitors and risk of myeloid malignancy: A nationwide Danish case-control study

Preclinical and clinical studies suggest that selective serotonin reuptake inhibitors (SSRIs) can stimulate haematopoiesis by promoting proliferation and mobilization of haematopoietic stem and progenitor cells, but whether SSRI use influences myeloid malignancy risk remains unclear. We therefore conducted a nationwide case-control study using Danish healthcare registries, including 22 293 adults with incident myeloid malignancy diagnosed during 2001-2022 and 445 860 cancer-free controls matched 1:20 on age, sex and calendar year. Ever SSRI use was defined as ≥1 filled prescriptions, and long-term use as prescriptions equivalent to >3 years of use. A 6-month lag period was applied to minimize reverse causation. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusted for comorbidities, socioeconomic status and other psychotropic medications. SSRI use was not associated with increased myeloid malignancy risk compared with never use (adjusted OR, 0.98 [95% CI, 0.94-1.01] for ever use; 0.92 [95% CI, 0.86-0.97] for long-term use). No associations were observed across sex or age groups. Estimates were similar across myelodysplastic neoplasms, myeloproliferative neoplasms and acute myeloid leukaemia and individual SSRIs. These findings from a large nationwide study provide reassurance that SSRI treatment is not associated with a clinically meaningful increase in myeloid malignancy risk.