1997, sumatriptan-treated migraineurs had significantly higher depression PCRs (22.3%) compared with non-triptan users (19.3%), a difference of 6.4% (95% confidence interval (CI) 4.6-8.4%, P < 0.001). In the year (April 1997 to March 1998) following the launch of the TELs, depression PCRs were significantly higher among patients using these compounds compared with sumatriptan-treated patients (5.1%, CI 1.8-12.0%, P < 0.05). However, after taking account of prior depression (odds ratio (OR) 6.45, 95% CI 3.63-11.43), TELs were not significantly associated with depression (OR 0.27, 95% CI 0.03-2.13). Furthermore, rates of newly diagnosed depression after treatment were similar in the two triptan groups (sumatriptan 4.2%; TELs 3.9%). Although, the TELs are being prescribed to patients with higher pre-existing rates of depression, they are not associated with subsequently increased consulting for depressive illness compared with patients taking sumatriptan. This study highlights the potential to use GPRD to test targeted hypotheses exploring pharmacovigilance issues for patients using new medicines.