Epidemiological studies in large cohorts of patients indicate that selective serotonin reuptake inhibitors may moderately increase the risk of bleeding (e.g. 1.5-3 times for upper gastrointestinal bleeding). Although the incidence of upper gastrointestinal bleeding after selective serotonin reuptake inhibitors alone may appear relatively low (estimated in 1 of 1300 patients), the risk of gastrointestinal bleeding may increase markedly when selective serotonin reuptake inhibitors are combined with non-steroidal anti-inflammatory drugs. Most at risk are the elderly and those with previous ulcers or gastrointestinal bleeding. In these patients, it is recommended to use non-selective serotonin reuptake inhibitors and in selective serotonin reuptake inhibitors + non-steroidal antiinflammatory drugs comedication to use gastroprotective agents (e.g. proton pump inhibitors). Combined use of a selective serotonin reuptake inhibitor and low-dose aspirin increases the risk of gastrointestinal bleeding 5 -7 times. Fatalities due to upper gastrointestinal bleeding after selective serotonin reuptake inhibitors alone or in combination with non-steroidal anti-inflammatory drugs occur very rarely. Mechanism of increased bleeding after selective serotonin reuptake inhibitors is not fully understood. It is assumed that depletion of serotonin from platelets due to selective serotonin reuptake inhibitors is involved. The increased upper gastrointestinal bleeding after a combined use of selective serotonin reuptake inhibitors with non-steroidal anti-inflammatory drugs might be due to addition of inhibitory effects of these drugs on platelet aggregation and a gastric mucose irritation produced by non-steroidal anti-inflammatory drugs.

        Key words: NSAIDs, bleeding, serotonin, platelets, drug interactions