There is an ongoing discussion on the relation between risk of violent behaviour and the use of antidepressants. The claim that the use of antidepressants can cause violent behaviour would gain credibility if a positive association between the two could be established. The objective of this study is to evaluate the relationship between homicide, suicide and homicide-suicide rates and the rates of antidepressant use by gender and age group. Nationwide data from the Netherlands on antidepressant prescriptions (ADs, SSRI and venlafaxine) and lethal violence were analysed over the 15-year period from 1994 to 2008. The findings indicated a significant negative association between lethal violence (homicide and suicide) and prescription of antidepressants in the Netherlands, indicating that in a period in which the exposure of the Dutch population to antidepressants increased, rates of lethal violence decreased. These data lend no support for an important role of antidepressant use in lethal violence.