In Reference Palaniyappan, Insole and FerrierPalaniyappan et al's (2009) useful article, the side-effects of combination treatments neatly follow the description of each combination, but none mentions bleeding. Abnormal bleeding with selective serotonin reuptake inhibitors (SSRIs) has been studied and reviewed. One of the authors (Nick Ferrier) has written on the subject and recommended caution when prescribing SSRIs to patients at risk of gastrointestinal bleeds in particular (Reference Paton and FerrierPaton 2005).

Palaniyappan et al note that the best-evidenced combination antidepressant treatment is an SSRI plus either a noradrenergic and specific serotonergic antidepressant (NaSSA) or trazodone. Reference Meijer, Heerdink and NolenMeijer et al (2004) have demonstrated that the degree of inhibition of serotonin reuptake is associated with risk of abnormal bleeding. Furthermore, Reference de Abajo, Rodríguez and Monterode Abajo et al (1999) found that the highest association between antidepressant use and gastrointestinal bleeds occurs with trazodone (despite it being a weak serotonin reuptake inhibitor). It may be reasonable, therefore, to expect the combination of an SSRI and trazodone, through differing mechanisms, to be associated with significant abnormal bleeding.