Anitdepressant exposure and risk of Cryptogenic Fibrosing Alveolitis (CFA): A case-control study using the General Practice Research Database (GPRD)

In a recent pilot study of 141 cases and 246 controls we have identified an association between exposure to tricyclic antidepressants, and in particular imipramine or dothiepin, and CFA. These associations preceded the development of disease by at least 5 years. In order to investigate these findings further in another dataset we have now completed a case-control study using the GPRD. Cases were defined if a diagnosis of CFA was recorded anywhere in the patients records, and up to six controls were individually matched to each case by age, sex and general practice. Cases and controls with a diagnosis of any connective tissue disease were excluded. Data were available for 890 cases and 5884 controls. The median age of cases at diagnosis was 71 years and 553 (62%) were male. More cases than controls had been exposed to all the major categories of antidepressants (table). The size of these effects were generally small and there was no evidence of interaction with either sex or quartile of age. Drug group Odds ratio 95%CI p value Any antidepressant 1.52 1.24 to 1.86 0.0001 Tricyclic 1.44 1.16 to 1.78 0.0011 SSRIs 1.85 1.25 to 2.74 0.0035 The effect of exposure to any antidepressant was present even five years before disease diagnosis (Odds Ratio 1.41, 95%CI 0.97 to 2.06). For individual antidepressants the exposure levels were low, and the only notable associations were with amitriptyline (OR 1.62, 95%CI 1.16 to 2.27) and paroxetine (OR 1.86, 95%CI 0.95 to 3.62). In summary there is an association between antidepressant depressant exposure and CFA which appears to predate the diagnosis of disease by at least five years.