OBJECTIVE: To compare the temporal changes in suicide rate among patients treated with antidepressants with the change in suicide rate among persons who have not been treated with antidepressants during 1995-1999. METHOD: In a historic prospective national pharmacoepidemiological register linkage study by using four Danish registers we included 438,625 patients who had purchased antidepressants, and compared them with 1,199,057 population based control persons. The annual rate of suicide was estimated using Poisson regression analyses. RESULTS: The suicide rate decreased for persons treated with antidepressants as well as for persons not treated with antidepressants. The proportion of persons, who committed suicide and who had not been treated with antidepressants decreased. The reduction in suicide rate was more pronounced among persons treated with SSRIs or older antidepressants than among persons not treated with antidepressants. CONCLUSION: Several factors contribute to the decreasing suicide rate. The most pronounced decrease in suicide rate was found among persons treated with antidepressants.