duloxetine × Warfarin

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI). It depletes the platelet serotonin pool, impairing primary haemostasis. On warfarin, upper GI bleeding risk roughly doubles.

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

The combination is acceptable. PPI cover with pantoprazole is mandatory. Check INR at 2 and 4 weeks after starting duloxetine, then monthly. Alternative antidepressants with minimal platelet effect: mirtazapine or agomelatine.