Purpose: To compare the user profiles of the two classes of drug, using the Tayside Medicines Monitoring Unit (MEMO) record-linkage database. Methods: A cohort study was carried out in the population of Tayside in Scotland. A total of 13 901 selective serotonin re-uptake inhibitor (SSRI) users and 1417 selective norepinephrine re-uptake inhibitor (SNRI) users were identified during the period of December 2000 to November 2001. A logistic regression model was used to assess the association between drug use and patients profiles and a Cox regression model was employed to examine the effect of drug use and mortality outcome. Results: Compared to SNRI patients, SSRI patients were significantly older (28.8% ≥ 60 year vs. 26.2%), more likely to be female (70.9% vs. 67.8%), had more cardiovascular disease history (10.1% vs. 8.5%), but were less deprived (9.7% in the highest deprivation category vs. 12.4%), had less digestive disease (27.9% vs. 31.0%) and less history of drug overdose hospitalisation (7.2% vs. 11.9%). SNRI patients had more drug switching than SSRI patients (62.0% for recent users, 33.2% for prevalent users vs. 39.1%, 26.1%, respectively).The age-standardised mortality rates during the follow-up period until December 2003 were 5.3% for SSRI and 5.9% for SNRI users. Conclusion: There was clear evidence that SSRI and SNRI were used in patient groups with different characteristics. This channelling sometimes favoured an improved mortality outcome and sometimes favoured a worse outcome. Overall there was no mortality difference between the two classes of drugs.