Risk of Non-Hodgkin Lymphoma in Relation to Tricyclic Antidepressant Use

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Abstract Purpose: We investigated the relationship between prior use of tricyclic antidepressants (TCA) and risk of non-Hodgkin lymphomas (NHL), both overall and for common subtypes of NHL; previous studies provided some evidence of an association with NHL, but did not assess the risk of specific subtypes of NHL, which have been shown to be etiologically diverse. Methods: We conducted a population-based matched case-control study among members of Group Health (GH), an integrated healthcare delivery system. Cases included GH members diagnosed with NHL between 1980–2011 at age ≥25 with no record of a prior cancer or of certain autoimmune conditions, who had been enrolled for ≥2 years at the reference date (date of diagnosis). Eight controls were matched to each case on age, sex, enrollment on the reference date, and length of prior enrollment at GH. Information on prior TCA use, including dose, duration, recency, and type, was ascertained from automated pharmacy data. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for NHL (and common subtypes) in relation to various patterns of TCA exposure using conditional logistic regression adjusted for confounders. Results: We identified 2,768 cases and 22,127 matched controls. We did not observe an appreciably increased risk of NHL among persons who had filled ≥2 TCA prescriptions prior to the reference date compared to those who had filled none (OR: 1.1; 95% CI: 1.0–1.2). Overall risk of NHL was associated to at most a small degree with longer-term use (OR: 1.2; 95% CI: 1.0–1.4 for ≥10 prescriptions), high-dose use (OR: 1.1; 95% CI: 0.8–1.5 for ≥50 mg or equivalent), or use that began more than 5 years prior to reference date (OR: 1.0; 95% CI: 0.9–1.2). TCA use was generally not associated with most major NHL subtypes, though longer-term TCA use was associated with increased risk of chronic lymphocytic leukemia/small lymphocytic lymphoma (OR: 1.5; 95% CI: 1.1–2.0). Conclusions: We found little evidence that TCA use increases risk of NHL, overall or for specific common subtypes of NHL.