Suicide

In the period under study, the suicide rate in the Netherlands decreased from 10.26 in 1994 to 8.77 per 100,000 in 2008. This decrease seems to be a continuation of a long-term decline since the 1980s, in which the suicide rate was approximately 15 per 100,000 (van Hemert and de Kruif 2009).

The increase in the use of antidepressants is associated with a decrease in suicide rate. The association is strong; the changes in the use of antidepressants can account for 54% of the variation in suicide rate. These findings are in line with previous research. When examining the younger subgroups that might be especially at risk, the negative association between prescription of AD and SSRI ± Ve on the one hand and suicide rates on the other is confirmed. The increase in suicide risk in children and adolescents found in previous research is largely based on an increase in suicidal ideation and nonfatal suicidal behaviour in studies comparing efficacy of AD versus placebo (Hammad et al. 2006; Stone et al. 2009). The risk factors for nonfatal suicidal behaviour (e.g. younger and female) and completed suicide (e.g. older and male) are not the same: An increase in suicidal ideation and nonfatal suicidal behaviour does not necessarily reflect an increase in completed suicide (Baldessarini et al. 2006).

Homicide and homicide–suicide

To our knowledge we are the first to report on the relation between lethal violence directed towards others and the use of antidepressants over a long period of time (15 years). We found a significant negative association between homicide and prescription of AD and SSRI ± Ve in the Netherlands, indicating that in a period in which the exposure of the Dutch population to antidepressants increased, the homicide rates decreased. As is the case for suicide, the association is strong, changes in the use of antidepressants can account for 65% of the variation in homicide rates. These data lend no support for an important role of antidepressant use in homicide. With regard to the subgroup analysis, the younger male groups are of primary interest. Here, the same negative associations are found.

These findings are in contrast with a recent study based on reported adverse events in the Adverse Event Reporting System of the FDA from 2004 to 2009, which concludes that “acts of violence towards others are a genuine and serious adverse drug event associated with a relatively small group of drugs [including] antidepressants with serotonergic effects” (Moore et al. 2011). In this study, violent thoughts and acts towards others were significantly more reported than would be expected by chance. There are several ways to explain these findings. Publicity about the possibility of violent behaviour as an adverse event of a class of drugs will raise the number of reports. In addition, one has to take the reasons for prescribing antidepressants into account. Despair can be one reason to consider such treatment. At the same time, despair is a risk factor for violent thoughts and behaviour. Further, problems with impulse control may be a reason to consider antidepressant treatment. Recently, the first placebo-controlled trial was published in which efficacy was shown of an SSRI (fluoxetine) in conjunction with cognitive behavioural therapy in a group of perpetrators of domestic violence. Measures of anger and physical aggression were reduced (George et al. 2011). These findings suggest that antidepressant treatment might actually help patients to control their violent thoughts and behaviour. Earlier research has shown that aggressive behaviour both to oneself or outwards to others is associated with serotonergic dysfunction. Enhancement of serotonergic function by prescription of an antidepressant might be an appropriate thing to do and explain of the negative associations found in the present study (Walsh and Dinan 2001).

There appears to be a striking parallel with the use of antidepressants and suicide. However, suicide has a more direct relationship with depression and the use of antidepressants than homicide. Antidepressants are not generally prescribed to homicidal persons. The negative association found between the use of antidepressants and homicide is probably more strongly influenced by other factors.

Limitations

Detailed information on individuals who committed a form of lethal violence was not available. Future research should attempt to overcome this difficulty by obtaining additional information on autopsy reports from suicide decedents, an approach used in previous studies (Barber et al. 2008). In addition, detailed data per type of antidepressant per age and gender category were only available for the period 2002–2008. By applying average fractions of users per antidepressants, we were able to calculate the total number of users by gender and age group for the period 1996–2001. This approach, however, is based on the assumption that the fraction of users per antidepressants remains fairly stable over time. This assumption might have caused a wrongful estimation of actual use per age and gender category.